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

Jones, C. C.; Bradford, Y.; Amos, C. I.; Blot, W. J.; Chanock, S. J.; Harris, C. C.; Schwartz, A. G.; Spitz, M. R.; Wiencke, J. K.; Wrensch, M. R.; Wu, X.; Aldrich, M. C.

doi:10.1101/405035

bioRxiv · 10.1101/405035

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

Jones, C. C.·Bradford, Y.·Amos, C. I.·Blot, W. J.·Chanock, S. J.·Harris, C. C.·Schwartz, A. G.·Spitz, M. R.·Wiencke, J. K.·Wrensch, M. R.·Wu, X.·Aldrich, M. C.

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Abstract

BackgroundIdentifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European descent individuals. Yet population-specific genetic variation can occur and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans.\n\nMethodsWe conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status.\n\nResultsWe identified three novel genomic regions significantly associated (FDR-corrected p-value < 0.10) with lung cancer risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and rs11658063 on 17q12). On chromosome16q22.2, rs7186207 was significantly associated with increased risk (OR=1.24, 95% CI: 1.12-1.38) and functional annotation using GTEx showed rs7186207 modifies DHODH gene expression. The risk allele at rs336958 on 5q14.3 was associated with reduced lung cancer risk (OR=0.68, 95% CI: 0.56-0.82), while the risk allele at rs11658063 on 17q12 was associated with increased risk (OR=1.24, 95% CI: 1.11-1.39).\n\nConclusionWe identified novel associations on chromosomes 5q14.3, 16q22.2, and 17q12, which contain HNF1B, DHODH, and HAPLN1 genes, respectively. SNPs within these regions have been previously associated with multiple cancers. This is the first study to examine cross-cancer pleiotropic associations for lung cancer in African Americans.\n\nImpactOur findings demonstrate novel cross-cancer pleiotropic associations with lung cancer risk in African Americans.

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Jones, C. C., Bradford, Y., Amos, C. I., Blot, W. J., Chanock, S. J., Harris, C. C., Schwartz, A. G., Spitz, M. R., Wiencke, J. K., Wrensch, M. R., Wu, X., Aldrich, M. C.. 2018-08-31. Cross-cancer pleiotropic associations with lung cancer risk in African Americans. https://doi.org/10.1101/405035

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