Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

Abstract

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

“…On the other hand, there was an absence of correlation for lung cancer between studies in nonsmoking Asian females and a Caucasian population where case patients were primarily smokers. This result is consistent with the observation that distinct sets of susceptibility SNPs have emerged in these two populations (29,30). In general, low correlation across populations can be caused by different causal SNPs, differences in effect sizes or allele frequencies of shared causal SNPs, and differences in linkage disequilibrium (LD).…”

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

“…Hodgkin lymphoma [26], and most recently a risk marker factor in Asian females for lung cancer [27]. Our results replicated the strong male specificity of the risk for childhood ALL, specifically in non-Hispanic White males, with no association in Hispanics.…”

“…The SNP near the HLA-DRA gene, rs2395185, is a marker for the HLA-DRB4 (DR53) lineage [23]. The HLA-DRB4 lineage or its marker SNP have been previously shown as a risk marker in lung cancer [27], asthma [29], rheumatoid arthritis [28], type I diabetes [44], adult acute myeloblastic leukemia [45], chronic myeloid leukemia [46], chronic lymphoid leukemia [47][48][49] and in childhood ALL (males only) [24,50,51], and as a protective marker for non-Hodgkin lymphoma [26], and ulcerative colitis [30][31][32]52]. The DRB4/DR53 lineage has been shown previously to have a risk association with childhood ALL, with male specificity, within a European sample via HLA typing [24].…”

“…We re-examined five previously discovered single nucleotide polymorphisms (SNPs) of known associations to leukemia (rs7089424, rs10821936, rs10994982, rs4132601, and rs2239633), along with three HLA region susceptibility markers for lymphomas, since lymphoma and ALL both stem from lymphoid cells. These included rs2395185, a marker of HLA DRB4 lineage [23] which has previously shown associations with major leukemias including childhood ALL [24,25] and other diseases including Hodgkin lymphoma [26], lung cancer [27], rheumatoid arthritis [28], asthma [29], and ulcerative colitis [30][31][32]; rs10484561, which has been shown to be a strong risk marker in follicular lymphoma (FL) [33]; and rs2647012, which is a protective marker for FL [34]. These SNPs were examined in a multiethnic sample (non-Hispanic Whites, Hispanic Whites, and Blacks) from Houston, Texas to assess their association with ALL.…”

The Genetic Polymorphisms of TERT-CLPTM1L and Lung Cancer Susceptibility: A Meta-Analysis

“…McKay et al did not report heterogeneity with respect to histology, gender or smoking status [12]. However recent reports indicate that the association between rs2736100 and lung cancer risk is more evident for adenocarcinoma, females, nondrinkers, nonsmokers and cooking oil fume exposure [10,[13][14][15][16]. Myneni et al reported that TERT was more prominently associated with lung cancer in participants who were older than 60 years, exposed to low indoor air pollution and adenocarcinoma and squamous cell carcinoma [17].…”