Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers.
Genome-wide association studies have provided evidence that common variation at 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) influences lung cancer risk. To examine if variation at any of these loci influences the risk of lung cancer in never-smokers, we compared 5p15.33-TERT (rs2736100), 5p15.33-CLPTM1L (rs4975616), 6p21.33-BAT3 (rs3117582), 15q25.1-CHRNA3 (rs8042374) and 15q25.1-CHRNA3 (rs12914385) genotypes in a series of 239 never-smoker lung cancer cases and 553 never-smoker controls. A statistically significant association between lung cancer risk and 5p15.33 genotypes was found: rs2736100 (odds ratio = 0.78, 95% confidence interval: 0.63-0.97; P = 0.02), rs4975616 (odds ratio = 0.69, 95% confidence interval: 0.55-0.85; P = 7.95 x 10(-4)), primarily for adenocarcinoma. There was no evidence of association between 6p21.33 or 15q25.1 variation and risk of lung cancer. This analysis provides evidence that TERT-CLPTM1L variants may influence the risk of lung cancer outside the context of tobacco smoking.
Wang
Yufei
Y
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Broderick
Peter
P
Matakidou
Athena
A
Eisen
Timothy
T
Houlston
Richard S
RS
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000556:secondary; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011978:Receptors, Nicotinic / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D019098:Telomerase; C092009:BAG6 protein, human; C447158:CHRNA5 protein, human; C422445:CLPTM1L protein, human; C509186:TERT protein, human