Abstract 2926: Effect of common cancer susceptibility variants on risk of second primary cancers: results from the Multiethnic Cohort and PAGE studies

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Second primary cancers (SPC) account for approximately 16% of all incident cancers in the U.S. Genome-wide associations studies (GWAS) have identified over one hundred-fifty genetic variants associated with different cancer sites. A few of these SNPs, such as rs6983267 on chromosome 8q24, have been associated with multiple cancer sites. However, the association of cancer risk variants with the occurrence of second primary cancers has not been investigated. As part of the Population Architecture using Genomics and Epidemiology (PAGE) consortium, using data from the Multiethnic Cohort Study (MEC), we investigated the association of 148 cancer risk variants with the risk of SPC. Persons with SPC (n=666) were defined as cohort members diagnosed with >1 incident cancers after cohort entry. Two sets of controls were selected for this analysis: i) single-index cancer controls (n=9,195): participants who had a single incident cancer of the same site as the case after cohort entry, ii) cancer-free controls (n=8,974): participants who remained cancer-free at end of follow-up. Tests of main effects for each SNP were conducted using unconditional logistic regression, assuming a genetic log-additive model, and were adjusted for age at primary cancer, sex and race/ethnicity. When using single-index cancer controls, models were also adjusted for stage and site of the primary cancer. Analyses using cancer-free controls showed 15 of 148 SNPs associated with risk of SPC (p<0.05): 5 prostate cancer SNPs, 3 breast cancer SNPs, 3 lung cancer and/or nicotine dependence SNPs, 1 colorectal cancer SNP, 1 melanoma SNP, 1 basal cell carcinoma SNP, and 1 glioma SNP. Twelve SNPs were positively and 3 SNPs inversely associated with risk. The associations for four of these 15 SNPs remained statistically significant (p<0.05) even after using single-index cancer controls and adjusting for stage and site of the primary cancer. These four SNPs were previously found to be associated with glioma (CCDC26 rs10464870, OR: 1.22, 95% CI: 1.05, 1.41); basal cell carcinoma (CDKN2BAS rs2151280, OR: 1.15, 95% CI: 1.02, 1.30); lung cancer/nicotine dependence (CTNNA3 rs4142041, OR: 0.81, 95% CI: 0.71, 0.93); and melanoma (MC1R rs4785763, OR: 1.18, 95% CI: 1.03, 1.35). In addition, when using these single-index cancer controls, we also found an association with a testicular germ cell tumor SNP (CENPE/TACR3 rs4699052, OR: 0.87, 95% CI: 0.77, 0.99). However, none of these associations remained statistically significant after Bonferroni correction for multiple comparisons. No heterogeneity across race/ethnicity was observed. Replications are ongoing in other PAGE cohorts. In conclusion, site-specific cancer risk variants may be associated with risk of SPC, suggesting common biological pathways in subsequent cancer development among cancer survivors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2926. doi:1538-7445.AM2012-2926