Joint effects of WT1, CA10 methylation in peripheral blood leukocyte and dietary zinc on breast cancer risk: a case-control study

Abstract

Background Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with elevated risk of cancer. However, associations between the methylation of zinc-related genes, WT1 and CA10, and breast cancer risk, and interactions between WT1, CA10 methylation and dietary zinc intake on breast cancer risk remain unknown. Methods The methylation of WT1, CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N = 959). Logistic regression was used to analyze the associations and propensity score (PS) method was used to adjust confounders. Results The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer with an odds ratio (OR) of 3.069 [95% confidence interval (CI): 1.669–5.643, P < 0.001]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of Luminal A subtype (OR = 2.620, 95%CI: 1.107-6.200, P = 0.029) and Luminal B subtype (OR = 3.231, 95%CI: 1.339–7.796, P = 0.009). CA10 hypermethylation was associated with an increased risk of Luminal B subtype (OR = 1.798, 95%CI: 1.085–2.982, P = 0.023). Furthermore, the joint effects of methylation of WT1, CA10 and lower dietary zinc intake were associated a strongly elevated risk of breast cancer with ORs of 11.220 (95%CI: 4.057–31.032, P < 0.001) and 4.145 (95%CI: 2.717–6.324, P < 0.001), respectively. Conclusion The study suggested the hypermethylation of WT1 methylation in leukocytes was significantly associated with an increased risk of breast cancer. Notably, the joint effects of WT1, CA10 methylation and lower dietary zinc intake might significantly associate with breast cancer risk.