The association between body mass index, waist-to-hip ratio and an increase risk of post-menopausal breast cancer has been reported, but the mechanisms underlying this relationship are not fully understood. However, some evidence suggests that DNA methylation might be the reason for the association. For example, research1 published in the American Journal of Clinical Nutrition showed that in a case-case comparison of postmenopausal breast cancer cases, an increase in waist-to-hip ratio was associated with an increase in the chance of either E-cadherin, p16 or RAR-β2 genes undergoing promoter methylation. Promoter methylation for the E-cadherin, p16 or RAR-β2 genes was 20%, 25.9% and 27.5% respectively, but there was no association between DNA methylation and body mass index, waist-to-hip-ratio or lifetime weight changes in the control subjects. This suggests that the association between breast cancer and overweight individuals may in part be related to DNA methylation.
Just why waist-to-hip ratio might be associated with the promoter methylation of certain genes and increase the risk of breast cancer is not known. However, it has been speculated that this may relate to changes in the concentrations of circulating oestrogen that may in turn be altered by increases in the size of the adipose tissue storage. There is some evidence that oestrogen (particularly 17β-oestradiol in cell culture and rat models) and oestrogen related xenobiotic compounds (such as bisphenol A) can alter DNA methylation in breast tissue. Interestingly, the promoter methylation of E-cadherin, p16, BRCA1 and MLH1 have been shown to be associated with inflammation. This is interesting because obesity is now recognised to be a condition associated with chronic inflammation, and the possibility arises that it is the systemic inflammation associated with an increased waist-to-hip ratio that might cause the increase promoter methylation of breast cancer related genes.
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