Cross-cancer pleiotropic associations with lung cancer risk in African Americans

Abstract

Background: Identifying genetic variants with pleiotropic rs11658063 on 17q12). On chromosome16q22.2, rs7186207 associations across multiple cancers can reveal shared biologic was significantly associated with reduced risk [OR ¼ 0.43; 95% pathways. Prior pleiotropic studies have primarily focused on confidence interval (CI), 0.73–0.89], and functional annota-European-descent individuals. Yet population-specific genetic tion using GTEx showed rs7186207 modifies DHODH gene variation can occur, and potential pleiotropic associations expression. The minor allele at rs336958 on 5q14.3 was among diverse racial/ethnic populations could be missed. We associated with increased lung cancer risk (OR ¼ 1.47; 95% examined cross-cancer pleiotropic associations with lung can-CI, 1.22–1.78), whereas the minor allele at rs11658063 on cer risk in African Americans. 17q12 was associated with reduced risk (OR ¼ 0.80; 95% CI, Methods: We conducted a pleiotropic analysis among 1,410 0.72–0.90). African American lung cancer cases and 2,843 controls. We Conclusions: We identified novel associations on chromo-examined 36,958 variants previously associated (or in linkage somes 5q14.3, 16q22.2, and 17q12, which contain HNF1B, disequilibrium) with cancer in prior genome-wide association DHODH, and HAPLN1 genes, respectively. SNPs within these studies. Logistic regression analyses were conducted, adjusting regions have been previously associated with multiple cancers. for age, sex, global ancestry, study site, and smoking status. This is the first study to examine cross-cancer pleiotropic Results: We identified three novel genomic regions signif-associations for lung cancer in African Americans. icantly associated (FDR-corrected P <0.10) with lung cancer Impact: Our findings demonstrate novel cross-cancer pleio-risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and tropic associations with lung cancer risk in African Americans.