Abstract 2187: Colorectal cancer survival is not associated with genetic variants related to risk of other cancers: The GECCO study

Abstract

Abstract Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality. Previous genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms (SNPs) associated with CRC, at least one of which has also been found to be associated with CRC survival. Furthermore, some SNPs have demonstrated risk associations with multiple cancers (i.e. pleiotropy), including CRC. Together, this raises the possibility that SNPs associated with risk of other cancers may also be associated with survival after a diagnosis of CRC. To investigate this question, we evaluated 526 SNPs reported as strongly associated with risk of any type of cancer in the National Human Genome Research Institute GWAS catalog (as of 11/13/2013) for an association with CRC-specific and overall survival. This study utilized data available from multiple studies in the Genetic Epidemiology of Colorectal Cancer Consortium (GECCO). Methods: We evaluated 526 SNPs associated with risk of cancers other than CRC in six studies participating in GECCO: the Health Professionals Follow-up Study; the Nurses' Health Study; the Physicians' Health Study; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; the VITamins And Lifestyle Study; and the Women's Health Initiative. A total of 3,494 colorectal cancer cases were evaluated, of whom 1,223 (35%) died (830 from CRC, 24%) during follow-up (average median follow-up time of 6.8 years). Cox proportional hazards regression was used to calculate the per-allele hazard ratio (HR) and 95% confidence interval (95% CI) for the association between each SNP and CRC-specific or overall survival, adjusting for age at diagnosis, sex, study sample, and the first three principal components of genetic ancestry. Results: After Bonferroni correction for multiple comparisons (P = 0.05/526 = 9.51e-5), no SNPs were statistically significantly associated with either CRC-specific or overall survival. For CRC-specific survival, 35 SNPs showed a nominal association (p<0.05), the strongest being breast cancer SNP rs6504950 in STXBP4 (HR = 1.19, 95% CI = 1.06-1.31, p = 0.0018). For overall survival, 38 SNPs showed a nominal association, the strongest being melanoma SNP rs1393350 in TYR (HR = 1.15, 95% CI = 1.06-1.26, p = 0.0012). More SNPs showed a nominal association with survival than expected by chance (0.05*526 = 26 SNPs). Conclusion: These preliminary results broadly suggest that CRC-specific and overall survival do not appear to be strongly associated with genetic variants related to incidence for other cancers. However, some suggestive evidence of nominal associations with survival supports further investigation. Planned future steps include the incorporation of two additional studies (Cancer Prevention Study II; Diet, Activity, and Lifestyle Study), as well as analyses stratified by factors such as cancer site, stage at diagnosis, and sex. Citation Format: Jonathan M. Kocarnik, Michael N. Passarelli, Amanda I. Phipps, Andrew T. Chan, Manish Gala, Amit Joshi, Peter T. Campbell, Martha L. Slattery, John Potter, Emily White, Sonja Berndt, Ulrike Peters, Polly A. Newcomb. Colorectal cancer survival is not associated with genetic variants related to risk of other cancers: The GECCO study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2187. doi:10.1158/1538-7445.AM2014-2187