Association Between SNPs in the One-Carbon Metabolism Pathway and the Risk of Female Breast Cancer in a Chinese Population

Xuhong Wang; Mengqiu Xiong; Bei Pan; William C S Cho; Jin Zhou; Shukui Wang; Bangshun He

doi:10.2147/PGPM.S328612

Association Between SNPs in the One-Carbon Metabolism Pathway and the Risk of Female Breast Cancer in a Chinese Population

Pharmgenomics Pers Med. 2022 Jan 11:15:9-16. doi: 10.2147/PGPM.S328612. eCollection 2022.

Authors

Xuhong Wang^#^{1

2}, Mengqiu Xiong^#², Bei Pan^{1

2}, William C S Cho³, Jin Zhou⁴, Shukui Wang^{1

2

5}, Bangshun He^{2

5}

Affiliations

¹ School of Medicine, Southeast University, Nanjing, Jiangsu Province, 210096, People's Republic of China.
² Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 210006, People's Republic of China.
³ Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China.
⁴ Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
⁵ Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Objective: The aim of this study is to assess the relationship between the single-nucleotide polymorphism (SNP) in the one-carbon metabolism pathway (MTR rs1805087; MTHFR rs1801133; ALDH1L1 rs2002287, rs2276731; DNMT1 rs16999593, rs2228611; DNMT3B rs2424908) and the risk of female breast cancer (BC) in a Chinese population.

Methods: A population-based case-control study was conducted, involving a total of 439 BC patients and 439 age-matched healthy controls. We adopted Sequence MASSarray to identify genotyping, and used immunohistochemistry (IHC) to test the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissue.

Results: We found that rs16999593 (TC/CC vs TT: adjusted OR=1.38, 95% CI: 1.03-1.84, p=0.030) was associated with an increased risk of BC, while rs2228611 was related to a decreased BC risk (GA/AA vs GG: adjusted OR=0.74, 95% CI: 0.56-0.97, p=0.030). In addition, stratified analysis revealed that DNMT1 rs16999593, rs2228611 and ALDH1L1 rs2002287 contributed to the risk of BC, with associations with ER, PR and HER-2 expression.

Conclusion: In summary, this study revealed that DNMT1 rs16999593 and rs2228611 were associated with BC risk.

Keywords: DNA methylation; DNMT1; SNP; breast cancer; one-carbon metabolism.

Grants and funding

This study was supported by The National Nature Science Foundation of China (no. 82073288), Jiangsu Youth Medical Talents Training Project to BH (QNRC2016066), and the Innovation Team of Jiangsu Provincial Health-Strengthening Engineering by Science and Education (CXTDB2017008).