Breast Cancer Risk Variant Associated With Increased Lung Cancer Risk in Women
In a study reported in the Journal of the National Cancer Institute, Park et al examined single nucleotide polymorphisms (SNPs) associated with other cancers for potential associations with lung cancer. They found that the breast cancer SNP LSP1 rs3817198 was associated with significant risk of lung cancer, and particularly adenocarcinoma, in women.
Study Details
The study involved data from 18,023 patients with lung cancer and 60,543 control subjects from 13 studies included in the Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL) consortia. A total of 165 SNPs associated with ≥ 1 of 16 non–lung cancer sites were examined for association with lung cancer. A Bonferroni-corrected P value of 2.5×10-5 was set as statistical significance to adjust for multiple comparisons.
A total of 15 SNPs were nominally associated with lung cancer at P < .05, including eight variants for prostate cancer variants, four for glioma, one for breast cancer, one for childhood acute lymphocytic leukemia, and one for follicular lymphoma variant. No heterogeneity by race/ethnicity was noted for the 15 nominally associated SNPs and only two associations were heterogeneous by smoking status.
Breast Cancer Variant
The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.05–1.14) and remained significant (P = 2.8×10–6) after correction for multiple comparisons. The association was heterogeneous for cell type (P = .03) and sex (P = .01).
In particular, the association appeared to be limited to adenocarcinoma (OR = 1.11, P = 1.14×10–4) and women (OR = 1.16, P = 4.31×10–6). The association was not observed for squamous cell carcinoma or small cell carcinoma or in men (P = .16). Stratified analysis by both sex and histology cell type among studies with available data showed an association for female adenocarcinoma (OR = 1.19, P = 1.2×10–4) and not for male adenocarcinoma (P = .14), although the test for heterogeneity of effect for adenocarcinoma by sex was not significant (P = .10).
Glioma Variants
The glioma risk variant TERT rs2853676 was nominally associated with overall lung cancer (P = .001) but significantly associated with adenocarcinoma (OR = 1.16, P = 1.1×10–8). The SNP was not associated with either squamous cell or small cell carcinoma. The association was attenuated in analysis conditioned on a known TERT risk variant among studies with available data (OR = 1.06, P = .09), but remained significant on meta-analysis of these studies without conditioning for the known risk variant (OR = 1.16, P = 1.3 × 10–7).
The glioma risk variant CDKN2BAS1 rs4977756, also located in a region previously associated with lung cancer, was not associated with overall lung cancer risk (P = .13) but was significantly associated with risk for squamous cell carcinoma (OR = 1.11, P = 2.5×10–5). The SNP was not associated with adenocarcinoma or small cell carcinoma. Independent effects between the SNP and the previously reported lung cancer risk variant could not be determined due to the small subset of data available for the latter.
The investigators concluded, “Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk…. Our results support the influence of non–lung cancer risk variants on the risk of lung cancer, and these associations may differ by histological cell type and sex. Molecular studies are needed to better characterize these genetic effects and to increase our understanding of the apparent heterogeneity of effects across sex and histological cell type.”
S. Lani Park, PhD, MPH, of University of Southern California Keck School of Medicine, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by the Population Architecture Using Genomics and Epidemiology program, which is funded by the National Human Genome Research Institute.
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