Modified risk of breast cancer by dietary factors and HS3ST2 methylation

Abstract Background: DNA methylation, which has been demonstrated to be influenced by dietary factors, is associated with changes in breast cancer (BC) risk and clinicopathological features.Methods: A case-control study (271 newly diagnosed cases, 326 controls) was conducted to evaluate the effect of dietary factors and HS3ST2 methylation in peripheral blood leukocyte DNA on the risk of BC. Moreover, a case-only study (298 cases) was designed to evaluate the effects of dietary factors on HS3ST2 methylation in tumor tissue and the relationship of methylation with clinicopathological features.Results: The dietary consumption of fruit, poultry, marine fish, milk, and pork and regular exercise was significantly associated with changes in the risk of BC. We also found a significant association between HS3ST2 hypermethylation and BC risk (odds ratio [OR] = 1.618, 95% confidence interval [CI] = 1.077–2.243). The combined effects of HS3ST2 hypermethylation and lower fruit intake (<500 vs. ≥500 g/week, OR = 2.553, 95% CI = 1.328–4.908), poultry (<1 vs. ≥1/week, OR = 3.197, 95% CI = 1.598– 6.385), marine fish (<1 vs. ≥1 time/month, OR = 4.272, 95% CI = 2.117–8.621), and milk (<3 vs. ≥3 times/week, OR = 6.072, 95% CI = 2.399–15.568) and irregular exercise (<1 vs. ≥1 time/week, OR = 4.149, 95% CI = 1.908–9.022) were significantly associated with an increased risk of BC. The consumption of canned meat was associated with the hypermethylation status of HS3ST2 in BC tissues (OR = 3.884, 95% CI = 1.078–13.991). HS3ST2 hypermethylation was significantly associated a basal-like status (vs. luminal A, OR = 1.981, 95% CI = 1.036–3.787) and estrogen receptor negativity (Negative vs. Positive, OR = 1.744, 95%CI = 1.053-2.887) in BC tissues and TNM stages II–IV (II–IV vs. I, OR = 1.692, 95% CI = 1.040–2.752) in peripheral blood leukocyte DNA. Conclusion: Maintaining healthy dietary habits is of great significance for preventing BC, especially for women with HS3ST2 hypermethylation.