Novel Genetic Susceptibility Markers for Breast Cancer in Iraqi Women: First Evidence of CYP3A4*1B Protective Effects and GSTP1/MTHFR Risk Associations

IF 2.7 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2026-03-01 Epub Date: 2025-10-13 DOI:10.1016/j.clbc.2025.10.004

Wisam Hindawi Hoidy , Mohammed Ouda Orabiy , Shaimaa Mohsen Essa , Layth Samir Jasim

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引用次数: 0

Abstract

Background

This is the first study looking at breast cancer risk using the polymorphisms CYP3A4*1B, GSTP1 Ile105Val, MTHFR C677T, and COMT Val158Met for breast cancer predisposed Iraqi population with specific environmental carcinogenic exposures.

Methods

Aged matched healthy controls were 610 individuals of Iraqi origin alongside 414 histologically confirmed breast cancer patients forming a case-control study cohort. CDNA was obtained from peripheral blood samples, which underwent genotyping via tetra-primer ARMS-PCR. Statistical evaluation was performed based on several genetic models with odds ratios (OR) and 95% confidence intervals (CI) calculated by logistic regression.

Results

For 3 polymorphisms, crucial associations were found and these include CYP3A4*1B which showed a protective effect against breast cancer (OR = 0.72, 95% CI, 0.54-0.96, P = .027), the effect being strong in women less than 50 years old. Increased cancer risk was associated with GSTP1 Ile105Val (OR = 1.68, 95% CI, 1.23-2.31, P = .001) especially in older females and those with elevated BMI. The same risk was also conferred by MTHFR C677T (OR = 1.45; 95% CI, 1.12-1.89, P = .005). No significant association for COMT Val158Met was observed (P = .156). All polymorphisms among controls were in Hardy–Weinberg equilibrium.

Conclusions

The study presented the taw evidence of both CYP3A4*1B and GSTP1 Ile105Val along with MTHFR C677T polymorphisms associating them to breast cancer susceptibility in Iraqi population which reflects these specific genetic risks and reinforces middle eastern populations towards precision medicine frameworks concerning breast cancer treatment and intervention strategies.

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伊拉克妇女乳腺癌的新遗传易感性标记：CYP3A4*1B保护作用和GSTP1/MTHFR风险关联的第一个证据

背景：这是第一项利用CYP3A4*1B、GSTP1 Ile105Val、MTHFR C677T和COMT Val158Met多态性对乳腺癌易感伊拉克人群进行乳腺癌风险研究，这些人群具有特定的环境致癌暴露。方法：年龄匹配的健康对照是610名伊拉克裔个体和414名组织学证实的乳腺癌患者，形成病例对照研究队列。采用四引物ARMS-PCR对外周血样本进行基因分型。采用logistic回归计算优势比（OR）和95%置信区间（CI），根据几种遗传模型进行统计评价。结果：在3个多态性中，发现了关键的关联，其中CYP3A4*1B显示出对乳腺癌的保护作用（OR = 0.72, 95% CI, 0.54-0.96, P = 0.027），在50岁以下的女性中效果较强。癌症风险增加与GSTP1 Ile105Val相关（OR = 1.68, 95% CI, 1.23-2.31, P = .001），特别是在老年女性和BMI升高的人群中。MTHFR C677T也有相同的风险（OR = 1.45; 95% CI, 1.12-1.89, P = 0.005）。COMT Val158Met无显著相关性（P = 0.156）。对照间多态性均处于Hardy-Weinberg平衡。结论：该研究提供了CYP3A4*1B和GSTP1 Ile105Val以及MTHFR C677T多态性与伊拉克人群乳腺癌易感性相关的法律证据，反映了这些特定的遗传风险，并加强了中东人群对乳腺癌治疗和干预策略的精准医学框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.