Marine ω-3 polyunsaturated fatty acids and risk for colorectal cancer according to microsatellite instability

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

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38 Citations (Scopus)


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 documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. All statistical tests were two-sided. Results: Marine ω-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P heterogeneity =. 02): High marine ω-3 PUFA intake was associated with a lower risk for MSI-high tumors (comparing 0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P linearity =. 03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P linearity =. 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 for 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.

Original languageEnglish
JournalJournal of the National Cancer Institute
Issue number4
Publication statusPublished - 2015 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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