The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Abstract

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Decreased risk of developing lung cancer in subjects carrying the CLPTM1L rs401681 (G>A) polymorphism: evidence from a meta-analysis

“…In addition, 5p15.33 was recently identified as a susceptibility region for lung cancer, where the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes are located (Kang et al, 2008;McKay et al, 2008;Wang et al, 2008;Jin et al, 2009;Rafnar et al, 2009;Zienolddiny et al, 2009;Hsiung et al, 2010). TERT is a main functional subunit and key regulator of the telomerase enzyme.…”

Multiple variants of TERT and CLPTM1L constitute risk factors for lung adenocarcinoma

“…Several lung cancer susceptibility loci have recently been identified in genome-wide association studies (Easton and Eeles, 2008; Thomas et al, 2008;Boezen, 2009;Caporaso et al, 2009;Landi et al, 2009;Chung et al, 2010;Hsiung et al, 2010). 5p15.33 was recently identified as a susceptibility region for lung cancer, and two known genes (telomerase reverse transcriptase [TERT] and palate transmembrane 1-like [CLPTM1L]) are located in this region.…”

Association of genetic polymorphisms in TERT-CLPTM1L with lung cancer in a Chinese population

“…This result is in line with those of previous reports. The association of rs2736100 with lung cancer susceptibility has also been reported in geographically separated cohorts and in populations that have smoked and never smoked (McKay et al, 2008;Hsiung et al, 2010). Therefore, we hypothesize that rs2736100 is an important locus in the relationship between TERT-CLPTM1L and lung cancer risk.…”