A comprehensive meta-analysis on dietary flavonoid and lignan intake and cancer risk: Level of evidence and limitations.

SCOPE To summarize available evidence on the association between dietary flavonoid as well as lignan intake and cancer risk in observational studies. METHODS AND RESULTS A systematic search on electronic databases of all English language case-control and prospective studies published up to June 2016 was performed. Risk ratios (RRs) and 95% confidence intervals were calculated by random-effects model separately by study design. Heterogeneity and publication bias were tested. Out of the 143 studies included, meta-analyses of prospective studies showed isoflavones significantly associated with decreased risk of lung and stomach cancers and nearly significant breast and colorectal cancers; total flavonoids showed nonsignificant decreased risk of breast cancer. Meta-analyses of case-control studies showed: total and/or individual classes of flavonoids associated with upper aero-digestive tract, colorectal, breast, and lung cancers; isoflavones with ovarian, breast, and colorectal cancers, endometrial and lung cancers. CONCLUSIONS Most evidence reported in previous meta-analyses was driven by case-control studies. Overall results may be promising but are inconclusive. Further prospective cohorts assessing dietary polyphenol exposure and studies using other methods to evaluate exposure (i.e. markers of consumption, metabolism, excretion) are needed to confirm and determine consumption levels required to achieve health benefits.