Effect of a fish intervention on markers of colorectal carcinogenesis: the FISHGASTRO study

Several observational studies have indicated that fish consumption is inversely associated with the occurrence of colorectal adenomas and progression of ulcerative colitis (UC), both risk factors for colorectal cancer. N-3 fatty acids in oily fish may favourably influence inflammatory processes involved in colorectal carcinogenesis. Also, other constituents of fish, such as vitamin D and selenium may be involved. It is unknown whether the protective effect of fish is associated only with the consumption of oil-rich fish or also with lean fish consumption. Until now no intervention studies on fish and gastrointestinal health have been performed. The aim of FISHGASTRO is to assess whether oily and/or lean fish consumption reduces the risk of intermediates of colorectal cancer as assessed by mitotic rate, apoptosis, and crypt length in colonic biopsies. The study is a randomised, parallel, multi-centre six months intervention trial. In total, 242 volunteers were randomly allocated to receive one of three interventions: oil-rich fish (salmon) (n=82), lean fish (cod) (n=78), or no extra fish (n=82). Colonic biopsies were collected before and after the six month intervention. Results were analysed using analysis of covariance (ANCOVA) including baseline values of the studied measure. Preliminary results show that after intervention, the number of mitotic cells per crypt was more reduced, although not statistically significant, after intervention with salmon (-1.44 ±3.16) or cod (-1.53 ±3.66) compared to the dietary advice group (-0.83 ±2.50). Colonic apoptosis rates per crypt were less reduced in the salmon (-0.12 ±0.69) and cod group (-0.01 ±0.86, p=0.06) compared to the dietary advice group (-0.21 ±0.59). Crypt length was more reduced in the salmon (0.3 ±3.4) and cod group (1.0 ±3.8), compared to the dietary advice group (2.0 ±12.3). Although results from this study were not statistically significant, they do show a trend that increased fish consumption can contribute to lower mitotic and apoptosis rates, and shorter crypt length, which are all indicators of a reduced colorectal cancer risk. Additional analyses on gene expression and inflammation are ongoing.The work was performed within Integrated Project SEAFOODplus, granted by the European Union (EU-506359), www.seafoodplus.org .