Abstract 1879: Prospective study of marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability

Abstract

Abstract Background: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive. Methods: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses’ Health Study and Health Professionals Follow-up Study. We collected updated data on marine ω-3 PUFA intake and documented 1,125 CRC cases during 24-26 years of follow-up. We determined the MSI status of tumors using 10 microsatellite markers, and classified cases into MSI-high tumors in which ≥30% of the microsatellite markers demonstrated instability, and microsatellite stable (MSS) tumors in which <30% of the markers demonstrated instability. Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of microsatellite stable (MSS) tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. Results: There was no statistically significant association between marine ω-3 PUFA intake and overall incidence of CRC. However, a statistically significant difference was detected by MSI status (Pheterogeneity = 0.02): high marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d to <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P for linearity = 0.03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P for linearity = 0.28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status. Conclusions: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms. Citation Format: Mingyang Song, Reiko Nishihara, Kana Wu, Zhi Rong Qian, Sun A. Kim, Yasutaka Sukawa, Kosuke Mima, Kentaro Inamura, Atsuhiro Masuda, Juhong Yang, Charles S. Fuchs, Edward L. Giovannucci, Shuji Ogino, Andrew T. Chan. Prospective study of marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1879. doi:10.1158/1538-7445.AM2015-1879