Meta-analyses of lignans and enterolignans in relation to breast cancer risk

January 1, 2009 Human Health and Nutrition Data 0 Comments

Meta-analyses of lignans and enterolignans in relation to breast cancer risk

Year: 2009
Authors: Buck, K. Zaineddin, A.K. Vrieling, A. Linseisen, J. Chang-Claude, J.
Publication Name: Am. J. Clin. Nutr.
Publication Details: doi: 10.3945/ajcn.20089.28573.


Epidemiologic studies that examined whether lignans, the most important class of phytoestrogens in the Western diet, protect against breast cancer have yielded inconsistent results. In this study, we conducted meta-analyses on the association between lignans and breast cancer risk. We performed a systematic MEDLINE search to identify epidemiologic studies published between 1997 and August 2009. We calculated pooled risk estimates (REs) for total lignan exposure, dietary lignan intake, enterolignan exposure, and blood or urine concentrations of enterolactone and according to menopausal and estrogen receptor (ER) status of tumors. We included 21 studies (11 prospective cohort studies and 10 case-control studies) in the meta-analyses. Lignan exposure was not associated with an overall breast cancer risk (RE: 0.92; 95% CI: 0.81, 1.02; P heterogeneity = 0.004). However, in postmenopausal women, high lignan intake was associated with a significant reduced risk of breast cancer (13 studies; RE: 0.86; 95% CI: 0.78, 0.94; P heterogeneity = 0.32). Breast cancer risk was also inversely associated with enterolignan exposure (4 studies; RE: 0.84; 95% CI: 0.71, 0.97) but not with blood or urine enterolactone concentrations. The associations were not significantly different between ER-status subgroups (6 studies). High lignan exposure may be associated with a reduced breast cancer risk in postmenopausal women. Additional work is warranted to clarify the association between lignan exposure and breast cancer risk. (Authors abstract)
Breast cancer is the most common type of cancer worldwide and the most common cause of cancer death among women. Higher circulating estrogen concentrations have been associated with an increased risk of breast cancer. Phytoestrogens are plant-derived estrogen-like compounds that are able to bind to mammalian estrogen receptors (ERs) and may modulate estrogen metabolism by exerting an inhibitory effect on aromatase and, thereby, lower the amount of circulating estrogen in the body. Plant lignans are in high concentrations in flaxseeds and have been shown to have anti-carcinogenic properties. Lignans could have a protective effect on the development of breast cancer, but there is no clear evidence for an inverse association. Therefore, this meta-analyses was conducted on epidemiologic studies addressing lignans and breast cancer risk. The current evidence for an effect of high lignan intake compared with low lignan intake on breast cancer risk included 11 cohort (or nested case-control) and 10 case-control studies. Overall, no clear association between lignan exposure (dietary or biomarker assessment) and breast cancer risk was observed, and there was significant heterogeneity across studies. However, in postmenopausal women, a significant decreased breast cancer risk based on 13 studies was reported. The inverse association did not appear to be different for ER-positive and ER-negative tumors. It is possible that the mechanism by which lignans act may be effective only at low endogenous estradiol concentrations as shown in postmenopausal women. No differences in lignan effect according to ER status of tumors were found which supports proposed mechanisms of action including the reduction of angiogenesis and stimulation of apoptosis. Flaxseed was shown to be able to inhibit the proliferation of ER-positive and ER-negative tumor cells More studies assessing the effect modification by ER status are needed. Heterogeneity was shown to be significant when all studies and in some subgroups of the meta-analyses were considered. Generally, there was greater study heterogeneity for premenopausal women than for postmenopausal women, which, in part, might also be due to the smaller size of studies in premenopausal women. The large differences in lignan and enterolignan concentrations between the studies may be another source of heterogeneity.  Phytoestrogen-gene interactions may explain the conflicting results as they may modulate sex hormone�binding globulin and sex-hormone concentrations in postmenopausal women and interact with genetic variants involved in estrogen signaling pathways. Little is known regarding lignans and genetic polymorphisms in association with breast cancer risk. In conclusion, lignans were not significantly inversely associated with overall breast cancer risk. However, high lignan exposure, particularly high plant-lignan intake such as from flax,  was associated with a risk reduction especially in postmenopausal women. It remains unclear whether the effect of lignans on breast cancer risk differs by ER status of the tumor. Therefore, further studies are warranted to confirm the observed protective effect of lignan exposure on postmenopausal breast cancer risk, and to assess possible genetic modifying effects that could clarify the association between exposure to lignans and breast cancer risk. (Editors comments)

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