Fish consumption, does it beneficially affect markers of colorectal carcinogenesis?

Background: Fish consumption is possibly associated with a decreased risk of colorectal cancer, as has been shown in several observational studies. However, most of these studies did not discriminate between the effects of oil-rich and lean fish. To date, no randomized controlled trials (RCTs) have examined the possible beneficial effects of fish intake on colorectal cancer risk. Aim: The aim of this thesis was to investigate whether fish consumption beneficially affects markers of colorectal carcinogenesis. Methods and Results: In a case control study (363 cases, 498 controls), we studied the association of serum n 3 polyunsaturated fatty acid (PUFA) levels as a marker of oil rich fish intake with colorectal adenomas, a precursor lesion of colorectal cancer. We found that individuals with high serum long chain n 3 PUFA levels had a decreased risk of colorectal adenomas (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.46; 0.96), whereas individuals with high serum n 6 PUFA levels had an increased risk of colorectal adenomas (OR 1.68, 95% CI 1.17; 2.42). In an RCT, we studied the effects of 3.5g/d fish oil (~1.5g/d n 3 PUFA) for 12 weeks on 19 serum inflammation markers in 77 healthy subjects and found that serum levels of these cytokines and chemokines were not changed. Finally, we studied the effects of increasing fish consumption compared with no additional fish, on markers of colorectal carcinogenesis in an RCT. Subjects (n=242), at an increased risk of colorectal cancer and those with no macroscopic signs of disease, were randomly allocated to receive dietary advice (DA) plus either two additional weekly portions of oil rich fish (salmon, ~1.4g/d n 3 PUFA) or lean fish (cod, ~0.09 g/d n 3 PUFA), or only DA for six months. We observed no change in apoptotic and mitotic cell numbers after the 6 months intervention with either salmon or cod compared with DA. Furthermore, colorectal genotoxicity, levels of cytokines and chemokines in colonic biopsies and feces, and fecal calprotectin were also not markedly changed after fish consumption. Only serum C reactive protein (CRP) levels were statistically significantly decreased after consumption of salmon ( 0.5 mg/l, 95% CI 0.9; 0.2) and cod ( 0.4 mg/l, 95% CI 0.7; 0.0) compared with DA. Conclusion: The results of this thesis do not provide strong evidence for beneficial effects of fish consumption on markers of colorectal carcinogenesis.