Intake of fish and marine n3 polyunsaturated fatty acids and risk of breast cancer: metanalysis of data from 21 independent prospective cohort studies

To investigate the association between intake of fish and n3 polyunsaturated fatty acids (n3 PUFA) and the risk of breast cancer and to evaluate the potential dose response relation. Meta analysis and systematic review of prospective cohort studies. PubMed and Embase up to December 2012 and references of retrieved relevant articles. Prospective cohort studies with relative risk and 95 percent  confidence intervals for breast cancer according to fish intake, n3 PUFA intake, or tissue biomarkers. Twenty six publications, including 20 905 cases of breast cancer and 883 585 participants from 21 independent prospective cohort studies were eligible. Eleven articles (13 323 breast cancer events and 687 770 participants) investigated fish intake, 17 articles investigated marine n3 PUFA (16 178 breast cancer events and 527 392 participants), and 12 articles investigated alpha linolenic acid (14 284 breast cancer events and 405 592 participants). Marine n3 PUFA was associated with 14 percent reduction of risk of breast cancer (relative risk for highest v lowest category 0.86 (95 percent  confidence interval 0.78 to 0.94), I2 equal 54), and the relative risk remained similar whether marine n3 PUFA was measured as dietary intake (0.85, 0.76 to 0.96, I2 equal 67percent ) or as tissue biomarkers (0.86, 0.71 to 1.03, I2 equal 8 percent ). Subgroup analyses also indicated that the inverse association between marine n3 PUFA and risk was more evident in studies that did not adjust for body mass index (BMI) (0.74, 0.64 to 0.86, I2 equal 0) than in studies that did adjust for BMI (0.90, 0.80 to 1.01, I2 equal 63.2percent ). Dose-response analysis indicated that risk of breast cancer was reduced by 5 percent  per 0.1g/day (0.95, 0.90 to 1.00, I2 equal 52 percent ) or 0.1percent  PUFA intake. No significant association was observed for fish intake or
exposure to alpha linolenic acid. Higher consumption of dietary marine n3 PUFA is associated with a lower risk of breast cancer. The associations of fish and alpha linolenic acid intake with risk warrant further investigation of prospective cohort studies. These findings could have public health implications with regard to prevention of breast cancer through dietary and lifestyle interventions. (Authors abstract)

Breast cancer is one of the most common cancers and the leading cause of death from cancer among women, accounting for 23 percent  of the total cancer cases and 14 percent  of cancer deaths in 2008. Several large prospective cohort studies have suggested an inverse association between dietary n3 PUFA intake and risk. Furthermore, several case control studies have indicated that n3 PUFA, measured as either dietary intake or with tissue biomarkers, is inversely associated with risk. A meta analysis was conducted to summarise the associations between dietary intake of fish and n3 PUFA with incident breast cancer based on prospective cohort studies. Risk estimates were pooled for the highest versus lowest category of intake (or tissue biomarkers) across identified prospective cohort studies to examine the overall association. A dose response analysis for the trend estimation and a stratified analysis to examine the sources of heterogeneity was conducted. In this meta analysis dietary intake of marine n3 polyunsaturated fatty acids (PUFA), but not alpha linolenic acid (ALA), was associated with a lower risk of breast cancer. Fish consumption was not associated with risk. Dose response analyses indicated a 5 percent lower risk of breast cancer per 0.1g/day or 0.1 percent  energy/day increment of dietary marine n3 PUFA, but no significant trend for ALA or fish intake. ALA and  fish intake in western populations might be too low to detect a protective effect. The effect of ALA on breast tumour growth is less clear, and no significant association was reported. The explanation for the inconsistency among studies regarding dietary ALA and risk of breast cancer could be the different dietary sources. Dietary ALA from fruit and vegetables and vegetable oils has been shown to be inversely associated with risk but a positive association for ALA from nut mixes and processed meat is noted.  The meta analysis does have several  limitations.  Firstly, different methods of assessment (diet and tissue biomarker) were used in the included studies, and the units were heterogeneous across different studies. Secondly, available data on the individual n3 PUFA is rather limited. Therefore, future prospective studies are needed for the detailed analysis of association between individual n3 PUFA and risk of breast cancer. Thirdly, the observational nature of the included studies makes it subject to the influence of residual confounders.  Evidence from either experimental or observational studies suggests a protective effect of marine n3 PUFA on breast cancer, though no conclusive results have been achieved. The protective effect of fish or individual n3 PUFA warrants further investigation of prospective studies. (Editors comments)