Are dietary factors involved in the association of CDH4 methylation and breast cancer risk?

摘要

DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits can alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell-cell adhesion glycoproteins. We conducted a case-control study (380 newly diagnosed BC and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL DNA), as well as its combined and interactive effects with dietary factors on BC risk. A case-only study (335 newly diagnosed BC) was conducted to analyse the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation was detected using quantitative methylation-specific PCR. Unconditional logistic regressions were used to analyse the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj) = 2 center dot 70, (95 % CI 1 center dot 90, 3 center dot 83), P < 0 center dot 001). CDH4 hypermethylation also showed significant combined effects with the consumption of vegetables (ORadj = 4 center dot 33, (95 % CI 2 center dot 63, 7 center dot 10)), allium vegetables (ORadj = 7 center dot 00, (95 % CI 4 center dot 17, 11 center dot 77)), fish (ORadj = 7 center dot 92, (95 % CI 3 center dot 79, 16 center dot 53)), milk (ORadj = 6 center dot 30, (95 % CI 3 center dot 41, 11 center dot 66)), overnight food (ORadj = 4 center dot 63, (95 % CI 2 center dot 69, 7 center dot 99)), pork (ORadj = 5 center dot 59, (95 % CI 2 center dot 94, 10 center dot 62)) and physical activity (ORadj = 4 center dot 72, (95 % CI 2 center dot 87, 7 center dot 76)). Moreover, consuming milk was significantly related with decreased risk of CDH4 methylation (OR = 0 center dot 61, (95 % CI 0 center dot 38, 0 center dot 99)) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

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