Ratio of n-3/n-6 PUFAs and risk of breast cancer: a meta-analysis of 274135 adult females from 11 independent prospective studies

Background: Increased ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) in diet or serum may have a protective effect on the risk of breast cancer (BC); however, the conclusions from prospective studies are still controversial. The purpose of this study is to ascertain the relationship between intake ratio of n-3/n-6 PUFAs and the risk of BC, and estimate the potential summarized dose-response trend. Methods: Relevant English-language studies were identified through Cochrane Library, PubMed and EMBASE database till April 2013. Eligible prospective studies reporting the multivariate adjusted risk ratios (RRs) for association of n-3/n-6 PUFAs ratio in diet or serum with BC risk. Data extraction was conducted independently by 2 investigators; disagreements were reconciled by consensus. Study quality was assessed using the Newcastle-Ottawa scale. Study-specific RRs were combined via a random-effects model. Results: Six prospective nested case-control and 5 cohort studies, involving 8,331 BC events from 274,135 adult females across different countries, were included in present study. Subjects with higher dietary intake ratio of n-3/n-6 PUFAs have a significantly lower risk of BC among study populations (pooled RR = 0.90; 95% CI: 0.82, 0.99), and per 1/10 increment of ratio in diet was associated with a 6% reduction of BC risk (pooled RR = 0.94; 95% CI: 0.90, 0.99; P for linear trend = 0.012). USA subjects with higher ratio of n-3/n-6 in serum phospholipids (PL) have a significantly lower risk of BC (pooled RR = 0.62; 95% CI: 0.39, 0.97; I-2 = 0.00%; P for metaregression = 0.103; P for a permutation test = 0.100), and per 1/10 increment of ratio in serum PL was associated with 27% reduction of BC risk (pooled RR = 0.73; 95% CI: 0.59, 0.91; P for linear trend = 0.004; P for metaregression = 0.082; P for a permutation test = 0.116). Conclusions: Higher intake ratio of n-3/n-6 PUFAs is associated with lower risk of BC among females, which implies an important evidence for BC prevention and treatment is by increasing dietary intake ratio of n-3/n-6 PUFA. No firm conclusions from USA populations could be obtained, due to the limited numbers of USA studies.