Interaction between CYP3A4 gene polymorphism and obesity on breast cancer susceptibility in Chinese women.

Jiamin ZHU; Xiaogang ZHAI; Feng NI; Cheng TAN; Yun GUAN; Baixia YANG; Jing CAI

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Interaction between CYP3A4 gene polymorphism and obesity on breast cancer susceptibility in Chinese women.

Author: Jiamin ZHU ¹ ; Xiaogang ZHAI ² ; Feng NI ² ; Cheng TAN ² ; Yun GUAN ² ; Baixia YANG ² ; Jing CAI ³
Author Information

1. Department of Oncology, the Affiliated Jiangyin Hospital of Nantong University.
2. Department of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University.
3. Department of Radiotherapy, Nantong Rici Hospital Affiliated to Yangzhou University.
Publication Type:Journal Article
Keywords: Breast cancer; CYP3A4; Cytochrome P450; Haplotype; Interaction; Obesity; SNP
MeSH: Adult; Aged; Female; Humans; Middle Aged; Breast Neoplasms/etiology*; China/epidemiology*; Cytochrome P-450 CYP3A/metabolism*; Gene-Environment Interaction; Genetic Predisposition to Disease; Haplotypes; Obesity/epidemiology*; Polymorphism, Single Nucleotide; Risk Factors; East Asian People
From:Environmental Health and Preventive Medicine 2025;30():88-88
CountryJapan
Language:English
Abstract: BACKGROUND:To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women.
METHODS:Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform.
RESULTS:Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk.
CONCLUSIONS:We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.