[Association between KLK10 gene methylation in female breast tumor tissue and the risk of invasive breast cancer].

<b>Objective:</b> To explore the association between human kallikrein 10 (KLK10) gene methylation levels in female breast tumor tissues and risk of invasive breast cancer. <b>Methods:</b> A case-control study was conducted. The clinical data and paraffin-embedded breast tissue samples of female patients with invasive breast cancer and benign breast diseases admitted to Huai'an Hospital Affiliated to Xuzhou Medical University from 2017 to 2020 and to the Affiliated Hospital of Nantong University from 2020 to 2021 were retrospectively collected, and the methylation levels of each CpG site of the KLK10 gene in the tissues were detected. The methylation levels of KLK10 gene were compared between benign breast diseases and invasive breast cancer (including different pathological types and molecular subtypes), and the multivariate logistic regression model was used to analyze the correlation between the methylation level of KLK10 gene CpG site and the risk of invasive breast cancer. The <i>OR</i> value was expressed as the relative risk of invasive breast cancer for each 10% increase in methylation level. <b>Results:</b> A total of 462 cases of invasive breast cancer aged 52 (46, 58) years and 517 benign breast disease controls aged 45 (41, 50) years were collected. The methylation levels of KLK10_CpG_1 [0.41 (0.26, 0.59) vs 0.36 (0.24, 0.50)], KLK10_CpG_3 [0.38 (0.18, 0.61) vs 0.32 (0.19, 0.49)], and KLK10_CpG_4 [0.52 (0.39, 0.65) vs 0.30 (0.22, 0.38] in the invasive breast cancer group were higher than those in the benign control group (all <i>P</i><0.05). There were significant differences in the methylation levels of KLK10_CpG_1, KLK10_CpG_3 and KLK10_CpG_4 between the benign control group and various pathological types and molecular subtypes of invasive breast cancer (all <i>P</i><0.05). The methylation levels of KLK10_CpG_4 in all different pathological types and molecular subtypes of breast cancer were higher than those in the control group (all <i>P</i><0.05). The methylation levels of the overall KLK10_CpG_1 (<i>OR</i>=1.10, 95%<i>CI</i>: 1.03-1.17), KLK10_CpG_3 (<i>OR</i>=1.11, 95%<i>CI</i>: 1.05-1.18), and KLK10_CpG_4 (<i>OR</i>=1.77, 95%<i>CI</i>: 1.61-1.95) sites were positively correlated with invasive breast cancer (all <i>P</i><0.05). In breast cancer patients aged≤50 years, the methylation levels of KLK10_CpG_1 (<i>OR</i>=1.14, 95%<i>CI</i>: 1.05-1.24), KLK10_CpG_3 (<i>OR</i>=1.12, 95%<i>CI</i>: 1.04-1.21) and KLK10_CpG_4 (<i>OR</i>=1.90, 95%<i>CI</i>: 1.68-2.15) sites were positively correlated with invasive breast cancer (all <i>P</i><0.05). In breast cancer patients aged>50 years, the high methylation levels of KLK10_CpG_3 (<i>OR</i>=1.13, 95%<i>CI</i>: 1.03-1.25) and KLK10_CpG_4 (<i>OR</i>=1.60, 95%<i>CI</i>: 1.37-1.86) sites were positively correlated with invasive breast cancer (all <i>P</i><0.05). <b>Conclusion:</b> Hypermethylation of the KLK10 gene in female breast tumor tissue is associated with the risk of invasive breast cancer.