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The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

ABSTRACT: BACKGROUND/AIMS:Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers. METHODS:This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay. RESULTS:Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma. CONCLUSION:These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.

SUBMITTER: Yoo SS

PROVIDER: S-EPMC7373985 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

Yoo Seung Soo SS Kang Hyo-Gyoung HG Choi Jin Eun JE Hong Mi Jeong MJ Do Sook Kyung SK Lee Jang Hyuck JH Lee Won Kee WK Lee Shin Yup SY Lee Jaehee J Cha Seung Ick SI Kim Chang Ho CH Lee Eung Bae EB Park Jae Yong JY

The Korean journal of internal medicine 20191230 4

<h4>Background/aims</h4>Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers.<h4>Methods</h4>This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay.<h4>Resul ...[more]

PMID: 31878769

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Project description:ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and methodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

Dataset Information

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

Publications

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

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