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. 2015 Mar 25;107(4):djv007.
doi: 10.1093/jnci/djv007. Print 2015 Apr.

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

Mingyang Song  1 , Reiko Nishihara  1 , Kana Wu  1 , Zhi Rong Qian  1 , Sun A Kim  1 , Yasutaka Sukawa  1 , Kosuke Mima  1 , Kentaro Inamura  1 , Atsuhiro Masuda  1 , Juhong Yang  1 , Charles S Fuchs  1 , Edward L Giovannucci  1 , Shuji Ogino  1 , Andrew T Chan  1
Affiliations

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

Mingyang Song et al. J Natl Cancer Inst. .

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 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 of 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 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.

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Figures

Figure 1.
Figure 1.
Restricted cubic spline plot for marine ω-3 PUFA intake in relation to risk of MSS and MSI-high colorectal cancers in the pooled cohorts of the Nurses’ Health Study (1984–2010) and Health Professionals Follow-up Study (1986–2010). Dash and hatched lines represent 95% confidence intervals. Multivariable model was adjusted for the same set of covariables as in Table 2. No spline variable was selected. P linearity = .03 for MSI-high tumors and .28 for MSS tumors. All P values are two-sided. MSI = microsatellite instability; MSS = microsatellite-stable; PUFA = polyunsaturated fatty acids.
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