Genome-wide analysis has identified three new susceptibility loci for lung cancer in a large cohort of never-smoking women in Asia.
The study, reported in a letter to Nature Genetics, also confirmed associations at three other loci and excluded a fourth locus as being involved in lung cancer risk independently of smoking.
"It is notable that our strongest finding at 10q25.2 has not been reported previously in lung cancer genome-wide association studies," write Qing Lan (National Cancer Institute, Bethesda, Maryland, USA) and co-authors. "This observation suggests that the etiology of lung cancer in never smokers in Asia may have unique genetic characteristics."
Lan et al performed a genome-wide association study involving 5510 never-smoking women with lung cancer and 4544 cancer-free control women; participants were drawn from 14 studies based in mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong.
The initial analysis revealed two associations at established loci (rs2736100 at 5p15.33 and rs4488809 at 3q28) and a third at a recently reported locus (rs7216064 at 17q24.3).
Notably, there was no evidence for association across the 15q25 region, which has been associated with smoking-related lung cancer. There were also no strong association signals for other loci reported in either European or Asian populations.
The team then genotyped the most promising variants in an additional 1099 never-smoking women with lung cancer and 2913 healthy controls. This revealed three new susceptibility loci at 10q25.2 (rs7086803), 6q22.2 (rs9387478), and 6p21.32 (rs2395185).
The strongest of these loci, 10q25.2, maps to intron 7 of the VTI1A gene, which has been implicated in lung carcinogenesis, note the researchers.
Further analysis by histologic subtype showed that both the 6q22.2 (rs9387478) and 6p21.32 (rs2395185) loci were associated with adenocarcinoma only, which comprised 71% of cases, whereas the 10q25.2 (rs7086803) locus showed a somewhat larger effect for squamous carcinoma compared to adenocarcinoma.
"As the number of squamous carcinoma cases analyzed was small, we consider this a preliminary observation requiring independent replication," the authors caution.
They conclude: "Further work is warranted to map the new regions. Functional work is required to identify the variants that directly account for the underlying association, as well as to study how the genetic variants interact with established environmental risk factors, including environmental tobacco smoke, cooking fumes and fuel use, in never-smoking females in Asia."
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