case study on lung cancer slideshare

• Biomarker-Driven Lung Cancer
• HER2-Positive Breast Cancer
• Chronic Lymphocytic Leukemia
• Small Cell Lung Cancer
• Renal Cell Carcinoma

• CONFERENCES
• PUBLICATIONS

Case 1: 72-Year-Old Woman With Small Cell Lung Cancer

EP: 1 . Case 1: 72-Year-Old Woman With Small Cell Lung Cancer

Ep: 2 . case 1: extensive-stage small cell lung cancer background, ep: 3 . case 1: impower133 trial in small cell lung cancer, ep: 4 . case 1: caspian trial in extensive-stage small cell lung cancer, ep: 5 . case 1: biomarkers in small cell lung cancer, ep: 6 . case 1: small cell lung cancer in the era of immunotherapy.

EP: 7 . Case 2: 67-Year-Old Woman With EGFR+ Non–Small Cell Lung Cancer

Ep: 8 . case 2: biomarker testing for non–small cell lung cancer, ep: 9 . case 2: egfr-positive non–small cell lung cancer, ep: 10 . case 2: flaura study for egfr+ metastatic nsclc, ep: 11 . case 2: egfr+ nsclc combination therapies.

EP: 12 . Case 2: Treatment After Progression of EGFR+ NSCLC

EP: 13 . Case 3: 63-Year-Old Man With Unresectable Stage IIIA NSCLC

Ep: 14 . case 3: molecular testing in stage iii nsclc, ep: 15 . case 3: chemoradiation for stage iii nsclc, ep: 16 . case 3: pacific trial in unresectable stage iii nsclc, ep: 17 . case 3: standard of care in unresectable stage iii nsclc, ep: 18 . case 3: management of immune-related toxicities in stage iii nsclc.

Mark Socinski, MD: Thank you for joining us for this Targeted Oncology ™ Virtual Tumor Board ® focused on advanced lung cancer. In today’s presentations my colleagues and I will review three clinical cases. We will discuss an individualized approach to treatment for each patient, and we’ll review key clinical trial data that impact our decisions. I’m Dr. Mark Socinski from the AdventHealth cancer institute in Orlando, Florida. Today I’m joined by Dr Ed Kim, a medical oncologist from the Levine Cancer Institute in Charlotte, North Carolina; Dr Brendon Stiles, who is a thoracic surgeon from the Weill Cornell Medical Center in New York ; and Dr Tim Kruser, radiation oncologist from Northwestern Medicine Feinberg School of Medicine in Chicago. Thank you all for joining me today. We’re going to move to the first case, which is a case of small cell lung cancer. I’m going to ask Dr Kim to do the presentation.

Edward Kim, MD: Thanks, Mark. It’s my pleasure to walk us through the first case, which is small cell lung cancer. This is a case with a 72-year-old woman who presents with shortness of breath, a productive cough, chest pain, some fatigue, anorexia, a recent 18-pound weight loss, and a history of hypertension. She is a schoolteacher and has a 45-pack-a-year smoking history; she is currently a smoker. She is married, has 2 kids, and has a grandchild on the way. On physical exam she had some dullness to percussion with some decreased-breath sounds, and the chest x-ray shows a left hilar mass and a 5.4-cm left upper-lobe mass. CT scan reveals a hilar mass with a bilateral mediastinal extension. Negative for distant metastatic disease. PET scan shows activity in the left upper-lobe mass with supraclavicular nodal areas and liver lesions, and there are no metastases in the brain on MRI. The interventional radiographic test biopsy for liver reveals small cell, and her PS is 1. Right now we do have a patient who has extensive-stage small cell lung cancer. Unfortunately, it’s what we found. It’s very common to see this with liver metastases.

Transcript edited for clarity.

FDA Approval Marks Amivantamab's Milestone in EGFR+ NSCLC

In this episode, Joshua K. Sabari, MD, discusses the FDA approval of amivantamab plus chemotherapy as a first-line treatment for patients with EGFR exon 20 insertion mutation-positive non-small cell lung cancer.

Understanding ADC Mechanism of Action Enhances Personalized Medicine in NSCLC

There is currently 1 FDA-approved antibody-drug conjugate available for patients with non-small cell lung cancer, and several more potentially coming down the pike.

Lisberg Discusses Dato-DXd's Role in Advanced Lung Cancer Care

In this episode of Targeted Talks, Aaron Lisberg, MD, discusses results from the phase 3 TROPION-Lung01 study of datopotamab in advanced or metastatic non–small cell lung cancer.

Multiple Resistance Mechanisms Thwart Efficacy for Third-Generation TKIs in NSCLC

An important clinical strategy that focuses on improved frontline EGFR TKI regimens may help combat acquired EGFR TKI resistance and further streamline treatment options in subsequent lines, according to Balazs Halmos, MD.

Repotrectinib Elicits an Intracranial Response in ROS1+ Advanced NSCLC

During a Case-Based Roundtable® event, Christine, Bestvina, MD, discussed the intracranial responses to repotrectinib for patients with ROS1-psotive non–small cell lung cancer in the first article of a 2-part series.

2 Commerce Drive Cranbury, NJ 08512

609-716-7777

Log in using your username and password

• Search More Search for this keyword Advanced search
• Latest content
• Current issue
• Hosted content
• BMJ Journals More You are viewing from: Google Indexer

You are here

• Volume 64, Issue 7
• A case of small cell lung cancer treated with chemoradiotherapy followed by photodynamic therapy
• Article Text
• Article info
• Citation Tools
• Rapid Responses
• Article metrics

• Department of Internal Medicine; College of Medicine, Chungnam National University Hospital and Cancer Research Institute, Jungku, Daejeon, South Korea
• Professor J O Kim, Department of Internal Medicine, Chungnam National University Hospital and Cancer Research Institute, 640 Daesadong, Jungku, Daejeon 301-721, South Korea; jokim{at}cnu.ac.kr

Here, we present the case of a 51-year-old man with limited-stage small cell lung cancer (LS-SCLC) who received concurrent chemoradiotherapy and photodynamic therapy (PDT). The patient was diagnosed as having LS-SCLC with an endobronchial mass in the left main bronchus. Following concurrent chemoradiotherapy, a mass remaining in the left lingular division was treated with PDT. Clinical and histological data indicate that the patient has remained in complete response for 2 years without further treatment. This patient represents a rare case of complete response in LS-SCLC treated with PDT.

https://doi.org/10.1136/thx.2008.112912

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Currently, patients with small cell lung cancer (SCLC) are treated with chemotherapy with or without thoracic radiotherapy. Radiation therapy is generally accepted as an essential component of limited-stage SCLC (LS-SCLC). However, the local failure rate after chemotherapy and radiotherapy remains high, ranging from 30% to 70%. 1 More effective means are needed to decrease the local recurrence rate.

Endobronchial photodynamic therapy (PDT) is used to treat patients who have central-type lung cancer, with the objective of palliation in advanced cases and curative intent in patients with early-stage disease. 2 3 Furukawa et al reported that PDT resulted in a complete response (CR) rate of 92.8% in patients with lesions of <1.0 cm; recurrences after a CR were seen in 9 of 77 lesions (11.7%) <1.0 cm. 4 When the extent of the tumour and the depth of the bronchogenic carcinoma have been evaluated, PDT can be an effective local treatment modality. 4

A few studies have described the treatment of SCLC using PDT. Moghissi et al 5 reported that 10 of 100 patients with advanced SCLC underwent PDT for palliation. Kato et al 6 and Okunaka et al 7 evaluated the effectiveness of PDT in the treatment of early-stage SCLC. However, none of these studies detailed a single case of SCLC treated with PDT.

Here, we present a case in which PDT was used with curative intent in a patient having endobronchial cancer, following standard treatment for SCLC and in addition to concurrent chemotherapy and radiotherapy.

CASE REPORT

A 51-year-old man presented to our clinic with a 6-month history of worsening dyspnoea on exertion. His symptoms included a nearly constant dry cough, diminished appetite without weight loss, and fatigue. He had previously been diagnosed as having diabetes mellitus with an uncontrolled glucose level and hypertension. The patient was a smoker with a ⩾40 pack-per-year history. The Eastern Cooperative Oncology Group performance status was grade 1.

The patient had undergone testing at an outside facility because of his symptoms; a plain chest x ray revealed opacity in the left lung field ( fig 1A ). As a result, the patient was diagnosed with pneumonia and treated with antibiotics. Despite antibiotic treatment, the resolution of pneumonic consolidation was delayed. Thus, the patient was referred to our hospital. Chest CT revealed an endobronchial protruding mass in the distal left main bronchus (LMB) with a near total collapse of the left lung and a small granuloma in the posterior segment of the right upper lobe ( fig 1B ). No evidence of mediastinal nodal disease or a metastatic focus was detected. Bronchoscopic examination showed functional vocal cords and a pedunculated mass in the LMB ( fig 1C ). Bronchoscopic washing and biopsies failed to demonstrate a specific cell type. A rigid bronchoscopic biopsy was performed, and the pathological examination confirmed the presence of small cell carcinoma based on immunostaining for CD56, synaptophysin, chromogranin and leucocyte common antigen (LCA) using the initial paraffin-embedded biopsy specimen. The results were consistent with SCLC. CT of the brain was normal. Therefore, the patient was diagnosed with LS-SCLC.

• Download figure
• Open in new tab
• Download powerpoint

Summary from the initial diagnostic investigation to last follow-up (A–C) Initial diagnostic investigation on June 2006. (D–F) Response evaluation after chemoradiotherapy in October 2006. (G and H) Positron emission tomography (PET)–CT without increased glucose uptake in October 2007. (I) There is no evidence of recurrence in December 2008.

Chemotherapy with cisplatin and irinotecan was initiated, but the chemotherapeutic regimen was changed to cisplatin and etoposide (EP) after one cycle due to grade 4 diarrhoea. Concurrent with the second and third cycles of EP, the total dose of thoracic radiation therapy was 45.6 Gy in 38 fractions (120 cGy per fraction). Treatment was given twice daily, at least 6 h apart, on weekdays. Thoracic radiation therapy was delivered with 6–10 MV photons using custom-made blocks. With re-expansion of the lung on plain chest x ray ( fig 1D ), the patient’s dyspnoea was found to be greatly improved. Post-treatment chest CT showed that the endobronchial protruding mass in the distal LMB was noticeably smaller, with a residual small soft tissue nodule in the left upper lobe ( fig 1E ). Bronchoscopy revealed a pedunculated mass in the orifice of the lingular division ( fig 1F ). To evaluate the size of the tumour and identify any unknown synchronous cancer, autofluorescence bronchoscopy was performed. We applied PDT to remove the remaining tumour completely, because high dose rate brachytherapy and stereotactic radiation techniques were not available in our hospital. The remaining tumour was treated with PDT after wire basket removal of the pedunculated mass via flexible bronchoscopy. A 2.5 mg/kg dose of haematoporphyrin derivate (Photogem, Moscow Institute of High Chemical Technologies, Russia) was administered intravenously 48 h before irradiation. Using a diode laser (wavelength = 630 nm; Biolitec, Jena, Germany), a light with a 3 cm cylindrical diffuser was introduced through the working channel of an autofluorescence fibreoptic bronchoscope. Illumination was carried out in the left second carina and orifice of the lingular division. The light dose was 100 J/cm. Bronchoscopy followed PDT for debridement and detection of PDT-related complications. No immediate complications occurred.

The complete disappearance of the tumour was confirmed pathologically by subsequent bronchoscopic biopsy and radiologically by chest CT after 4 weeks. No evidence of recurrence was observed from October 2006 to December 2008. One year after PDT, combined positron emission tomography (PET) and CT revealed no metabolic evidence of recurrence. Two years after PDT, chest CT and bronchoscopy demonstrated a complete response in this patient ( fig 1G,H ). The patient refused prophylactic cranial irradiation.

PDT as a local therapeutic modality often results in a CR of centrally located early-stage lung cancer. Kato et al 3 reported that PDT resulted in a CR in about 94% of patients with centrally located early lung cancer (squamous cell type) with a limited longitudinal extent (<1 cm). Moghissi et al 5 suggested that the benefits of PDT did not differ between patients with SCLC and non-small cell lung cancer (NSCLC); however, patients with SCLC may be deprived of PDT because SCLC grows rapidly and spreads to other organs earlier than NSCLC.

A combined modality consisting of thoracic radiotherapy and systemic chemotherapy is widely accepted as the standard treatment for LS-SCLC. For cases in which a tumour remains after standard treatment, clinicians should consider additional treatment modalities, including pneumonectomy, sleeve lobectomy or intraluminal brachytherapy. In this study, we had to consider the specific features of the tumour, which was located in the bronchial mucosa without invasion into the cartilaginous layer. Although the adverse effects of PDT include photosensitivity skin reaction (sunburn) in 5–28% of cases, respiratory complications in 0–18% and non-foetal haemoptysis in 0–7.8%, PDT is a safe method. 8

To reduce the local recurrence rate after PDT, both the extent and the depth of an endobronchial tumour must be known. Autofluorescence bronchoscopy and endobronchial ultrasonography (EBUS) may be useful as additional examination methods. 9 Miyazu et al 10 demonstrated that the depth of tumour invasion estimated by EBUS was accurate based on histological findings after surgical resection.

According to the guidelines released in 2003 concerning early-stage NSCLC, PDT should be considered as a treatment option in early superficial squamous cell carcinoma, especially for inoperable cases. 11 Regarding the extent and depth of an endobronchial lesion, PDT may be an effective treatment for superficial airway lesions ⩽1 cm in length, despite a diagnosis of SCLC. In this case, we applied PDT without confirming the depth of the lesion and without confirming that viable tumour remained after chemotherapy and radiotherapy, although radiological findings were highly suggestive of viable tumour. This case is the first report of the non-recurrence of SCLC.

This case suggests that PDT can be effectively used with curative intent.

• Brenner M ,
• Okunaka T ,
• Shimatani H ,
• Furukawa K ,
• Moghissi K ,
• Stringer M ,
• Miyazawa T ,
• Kurimoto N ,
• Mathur PN ,
• Sutedja T ,

Competing interests: None.

Patient consent: Obtained.

Read the full text or download the PDF:

Got any suggestions?

We want to hear from you! Send us a message and help improve Slidesgo

Top searches

Trending searches

34 templates

32 templates

31 templates

28 templates

16 templates

35 templates

Lung Cancer Case Study

Lung cancer case study presentation, premium google slides theme and powerpoint template.

Did you know that lung cancer is one of the most common cancers in the world? It affects both men and women and, apart from smoking, there can be other causes, such as: exposure to radon gas and carcinogenic substances or exposure to tobacco smoke. To talk about a clinical case of lung cancer we have designed this template full of illustrations of this organ. We have also added various images to help illustrate the information.

Features of this template

• 100% editable and easy to modify
• 31 different slides to impress your audience
• Contains easy-to-edit graphics such as graphs, maps, tables, timelines and mockups
• Includes 500+ icons and Flaticon’s extension for customizing your slides
• Designed to be used in Google Slides and Microsoft PowerPoint
• 16:9 widescreen format suitable for all types of screens
• Includes information about fonts, colors, and credits of the resources used

What are the benefits of having a Premium account?

What Premium plans do you have?

What can I do to have unlimited downloads?

Don’t want to attribute Slidesgo?

Gain access to over 22500 templates & presentations with premium from 1.67€/month.

Are you already Premium? Log in

Related posts on our blog

How to Add, Duplicate, Move, Delete or Hide Slides in Google Slides

How to Change Layouts in PowerPoint

How to Change the Slide Size in Google Slides

Related presentations.

Premium template

Unlock this template and gain unlimited access

• Open access
• Published: 08 April 2024

Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study

• Chao Mei 1 ,
• Tian Wang 2 ,
• Baoli Xu 1 ,
• Sanlan Wu 1 ,
• Xuelin Zhang 3 ,
• Yongning Lv 1 ,
• Yu Zhang 1 ,
• Zhaoqian Liu 4 &
• Weijing Gong 1 , 5  

BMC Pulmonary Medicine volume  24 , Article number:  167 ( 2024 ) Cite this article

132 Accesses

Metrics details

Cyclin D1 ( CCND1 ) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer.

This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations.

The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057–2.912, P  = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P  = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P  = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276–8.765, P  = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025–1.897, P  = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088–3.152, P  = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015–2.359, P  = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017–4.052, P  = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083–6.336, P  = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism.

This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

Peer Review reports

Lung cancer is a prevalent disease that seriously endangers global public health [ 1 , 2 , 3 , 4 ]. According to statistics, there were about 2.20 million newly-diagnosed lung cancer cases and 1.79 million mortalities worldwide every year [ 4 , 5 ]. Lung cancer accounts for more than 20% of cancer-related deaths worldwide, surpassing the combined mortality rates of prostate, breast, and colon cancers [ 1 , 6 , 7 , 8 ]. Despite the progress made in targeted therapy and immunotherapy in the recent decades, platinum-based chemotherapy remains the most widely used treatment option in clinical practice [ 9 , 10 , 11 , 12 ]. However, due to individual variations in sensitivity, only a subset of patients benefits from this treatment [ 13 ]. Given the potential toxic reactions, it is urgent to discover reliable predictive biomarkers to predict the prognosis, therapeutic efficacy and toxicity of lung cancer patients, which is crucial for promoting personalized medicine and enhancing therapeutic outcomes [ 14 , 15 , 16 ].

Cyclins D1 ( CCND1 ) plays a vital role in cell cycle regulation which mediates the G1 to S phase transition [ 17 , 18 , 19 ]. It also has a fundamental involvement in human cancer progression, including cell proliferation, transcription, chromosome duplication and stability, DNA damage response, metabolism, tumor migration and invasion [ 17 , 20 , 21 ]. Multiple clinical studies demonstrated that dysregulation of CCND1 is associated with poor prognosis and platinum-based chemotherapy response in various human cancers, highlighting its potential as a tumor predictive biomarker [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].

Single nucleotide polymorphisms (SNPs) refer to DNA sequence polymorphisms caused by single nucleotide variation at the genomic level, accounting for over 90% of all known polymorphisms [ 33 , 34 , 35 ]. Cyclins D1 is the second most frequently amplified locus in human solid tumors [ 36 , 37 ]. The association between CCND1 A870G (rs9344) polymorphism and cancer risk has been previously investigated in lung cancer [ 38 , 39 , 40 , 41 , 42 , 43 ]. However, due to the limited number of studies and sample size, the exact role of CCND1 polymorphism in predicting lung cancer risk remains unclear. Only few studies have been conducted to investigate the correlation between CCND1 rs9344 and platinum-based chemotherapy response in lung cancer.

This study aimed to investigate the association of CCND1 rs9344 with cancer susceptibility, platinum-based chemotherapy, toxicity and overall survival of patients with lung cancer by performing hospital-based case-control study. Additionally, a meta-analysis was conducted using 5432 cases and 6452 control samples to evaluate the association between CCND1 rs9344 polymorphism and lung cancer risk. The results may provide evidence in support of the potential utilization of CCND1 rs9344 as a predictive biomarker for prognosis and chemotherapy sensitivity in Chinese patients with lung cancer in certain conditions.

Study design

During November 2011 to May 2013, 498 patients with primary lung cancer (diagnosed by cytology or histology) were consecutively recruited at Xiangya Hospital and the Affiliated Cancer Hospital of Central South University in Changsha, Hunan Province, China. During the same period, 213 healthy controls were collected from the physical examination center of Xiangya Hospital of Central South University. This study was approved by the Ethics Committee of Xiangya School of Medicine, Central South University (registration number: CTXY-110008-2), and all subjects enrolled have signed the informed consent.

Participants

All patients had been histologically or cytologically confirmed to have primary lung cancer. Subjects who were pregnant, lactating, had active infections, symptomatic brain or leptomeningeal metastases, or other previous or concurrent malignancies were excluded from the study. Among them, 467 patients were enrolled in the platinum-based chemotherapy response study. The inclusion criteria were as follows: (1) They were not administered radiotherapy and/or biological therapy prior to or during chemotherapy; (2) they received at least two cycles of platinum-based chemotherapy; (3) they underwent full follow-up (to March 2017); (4) tumors were assessed before and during treatment using the same imaging methods (Supplementary Table 1 ). Platinum-based chemotherapy regimens include pemetrexed + platinum (PP), gemcitabine + platinum (GP), paclitaxel + platinum (TP), docetaxel + platinum (DP), etoposide + platinum (EP), and other platinum-based chemotherapy regimens (irinotecan + platinum, navibine + platinum). In the case of the healthy controls, individuals with a smoking history, a history of lung ailments, or those engaged in high-risk occupations such as chemical, construction, asbestos, and coal mining work were excluded.

The endpoints of the study were as follows: chemotherapy response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and categorized as responders (complete response: CR, partial response: PR) or non-responders (stable disease: SD and progressive disease: PD). Two professional radiologists independently evaluated the CT scans of lung cancer patients before and after chemotherapy to assess the treatment effectiveness after two cycles of therapy. In case of disagreement, a third radiologist was consulted. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria 3.0 during the first two cycles of chemotherapy regimen. Grade 3 or 4 toxicity was defined as severe toxicity. Severe gastrointestinal toxicity was grade 3 or 4 nausea and vomiting. Severe hematological toxicity included grade 3 or 4 hypochromia, leukopenia, neutropenia and thrombocytopenia. Patients who experienced any type of the grade 3 or 4 toxicities described above were defined as suffering severe overall toxicity.

For the lung caner patients, age, sex, smoking status, stage, histological type, and chemotherapy regimens were collected. For the healthy controls, age, sex and smoking status were collected. The above factors age, sex, smoking status, stage, histological type, and chemotherapy regimens were considered as covaraites in this study.

DNA extraction and genotyping analysis

Venous blood DNA was extracted using the Genomic DNA Purification Kit (Promega, Madison, WI, USA). CCND1 rs9344 was genotyped using the Sequenom MassARRAY System (Sequenom, San Diego, CA, USA).

Study selection and data extraction criteria of meta-analysis

The Pubmed, Embase and Cochrane databases were utilized to identify original studies examing the association between CCND1 rs9344 and lung cancer susceptibility (up to March 29, 2023). The search formula was: “CCND1 or Cyclin D1” and “genetic polymorphism or polymorphisms or variant or rs9344” and “lung cancer”. Included studies had to be original case-control studies with detailed CCND1 rs9344 genotype frequencies or available data. The qualities of selected studies were independently assessed and identified by two researchers. The following information was extracted from the included studies: the last name of the first author, year of publication, country, ethnicity, cancer type, source of cases and controls, number of cases and controls, genotyping method, genotype or allele frequency, and HWE p values for controls.

Statistical analysis

The study size was estimated using Power Analysis and Sample Size (PASS) 2021 (NCSS, LLC. Kaysville, Utah, USA) at a power value of 0.80. The chi-square test was used to assess differences in proportions between groups for the categorical variables. The median age of lung cancer patients, 57 years old, was used as cut-off value. The Hardy-Weinberg equilibrium was calculated using the chi-square test. Associations between CCND1 rs9344 and cancer susceptibility, therapeutic response and toxicity were estimated by unconditional logistic regression. Factors including age, sex, smoking status, stage, histological type, and chemotherapy regimens were considered as covaraites in this study. Survival curves were calculated using the Kaplan-Meier method, and survival analyses were conducted using Cox proportional hazards regression analysis. All significance tests were two-sided, and P <  0.05 was defined as statistically significant. The above analyses were performed using PLINK 1.9 and PASW statistics v18.0 (IBM Co., Armonk, NY, USA).

In the meta-analysis, the association between cancer risk and CCND1 rs9344 was assessed by calculating pooled OR and 95% CI. The heterogeneity of the effect size across studies was estimated and quantified by Cochrane’s Q test and I 2 test. The random effect model is selected if P <  0.1 or I 2  > 50%, otherwise, the fixed effect model is adopted. The stability of the results was assessed by sensitivity analysis. The inverted funnel plot was used to estimate the publication bias. All statistical analysis was performed in R4.2.3. P  < 0.05 was considered statistically significant.

Participants and descriptive data

In this study, 498 cases of lung cancer (394 males and 104 females) and 213 healthy controls (80 males and 133 females) were included. The clinical characteristics of the participants, including sex, age, histology, tumor stage, regimen, therapeutic response and toxicities were listed in Table  1 and Supplementary Table 1 . The genotype distribution of CCND1 rs9344 was in agreement with the Hardy Weinberg equilibrium ( P  = 0.539).

Association between CCND1 rs9344 and lung cancer susceptibility

After adjusting for age and sex, the association between CCND1 rs9344 polymorphism and cancer risk was analyzed in additive, dominant and recessive models, respectively. The results of logistic regression analysis were shown in Table  2 and Supplementary Tables 2 , and the OR values with 95%CI in different genetic models were as follows: additive model (GG vs. GA vs. AA: adjusted OR = 1.115, 95%CI = 0.869–1.431, P  = 0.391); dominant model (GA + AA vs. GG: adjusted OR = 0.980, 95%CI = 0.673–1.425, P  = 0.914); recessive model (AA vs. GG + GA: adjusted OR = 1.498, 95%CI = 0.935–2.399, P  = 0.0927). These results did not indicate a significant correlation between CCND1 rs9344 and the risk of lung cancer.

Subsequently, the stratified analyses were performed. As shown in Fig.  1 and Supplementary Table 3 , CCND1 rs9344 was significantly associated with adenocarcinoma (ADC) patients in the recessive model. The cancer susceptibility was higher in ADC patients with CCND1 rs9344 AA genotypes than in those with GG and GA genotypes (adjusted OR = 1.755, 95%CI = 1.057–2.912, P  = 0.030) (Fig.  1 ).

Stratification analyses of the association of CCND1 rs9344 with lung cancer risk. a – c  Additive ( a ), dominant ( b ), and recessive ( c ) models with adjustments of age and sex. Each box and horizontal line represent the odds ratio (OR) and 95% confidence interval (CI). NSCLC non-small cell lung carcinoma, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer

Association of CCND1 rs9344 and platinum-based chemotherapy response in lung cancer patients

Among the 498 cases of lung cancer, 467 of them had received more than two cycles of platinum-based chemotherapy. As shown in Table  1 and Supplementary Tables 1 , 283 responders and 184 non-responders were included, respectively. The unconditional logistic regression analysis was conducted after adjusting for the age, sex, stage, histological type, smoking status and chemotherapy regimen. However, no significant correlation was identified between CCND1 rs9344 polymorphism and platinum-based chemotherapy response (Table  2 and Supplementary Table 2 ) in the general overall pooled analysis.

However, CCND1 rs9344 was found to be significantly correlated with the platinum-based chemotherapy response of patients who received platinum + pemetrexed therapy (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P  = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P  = 0.022). In addition, a significant correlation was also found between CCND1 rs9344 and platinum-based chemotherapy response in the subgroup of ADC patients (recessive model: adjusted OR = 3.345, 95%CI = 1.276–8.765, P  = 0.014) (Fig.  2 and Supplementary Table 3 ).

Stratification analyses of the association of CCND1 rs9344 with platinum-based chemotherapy response. a – c  Additive ( a ), dominant ( b ), and recessive ( c ) models with adjustments of age, sex, stage, histological type, smoking status, and chemotherapy regimens. Each box and horizontal line represent the odds ratio (OR) and 95% confidence interval (CI). NSCLC non-small cell lung carcinoma, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer. Regimen1, platinum + gemcitabine. Regimen2, platinum + etoposide. Regimen3, platinum + pemetrexed

Association of CCND1 rs9344 with platinum‑based chemotherapy toxicity in lung cancer patients

Of the 467 lung cancer patients who received more than two cycles of platinum-based chemotherapy, 181 had undergone at least one type of severe toxicity. Grade 3–4 gastrointestinal and hematologic toxicities occurred in 101 and 114 patients, respectively (Table  1 and Supplementary Table 1 ). Unconditional logistic regression analysis demonstrated no significant correlation between CCND1 rs9344 and overall toxic reactions (Table  2 and Supplementary Table 2 ). However, CCND1 rs9344 was significantly correlated with overall toxicity in NSCLC patients in both the additive model (adjusted OR = 1.395, 95%CI = 1.025–1.897, P  = 0.034) and the recessive model (adjusted = 1.852, 95%CI = 1.088–3.152, P  = 0.023). The same tendency was also observed in ADC patients, with a significantly increased incidence of overall toxicity in both the additive model (adjusted OR = 1.547, 95%CI = 1.015–2.359, P  = 0.043) and the recessive model (adjusted OR = 2.030, 95%CI = 1.017–4.052, P  = 0.045) (Fig.  3 and Supplementary Table 3 ). The two types of toxicities were then analyzed separately. CCND1 rs9344 was significantly associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083–6.336, P  = 0.035) (Figs.  4 and 5 and Supplementary Table 3 ).

Stratification analyses of CCND1 rs9344 and chemotherapy-induced overall toxicity in lung cancer patients. a – c  Additive ( a ), dominant ( b ), and recessive ( c ) models with adjustments of age, sex, stage, histological type, smoking status, and chemotherapy regimens. Each box and horizontal line represent the odds ratio (OR) and 95% confidence interval (CI). NSCLC non-small cell lung carcinoma, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer. Regimen1, platinum + gemcitabine. Regimen2, platinum + etoposide. Regimen3, platinum + pemetrexed

Stratification analyses of CCND1 rs9344 and chemotherapy-induced gastrointestinal toxicity in lung cancer patients. a – c  Additive ( a ), dominant ( b ), and recessive ( c ) models with adjustments of age, sex, stage, histological type, smoking status, and chemotherapy regimens. Each box and horizontal line represent the odds ratio (OR) and 95% confidence interval (CI). NSCLC non-small cell lung carcinoma, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer. Regimen1, platinum + gemcitabine. Regimen2, platinum + etoposide. Regimen3, platinum + pemetrexed

Stratification analyses of CCND1 rs9344 and chemotherapy-induced hematological toxicity in lung cancer patients. a – c  Additive ( a ), dominant ( b ), and recessive ( c ) models with adjustments of age, sex, stage, histological type, smoking status, and chemotherapy regimens. Each box and horizontal line represent the odds ratio (OR) and 95% confidence interval (CI). NSCLC non-small cell lung carcinoma, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer. Regimen1, platinum + gemcitabine. Regimen2, platinum + etoposide. Regimen3, platinum + pemetrexed

Association of CCND1 rs9344 with 5-year overall survival in lung cancer patients

Finally, we analyzed the correlation between CCND1 rs9344 polymorphism and 5-year overall survival of lung cancer patients. Kaplan-Meier survival analyses were separately performed in three genetic models. Non-significant difference was observed in the 5-year overall survival rate between AA vs. GA vs. GG genotype patients ( P  = 0.226) (Fig.  6 a). We also did not find any significant correlation in the dominant and recessive models (dominant model: HR = 2.268 (0.9057-1.790), P  = 0.268; recessive model: HR = 1.065 (0.7983-1.420), P  = 0.483). Results of multivariate Cox propotional hazards regression were exhibited in Supplementary Table 4 .

Genotype of CCND1 rs9344 and its association with 5-year overall survival. a  AA vs. GA vs. GG; b  AA + GA vs. GG; c  AA vs. GA + GG

A meta-analysis elucidating the relationship between CCND1 rs9344 and lung cancer susceptibility

We then conducted a meta-analysis to assess the association between CCND1 rs9344 and lung cancer susceptibility. Following the process exhibited in Fig.  7 , a total of 104 relevant studies were retrieved according to the search formula, and 10 of them were finally included according to inclusion criteria. Table  3 summarized the characteristics of the selected studies evaluating the association of CCND1 rs9344 with lung cancer susceptibility. A total of 5432 cases and 6452 control samples were included. As seen in Table  4 , the overall OR with 95%CI did not indicate significant differences in the lung cancer risk in random effects (Fig.  8 ) and fixed effect models (Fig.  9 ). The funnel plots were used to check the publication bias, which indicated that there was no significant publication bias (Figs.  10 and 11 ). Both the Begg’s P -value and the Egger’s P -value were not significant (Table  4 ). Sensitivity analyses were performed to check the robustness of the meta-analysis results by neglecting one included study at a time. As shown in Fig.  12 , no single study was found to significantly influence the summary results.

Flow chart of the study selection process

Meta-analyses of correlation between CCND1 rs9344 and lung cancer risk under the random effects model. a  Codominant1 (GA VS GG); b  Codominant2 (AA VS GG); c  Codominant3 (AA VS GA); d  Dominant (AA + GA VS GG); e  Overdominant (GA VS AA + GG); f  Recessive (AA VS GA + GG); g  Allelic (A VS G). The boxes and horizontal lines indicate the risk ratio (RR) and 95% confidence interval (CI), respectively

Meta-analyses of correlation between CCND1 rs9344 and lung cancer risk under the fixed effects model. a  Codominant1 (GA VS GG); b  Codominant2 (AA VS GG); c  Codominant3 (AA VS GA); d  Dominant (AA + GA VS GG); e  Overdominant (GA VS AA + GG); f  Recessive (AA VS GA + GG); g  Allelic (A VS G). The boxes and horizontal lines indicate the risk ratio (RR) and 95% confidence interval (CI), respectively

Funnel plot of  CCND1 rs9344 and lung cancer risk under the random effects model. a  Codominant1 (GA VS GG); b  Codominant2 (AA VS GG); c  Codominant3 (AA VS GA); d  Dominant (AA + GA VS GG); e  Overdominant (GA VS AA + GG); f  Recessive (AA VS GA + GG); g  Allelic (A VS G)

Funnel plot of CCND1 rs9344 and lung cancer risk under the fixed effects model. a  Codominant1 (GA VS GG); b  Codominant2 (AA VS GG); ( c ) Codominant3 (AA VS GA); d  Dominant (AA + GA VS GG); e  Overdominant (GA VS AA + GG); f  Recessive (AA VS GA + GG); g  Allelic (A VS G)

Funnel plot of sensitivity analyses of meta-analysis. The sensitivity analyses were performed by omitting one included study at a time. The boxes and horizontal lines indicate the risk ratio (RR) and 95% confidence interval (CI), respectively

Lung cancer remains one of the leading disease burdens. While the last two decades have witnessed the emergence of novel therapeutic approaches such as targeted therapy and immunotherapy, platinum-based chemotherapy remains the most widely employed treatment for lung cancer patients. However, only a subset of patients could benefit from platinum-based chemotherapy, while the others, who prove insensitive to platinum drugs, endure the burdens of toxic side effects without any associated improvement in survival outcomes. Deeper insight into the pathogenesis, discovery of predictive biomarkers and optimization in therapeutic methods may efficiently improve the treatment outcome [ 48 , 49 , 50 ]. Based on this, one of the issues that urgently need to be addressed now discovering reliable biomarkers to identify individuals with a higher sensitivity to platinum-based chemotherapy. This expansion may provide promising possibilities for lung cancer diagnosis, treatment and prevention.

Unbalanced cycle regulation is one of the hallmarks of carcinogenesis. Cyclin D1 plays a crucial role in the transition from the G1 to the S phase of the cell cycle, thus being widely recognized as a pivotal element during the malignant transformation process [ 51 ]. The rs9344 (A870G), located in exon 4 of CCND1 gene, is a frequent gene polymorphism that regulates alternative splicing and enables the expression of the transcribed Cyclin D1b. The prediction value of CCND1 rs9344 in the prognosis of lung cancer patients has been investigated in several previous studies. However, few of them concentrated on platinum-based chemotherapy response. Hsia, et al. reported that among the lung cancer patients and cancer-free healthy controls, genotype distribution ( P  = 0.0003) and allelic frequency ( P  = 0.0007) of CCND1 rs9344 were significantly different. Individuals who carried the AG and GG genotypes had a 0.59- and 0.52-fold risk of lung cancer compared to the AA genotype, respectively (95% CI, 0.44–0.78 and 0.35–0.79) [ 40 ]. Sobti et al. also indicated that the AG genotype was correlated with a higher risk of lung cancer (OR = 1.7, 95% CI = 0.92–3.14) [ 46 ]. Gautschi, et al. found that CCND1 GG genotype was significantly correlated with platinum-based chemotherapy response ( P  = 0.04), while no significant difference was identified in patients’ prognosis among different genotypes [ 41 ]. However, Cakina, et al. indicated that no correlation was found in CCND1 A870G polymorphism between lung cancer patients and controls [ 43 ].

This study conducted a hospital-based case-control investigation focusing on lung cancer, and systematically investigated the association between CCND1 rs9344 and lung cancer susceptibility, platinum-based chemotherapy sensitivity, toxicity, and overall survival. While no significant differences were observed in the general population, the predictive potential of CCND1 rs9344 was established within specific patient subgroups. For cancer susceptibility, patients with the AA genotype exhibited a significantly higher risk than those with the GG + GA genotype (recessive model, adjusted OR = 1.755, 95%CI = 1.057–2.912, P  = 0.030). In the context of platinum-based chemotherapy, CCND1 rs9344 showed significant correlations with therapy response in patients receiving the PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P  = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P  = 0.022). This significant association was also observed among ADC patients (recessive model: adjusted OR = 3.345, 95%CI = 1.276–8.765, P  = 0.014). Furthermore, an increased risk of overall toxicity was found in both NSCLC (additive model: adjusted OR = 1.395, 95%CI = 1.025–1.897, P  = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088–3.152, P  = 0.023) and ADC patients (additive model: adjusted OR = 1.547, 95%CI = 1.015–2.359, P  = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017–4.052, P  = 0.045). Notably, in non-smokers, CCND1 rs9344 was significantly associated with a higher risk of gastrointestinal toxicity (adjusted OR = 2.620, 95%CI = 1.083–6.336, P  = 0.035).

In addition to the case-control study, a comprehensive meta-analysis for previous research on CCND1 rs9344 and lung cancer susceptibility was conducted. In line with our findings, no significant correlation was observed on a overall scale. This may arise from various factors such as variations in sample selection and distribution, disparities in research quality, substantial heterogeneity in environmental factors, or gene-environment interactions. The results of our study and meta-analysis consistently suggest that the predictive role of CCND1 rs9344 in therapeutic efficacy and prognosis of lung cancer patients may not be effective for all individuals, but rather requires more precise subgroup analysis. Besides, the lack of statistical significance at the overall level may also be caused by various factors in different studies, including differences in sample selection and distribution, variations in study quality, substantial heterogeneity of environmental factors, or gene-environment interactions. The predictive value of CCND1 rs9344 remains to be further validated in large samples through stratified analysis.

To summarize, this study demonstrated that CCND1 rs9344 may be considered a candidate biomarker for cancer susceptibility and therapeutic outcome in certain patient subgroups in Chinese population. Further stratified studies with larger sample sizes are needed to confirm the results.

Availability of data and materials

The data presented in this study are available on request from the corresponding author.

Abbreviations

Adenocarcinoma

Complete response

Progressive disease

Partial response

Stable disease

Single nucleotide polymorphisms

Oliver AL. Lung Cancer: Epidemiology and Screening. Surg Clin North Am. 2022;102:335–44.

Article   PubMed   Google Scholar  

Jenkins R, Walker J. and U. B. Roy 2022 cancer statistics: focus on lung cancer. Future Oncol 2023.

Jakobsen E, Olsen KE, Bliddal M, Hornbak M. Persson and A. Green forecasting lung cancer incidence, mortality, and prevalence to year 2030. BMC Cancer. 2021;21:985.

Article   PubMed   PubMed Central   Google Scholar  

Thai AA, Solomon BJ, Sequist LV, Gainor JF. Heist lung cancer. Lancet. 2021;398:535–54.

Siegel RL, Miller KD. Fuchs and A. Jemal Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33.

Deshpand R, Chandra M. Rauthan Evolving trends in lung cancer: epidemiology, diagnosis, and management. Indian J Cancer. 2022;59:S90–105.

Harethardottir H, Jonsson S, Gunnarsson O, Hilmarsdottir B, Asmundsson J, Gudmundsdottir I, Saevarsdottir VY, Hansdottir S, Hannesson P. Gudbjartsson [Advances in lung cancer diagnosis and treatment - a review]. Laeknabladid. 2022;108:17–29.

Google Scholar  

Nooreldeen R. and H. Bach Current and Future Development in Lung Cancer diagnosis. Int J Mol Sci 2021; 22.

Hsiao SH, Chen WT, Chung CL, Chou YT, Lin SE, Hong SY, Chang JH. Chang and L. N. Chien comparative survival analysis of platinum-based adjuvant chemotherapy for early-stage squamous cell carcinoma and adenocarcinoma of the lung. Cancer Med. 2022;11:2067–78.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Szejniuk WM, Cekala M, Bogsted M, Meristoudis C, McCulloch; T, Falkmer UG. Roe Adjuvant platinum-based chemotherapy in non-small cell lung cancer: the role of relative dose-intensity and treatment delay. Cancer Treat Res Commun. 2021;27:100318.

Article   CAS   PubMed   Google Scholar  

Griesinger F, Korol EE, Kayaniyil S, Varol N, Ebner T. Goring Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: a meta-analysis. Lung Cancer. 2019;135:196–204.

Zugazagoitia J. Paz-ares extensive-stage small-cell Lung Cancer: first-line and second-line treatment options. J Clin Oncol. 2022;40:671–80.

Liu W, Wang Y, Luo J, Yuan H. Luo Genetic Polymorphisms and platinum-based Chemotherapy-Induced toxicities in patients with Lung Cancer: a systematic review and Meta-analysis. Front Oncol. 2019;9:1573.

Gong WJ, Ma LY, Hu L, Lv YN, Huang H, Xu JQ, Huang DD, Liu RJ, Han Y, Zhang Y, et al. STAT3 rs4796793 contributes to lung cancer risk and clinical outcomes of platinum-based chemotherapy. Int J Clin Oncol. 2019;24:476–84.

Szejniuk WM, Robles AI, McCulloch T, Falkmer UGI. Roe Epigenetic predictive biomarkers for response or outcome to platinum-based chemotherapy in non-small cell lung cancer, current state-of-art. Pharmacogenomics J. 2019;19:5–14.

Li C, Wang H, Jiang Y, Fu W, Liu X, Zhong R, Cheng B, Zhu F, Xiang Y, He J, et al. Advances in lung cancer screening and early detection. Cancer Biol Med. 2022;19:591–608.

Montalto FI. and F. De Amicis Cyclin D1 in Cancer: a molecular connection for cell cycle control, Adhesion and Invasion in Tumor and Stroma. Cells 2020; 9.

Knudsen ES, Kumarasamy V, Nambiar R, Pearson JD, Vail P, Rosenheck H, Wang J, Eng K, Bremner R, Schramek D, et al. CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities. Cell Rep. 2022;38:110448.

O’Connor MJ, Thakar T, Nicolae CM. Moldovan PARP14 regulates cyclin D1 expression to promote cell-cycle progression. Oncogene. 2021;40:4872–83.

Tchakarska G. Sola the double dealing of cyclin D1. Cell Cycle. 2020;19:163–78.

Zhu D, Huang J, Liu N, Li W. Yan PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration. Cell Death Dis. 2021;12:730.

Lin RJ, Lubpairee T, Liu KY, Anderson DW, Durham S. Poh Cyclin D1 overexpression is associated with poor prognosis in oropharyngeal cancer. J Otolaryngol Head Neck Surg. 2013;42:23.

Zhang B, Liu W, Li L, Lu J, Liu M, Sun Y. Jin KAI1/CD82 and cyclin D1 as biomarkers of invasion, metastasis and prognosis of laryngeal squamous cell carcinoma. Int J Clin Exp Pathol. 2013;6:1060–7.

CAS   PubMed   PubMed Central   Google Scholar  

Ai T, Wang Z, Zhang M, Zhang L, Wang N, Li W. Song expression and prognostic relevance of STAT3 and cyclin D1 in non-small cell lung cancer. Int J Biol Markers. 2012;27:e132–138.

Valla M, Klaestad E, Ytterhus B. Bofin CCND1 amplification in breast Cancer -associations with proliferation, histopathological Grade, Molecular Subtype and Prognosis. J Mammary Gland Biol Neoplasia. 2022;27:67–77.

Ramos-Garcia P, Gil-Montoya JA, Scully C, Ayen A, Gonzalez-Ruiz L, Navarro-Trivino FJ. Gonzalez-Moles an update on the implications of cyclin D1 in oral carcinogenesis. Oral Dis. 2017;23:897–912.

Kuwahara M, Hirai T, Yoshida K, Yamashita Y, Hihara J. Inoue and T. Toge p53, p21(Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer. Dis Esophagus. 1999;12:116–9.

Yaylim-Eraltan I, Arikan S, Yildiz Y, Cacina C, Ergen HA, Tuna G, Gormus U. Zeybek and T. Isbir the influence of cyclin D1 A870G polymorphism on colorectal cancer risk and prognosis in a Turkish population. Anticancer Res. 2010;30:2875–80.

CAS   PubMed   Google Scholar  

Holah NS. Hemida Cyclin D1 and PSA act as good prognostic and clinicopathological indicators for breast cancer. J Immunoass Immunochem. 2020;41:28–44.

Article   CAS   Google Scholar  

Liu J, Lin J, Wang X, Zheng X, Gao X, Huang Y, Chen G, Xiong J, Lan B, Chen C, et al. CCND1 amplification profiling identifies a subtype of Melanoma Associated with Poor Survival and an immunosuppressive Tumor Microenvironment. Front Immunol. 2022;13:725679.

Fang L, Xu X, Zheng W, Wu L. Wan the expression of microRNA-340 and cyclin D1 and its relationship with the clinicopathological characteristics and prognosis of lung cancer. Asian J Surg. 2021;44:1363–9.

Li S, Xu J. You the pathologic diagnosis of mantle cell lymphoma. Histol Histopathol. 2021;36:1037–51.

Srinivasan S, Clements JA. Batra single nucleotide polymorphisms in clinics: Fantasy or reality for cancer? Crit Rev Clin Lab Sci. 2016;53:29–39.

Stenzel-Bembenek A, Sagan D, Guz M. Stepulak [Single nucleotide polymorphisms in lung cancer patients and cisplatin treatment]. Postepy Hig Med Dosw (Online). 2014;68:1361–73.

Tebbutt SJ, James A. Pare single-nucleotide polymorphisms and lung disease: clinical implications. Chest. 2007;131:1216–23.

Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899–905.

Qie S. Diehl Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med (Berl). 2016;94:1313–26.

Pandey A, Bahl C, Sharma S, Singh N. Behera Functional role of CyclinD1 polymorphism (G870A) in modifying susceptibility and overall survival of north Indian lung cancer patients. Tumori. 2018;104:179–87.

Hung RJ, Boffetta P, Canzian F, Moullan N, Szeszenia-Dabrowska N, Zaridze D, Lissowska J, Rudnai P, Fabianova E, Mates D, et al. Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe. Cancer Res. 2006;66:8280–6.

Hsia TC, Liu CJ, Lin CH, Chang WS, Chu CC, Hang LW, Lee HZ. Lo and D. T. Bau Interaction of CCND1 genotype and smoking habit in Taiwan lung cancer patients. Anticancer Res. 2011;31:3601–5.

Gautschi O, Hugli B, Ziegler A, Bigosch C, Bowers NL, Ratschiller D, Jermann M, Stahel RA, Heighway J. Betticher Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2006;51:303–11.

Catarino R, Coelho A, Nogueira A, Araujo A, Gomes M, Lopes C. Medeiros Cyclin D1 polymorphism in non-small cell lung cancer in a Portuguese population. Cancer Biomark. 2012;12:65–72.

Cakina S, Gulyasar T, Ozen A, Sipahi T, Kocak Z. Sener relationship between cyclin D1 (A870G) gene polymorphism and lung cancer. Indian J Biochem Biophys. 2013;50:233–6.

Perez-Morales R, Mendez-Ramirez I, Moreno-Macias H, Mendoza-Posadas AD, Martinez-Ramirez OC, Castro-Hernandez C. Gonsebatt and J. Rubio Genetic susceptibility to lung cancer based on candidate genes in a sample from the Mexican mestizo population: a case-control study. Lung. 2014;192:167–73.

Qiuling S, Yuxin Z, Suhua Z, Cheng X. Shuguang and H. Fengsheng Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population. Carcinogenesis. 2003;24:1499–503.

Sobti RC, Kaur P, Kaur S, Singh J, Janmeja AK, Jindal SK, Kishan J. Raimondi effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a north Indian population. Cancer Genet Cytogenet. 2006;170:108–14.

Wang W, Spitz MR, Yang H, Lu C. Stewart and X. Wu Genetic variants in cell cycle control pathway confer susceptibility to lung cancer. Clin Cancer Res. 2007;13:5974–81.

Purkayastha K, Dhar R, Pethusamy K, Srivastava T, Shankar A. Rath and S. Karmakar the issues and challenges with cancer biomarkers. J Cancer Res Ther. 2023;19:S20–35.

Norris RP, Dew R, Sharp L, Greystoke A, Rice S. Johnell and A. Todd Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis. BMC Med. 2020;18:282.

Sha D, Jin Z, Budczies J, Kluck K, Stenzinger A. Sinicrope Tumor Mutational Burden as a predictive biomarker in solid tumors. Cancer Discov. 2020;10:1808–25.

Gautschi O, Ratschiller D, Gugger M, Betticher DC. Heighway Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer. 2007;55:1–14.

Download references

Acknowledgements

The authors acknowledge the participants for their contribution to the study.

This work was supported by grants from The National Natural Science Foundation of China (No. 82304634, 82003868). Hubei Provincial Natural Science Foundation of China (No. 2023AFD022, 2020CFB388). Key Research and Development Program of Hubei Province (No.2020BCA060). Scientific Research Projects of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (No. 2022xhyn055).

Author information

Authors and affiliations.

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Chao Mei, Baoli Xu, Sanlan Wu, Yongning Lv, Yu Zhang & Weijing Gong

Department of General medicine, Huangshi Central Hospital, The Affifiliated Hospital of Hubei Polytechnic University, Huangshi, China

People’s Hospital Of Chong Qing Liang Jiang New Area, Chongqing, China

Xuelin Zhang

Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

Zhaoqian Liu

Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, China

Weijing Gong

You can also search for this author in PubMed   Google Scholar

Contributions

WG, ZL, YZ and YL contributed to the design of the study. TW, BX, XZ and SW provided help for data collection, CM and WG performed data analysis and manuscript write up. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Weijing Gong .

Ethics declarations

Ethics approval and consent to participate.

This study was approved by the Ethics Committee of Xiangya School of Medicine, Central South University (registration number: CTXY-110008-2). 01/09/2011-01/09/2015. Informed consent was obtained from all subjects involved in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Supplementary material 1., rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Mei, C., Wang, T., Xu, B. et al. Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study. BMC Pulm Med 24 , 167 (2024). https://doi.org/10.1186/s12890-024-02983-1

Download citation

Received : 04 August 2023

Accepted : 26 March 2024

Published : 08 April 2024

DOI : https://doi.org/10.1186/s12890-024-02983-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Lung cancer
• CCND1 rs9344
• Platinum-based chemotherapy
• Susceptibility

BMC Pulmonary Medicine

ISSN: 1471-2466

• Submission enquiries: [email protected]
• General enquiries: [email protected]

An official website of the United States government

The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• Browse Titles

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Case study: 33-year-old female presents with chronic sob and cough.

Sandeep Sharma ; Muhammad F. Hashmi ; Deepa Rawat .

Affiliations

Last Update: February 20, 2023 .

• Case Presentation

History of Present Illness:  A 33-year-old white female presents after admission to the general medical/surgical hospital ward with a chief complaint of shortness of breath on exertion. She reports that she was seen for similar symptoms previously at her primary care physician’s office six months ago. At that time, she was diagnosed with acute bronchitis and treated with bronchodilators, empiric antibiotics, and a short course oral steroid taper. This management did not improve her symptoms, and she has gradually worsened over six months. She reports a 20-pound (9 kg) intentional weight loss over the past year. She denies camping, spelunking, or hunting activities. She denies any sick contacts. A brief review of systems is negative for fever, night sweats, palpitations, chest pain, nausea, vomiting, diarrhea, constipation, abdominal pain, neural sensation changes, muscular changes, and increased bruising or bleeding. She admits a cough, shortness of breath, and shortness of breath on exertion.

Social History: Her tobacco use is 33 pack-years; however, she quit smoking shortly prior to the onset of symptoms, six months ago. She denies alcohol and illicit drug use. She is in a married, monogamous relationship and has three children aged 15 months to 5 years. She is employed in a cookie bakery. She has two pet doves. She traveled to Mexico for a one-week vacation one year ago.

Allergies:  No known medicine, food, or environmental allergies.

Past Medical History: Hypertension

Past Surgical History: Cholecystectomy

Medications: Lisinopril 10 mg by mouth every day

Physical Exam:

Vitals: Temperature, 97.8 F; heart rate 88; respiratory rate, 22; blood pressure 130/86; body mass index, 28

General: She is well appearing but anxious, a pleasant female lying on a hospital stretcher. She is conversing freely, with respiratory distress causing her to stop mid-sentence.

Respiratory: She has diffuse rales and mild wheezing; tachypneic.

Cardiovascular: She has a regular rate and rhythm with no murmurs, rubs, or gallops.

Gastrointestinal: Bowel sounds X4. No bruits or pulsatile mass.

• Initial Evaluation

Laboratory Studies:  Initial work-up from the emergency department revealed pancytopenia with a platelet count of 74,000 per mm3; hemoglobin, 8.3 g per and mild transaminase elevation, AST 90 and ALT 112. Blood cultures were drawn and currently negative for bacterial growth or Gram staining.

Chest X-ray

Impression:  Mild interstitial pneumonitis

• Differential Diagnosis
• Aspiration pneumonitis and pneumonia
• Bacterial pneumonia
• Immunodeficiency state and Pneumocystis jiroveci pneumonia
• Carcinoid lung tumors
• Tuberculosis
• Viral pneumonia
• Chlamydial pneumonia
• Coccidioidomycosis and valley fever
• Recurrent Legionella pneumonia
• Mediastinal cysts
• Mediastinal lymphoma
• Recurrent mycoplasma infection
• Pancoast syndrome
• Pneumococcal infection
• Sarcoidosis
• Small cell lung cancer
• Aspergillosis
• Blastomycosis
• Histoplasmosis
• Actinomycosis
• Confirmatory Evaluation

CT of the chest was performed to further the pulmonary diagnosis; it showed a diffuse centrilobular micronodular pattern without focal consolidation.

On finding pulmonary consolidation on the CT of the chest, a pulmonary consultation was obtained. Further history was taken, which revealed that she has two pet doves. As this was her third day of broad-spectrum antibiotics for a bacterial infection and she was not getting better, it was decided to perform diagnostic bronchoscopy of the lungs with bronchoalveolar lavage to look for any atypical or rare infections and to rule out malignancy (Image 1).

Bronchoalveolar lavage returned with a fluid that was cloudy and muddy in appearance. There was no bleeding. Cytology showed Histoplasma capsulatum .

Based on the bronchoscopic findings, a diagnosis of acute pulmonary histoplasmosis in an immunocompetent patient was made.

Pulmonary histoplasmosis in asymptomatic patients is self-resolving and requires no treatment. However, once symptoms develop, such as in our above patient, a decision to treat needs to be made. In mild, tolerable cases, no treatment other than close monitoring is necessary. However, once symptoms progress to moderate or severe, or if they are prolonged for greater than four weeks, treatment with itraconazole is indicated. The anticipated duration is 6 to 12 weeks total. The response should be monitored with a chest x-ray. Furthermore, observation for recurrence is necessary for several years following the diagnosis. If the illness is determined to be severe or does not respond to itraconazole, amphotericin B should be initiated for a minimum of 2 weeks, but up to 1 year. Cotreatment with methylprednisolone is indicated to improve pulmonary compliance and reduce inflammation, thus improving work of respiration. [1] [2] [3]

Histoplasmosis, also known as Darling disease, Ohio valley disease, reticuloendotheliosis, caver's disease, and spelunker's lung, is a disease caused by the dimorphic fungi  Histoplasma capsulatum native to the Ohio, Missouri, and Mississippi River valleys of the United States. The two phases of Histoplasma are the mycelial phase and the yeast phase.

Etiology/Pathophysiology 

Histoplasmosis is caused by inhaling the microconidia of  Histoplasma  spp. fungus into the lungs. The mycelial phase is present at ambient temperature in the environment, and upon exposure to 37 C, such as in a host’s lungs, it changes into budding yeast cells. This transition is an important determinant in the establishment of infection. Inhalation from soil is a major route of transmission leading to infection. Human-to-human transmission has not been reported. Infected individuals may harbor many yeast-forming colonies chronically, which remain viable for years after initial inoculation. The finding that individuals who have moved or traveled from endemic to non-endemic areas may exhibit a reactivated infection after many months to years supports this long-term viability. However, the precise mechanism of reactivation in chronic carriers remains unknown.

Infection ranges from an asymptomatic illness to a life-threatening disease, depending on the host’s immunological status, fungal inoculum size, and other factors. Histoplasma  spp. have grown particularly well in organic matter enriched with bird or bat excrement, leading to the association that spelunking in bat-feces-rich caves increases the risk of infection. Likewise, ownership of pet birds increases the rate of inoculation. In our case, the patient did travel outside of Nebraska within the last year and owned two birds; these are her primary increased risk factors. [4]

Non-immunocompromised patients present with a self-limited respiratory infection. However, the infection in immunocompromised hosts disseminated histoplasmosis progresses very aggressively. Within a few days, histoplasmosis can reach a fatality rate of 100% if not treated aggressively and appropriately. Pulmonary histoplasmosis may progress to a systemic infection. Like its pulmonary counterpart, the disseminated infection is related to exposure to soil containing infectious yeast. The disseminated disease progresses more slowly in immunocompetent hosts compared to immunocompromised hosts. However, if the infection is not treated, fatality rates are similar. The pathophysiology for disseminated disease is that once inhaled, Histoplasma yeast are ingested by macrophages. The macrophages travel into the lymphatic system where the disease, if not contained, spreads to different organs in a linear fashion following the lymphatic system and ultimately into the systemic circulation. Once this occurs, a full spectrum of disease is possible. Inside the macrophage, this fungus is contained in a phagosome. It requires thiamine for continued development and growth and will consume systemic thiamine. In immunocompetent hosts, strong cellular immunity, including macrophages, epithelial, and lymphocytes, surround the yeast buds to keep infection localized. Eventually, it will become calcified as granulomatous tissue. In immunocompromised hosts, the organisms disseminate to the reticuloendothelial system, leading to progressive disseminated histoplasmosis. [5] [6]

Symptoms of infection typically begin to show within three to17 days. Immunocompetent individuals often have clinically silent manifestations with no apparent ill effects. The acute phase of infection presents as nonspecific respiratory symptoms, including cough and flu. A chest x-ray is read as normal in 40% to 70% of cases. Chronic infection can resemble tuberculosis with granulomatous changes or cavitation. The disseminated illness can lead to hepatosplenomegaly, adrenal enlargement, and lymphadenopathy. The infected sites usually calcify as they heal. Histoplasmosis is one of the most common causes of mediastinitis. Presentation of the disease may vary as any other organ in the body may be affected by the disseminated infection. [7]

The clinical presentation of the disease has a wide-spectrum presentation which makes diagnosis difficult. The mild pulmonary illness may appear as a flu-like illness. The severe form includes chronic pulmonary manifestation, which may occur in the presence of underlying lung disease. The disseminated form is characterized by the spread of the organism to extrapulmonary sites with proportional findings on imaging or laboratory studies. The Gold standard for establishing the diagnosis of histoplasmosis is through culturing the organism. However, diagnosis can be established by histological analysis of samples containing the organism taken from infected organs. It can be diagnosed by antigen detection in blood or urine, PCR, or enzyme-linked immunosorbent assay. The diagnosis also can be made by testing for antibodies again the fungus. [8]

Pulmonary histoplasmosis in asymptomatic patients is self-resolving and requires no treatment. However, once symptoms develop, such as in our above patient, a decision to treat needs to be made. In mild, tolerable cases, no treatment other than close monitoring is necessary. However, once symptoms progress to moderate or severe or if they are prolonged for greater than four weeks, treatment with itraconazole is indicated. The anticipated duration is 6 to 12 weeks. The patient's response should be monitored with a chest x-ray. Furthermore, observation for recurrence is necessary for several years following the diagnosis. If the illness is determined to be severe or does not respond to itraconazole, amphotericin B should be initiated for a minimum of 2 weeks, but up to 1 year. Cotreatment with methylprednisolone is indicated to improve pulmonary compliance and reduce inflammation, thus improving the work of respiration.

The disseminated disease requires similar systemic antifungal therapy to pulmonary infection. Additionally, procedural intervention may be necessary, depending on the site of dissemination, to include thoracentesis, pericardiocentesis, or abdominocentesis. Ocular involvement requires steroid treatment additions and necessitates ophthalmology consultation. In pericarditis patients, antifungals are contraindicated because the subsequent inflammatory reaction from therapy would worsen pericarditis.

Patients may necessitate intensive care unit placement dependent on their respiratory status, as they may pose a risk for rapid decompensation. Should this occur, respiratory support is necessary, including non-invasive BiPAP or invasive mechanical intubation. Surgical interventions are rarely warranted; however, bronchoscopy is useful as both a diagnostic measure to collect sputum samples from the lung and therapeutic to clear excess secretions from the alveoli. Patients are at risk for developing a coexistent bacterial infection, and appropriate antibiotics should be considered after 2 to 4 months of known infection if symptoms are still present. [9]

Prognosis 

If not treated appropriately and in a timely fashion, the disease can be fatal, and complications will arise, such as recurrent pneumonia leading to respiratory failure, superior vena cava syndrome, fibrosing mediastinitis, pulmonary vessel obstruction leading to pulmonary hypertension and right-sided heart failure, and progressive fibrosis of lymph nodes. Acute pulmonary histoplasmosis usually has a good outcome on symptomatic therapy alone, with 90% of patients being asymptomatic. Disseminated histoplasmosis, if untreated, results in death within 2 to 24 months. Overall, there is a relapse rate of 50% in acute disseminated histoplasmosis. In chronic treatment, however, this relapse rate decreases to 10% to 20%. Death is imminent without treatment.

• Pearls of Wisdom

While illnesses such as pneumonia are more prevalent, it is important to keep in mind that more rare diseases are always possible. Keeping in mind that every infiltrates on a chest X-ray or chest CT is not guaranteed to be simple pneumonia. Key information to remember is that if the patient is not improving under optimal therapy for a condition, the working diagnosis is either wrong or the treatment modality chosen by the physician is wrong and should be adjusted. When this occurs, it is essential to collect a more detailed history and refer the patient for appropriate consultation with a pulmonologist or infectious disease specialist. Doing so, in this case, yielded workup with bronchoalveolar lavage and microscopic evaluation. Microscopy is invaluable for definitively diagnosing a pulmonary consolidation as exemplified here where the results showed small, budding, intracellular yeast in tissue sized 2 to 5 microns that were readily apparent on hematoxylin and eosin staining and minimal, normal flora bacterial growth. 

• Enhancing Healthcare Team Outcomes

This case demonstrates how all interprofessional healthcare team members need to be involved in arriving at a correct diagnosis. Clinicians, specialists, nurses, pharmacists, laboratory technicians all bear responsibility for carrying out the duties pertaining to their particular discipline and sharing any findings with all team members. An incorrect diagnosis will almost inevitably lead to incorrect treatment, so coordinated activity, open communication, and empowerment to voice concerns are all part of the dynamic that needs to drive such cases so patients will attain the best possible outcomes.

• Review Questions
• Access free multiple choice questions on this topic.
• Comment on this article.

Histoplasma Contributed by Sandeep Sharma, MD

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Hashmi declares no relevant financial relationships with ineligible companies.

Disclosure: Deepa Rawat declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Sharma S, Hashmi MF, Rawat D. Case Study: 33-Year-Old Female Presents with Chronic SOB and Cough. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

In this Page

Bulk download.

• Bulk download StatPearls data from FTP

Related information

• PMC PubMed Central citations
• PubMed Links to PubMed

Similar articles in PubMed

• Review Palliative Chemotherapy: Does It Only Provide False Hope? The Role of Palliative Care in a Young Patient With Newly Diagnosed Metastatic Adenocarcinoma. [J Adv Pract Oncol. 2017] Review Palliative Chemotherapy: Does It Only Provide False Hope? The Role of Palliative Care in a Young Patient With Newly Diagnosed Metastatic Adenocarcinoma. Doverspike L, Kurtz S, Selvaggi K. J Adv Pract Oncol. 2017 May-Jun; 8(4):382-386. Epub 2017 May 1.
• Review Breathlessness with pulmonary metastases: a multimodal approach. [J Adv Pract Oncol. 2013] Review Breathlessness with pulmonary metastases: a multimodal approach. Brant JM. J Adv Pract Oncol. 2013 Nov; 4(6):415-22.
• A 50-Year Old Woman With Recurrent Right-Sided Chest Pain. [Chest. 2022] A 50-Year Old Woman With Recurrent Right-Sided Chest Pain. Saha BK, Bonnier A, Chong WH, Chenna P. Chest. 2022 Feb; 161(2):e85-e89.
• Suicidal Ideation. [StatPearls. 2024] Suicidal Ideation. Harmer B, Lee S, Duong TVH, Saadabadi A. StatPearls. 2024 Jan
• Review Domperidone. [Drugs and Lactation Database (...] Review Domperidone. . Drugs and Lactation Database (LactMed®). 2006

Recent Activity

• Case Study: 33-Year-Old Female Presents with Chronic SOB and Cough - StatPearls Case Study: 33-Year-Old Female Presents with Chronic SOB and Cough - StatPearls

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Connect with NLM

National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894

Web Policies FOIA HHS Vulnerability Disclosure

Help Accessibility Careers