Naqeeb Huma, Sehar Bismillah, Siraj Sami, Almajwal Ali Madi, Hajira Bibi, Faris MoezAlIslam, AlBlooshi Sharifa, Alsubaie Ali Saad R, Safdar Mahpara, Alam Iftikhar, Zeb Falak
Department of Human Nutrition and Dietetics, Women University Mardan, Mardan, Pakistan.
Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, United Kingdom.
Front Nutr. 2025 Jun 24;12:1548340. doi: 10.3389/fnut.2025.1548340. eCollection 2025.
BACKGROUND/OBJECTIVES: Fat mass and obesity associated (FTO) gene and anthropometric measurements might be associated with breast cancer (BC) risk. This study aimed to assess the interactions between single nucleotide polymorphism (SNP) rs9939609 of the FTO gene, anthropometric indices, and BC risk among pre- and post-menopause women with overweight/obesity in Pakistan.
This retrospective case-control study conducted on a convenience sample of 200 women divided into two groups: a case group comprised of 100 women diagnosed with BC, and control group comprised of 100 (age and menopausal status matched healthy women). Physical activity was assessed using validated questionnaire. Data on body mass index (BMI, kg/m2), waist-to-hip ratio (WHR, cm), sociodemographic, and blood samples were collected from both groups. The rs9939609 FTO gene polymorphism was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction and Sanger sequencing. Multiple regressions were presented as adjusted odds ratios (OR) and their respective confidence intervals (95% CI).
The FTO rs9939609 T > A polymorphism showed a significantly higher frequency of the homozygous AA genotype in BC patients compared to healthy controls (22% vs. 13%, < 0.05). The odds ratio for BC was 2.4 (CI = 1.09-5.3, < 0.05), indicating that women with the AA genotype were more susceptible to BC compared to those with the wild-type TT genotype. Additionally, BC patients exhibited significantly higher BMI (27 ± 4.0 vs. 25 ± 3.4, < 0.05) and WHR (0.88 ± 0.06 vs. 0.85 ± 0.08, < 0.05) compared to healthy controls. These findings suggest a significant association between the FTO rs9939609 AA genotype, obesity, and BC risk.
FTO gene polymorphism may be implicated in the etiopathogenesis of BC, both in FTO pre- and post-menopause women diagnosed with overweight/obesity. Future cohorts are required to confirm the association between the FTO gene and BC in obese women and to identify the underlying biological mechanisms.
背景/目的：脂肪量和肥胖相关（FTO）基因与人体测量指标可能与乳腺癌（BC）风险相关。本研究旨在评估巴基斯坦超重/肥胖的绝经前和绝经后女性中，FTO基因单核苷酸多态性（SNP）rs9939609、人体测量指标与BC风险之间的相互作用。
本回顾性病例对照研究采用便利抽样法，选取200名女性分为两组：病例组由100名被诊断为BC的女性组成，对照组由100名（年龄和绝经状态匹配的健康女性）组成。使用经过验证的问卷评估身体活动情况。收集两组的体重指数（BMI，kg/m²）、腰臀比（WHR，cm）、社会人口统计学数据和血液样本。采用四引物扩增阻滞突变系统聚合酶链反应和桑格测序对rs9939609 FTO基因多态性进行基因分型。多元回归以调整后的优势比（OR）及其各自的置信区间（95%CI）表示。
与健康对照组相比，BC患者中FTO rs9939609 T>A多态性的纯合子AA基因型频率显著更高（22%对13%，<0.05）。BC的优势比为2.4（CI=1.09-5.3，<0.05），表明与野生型TT基因型女性相比，AA基因型女性更易患BC。此外，与健康对照组相比，BC患者的BMI（27±4.0对25±3.4，<0.05）和WHR（0.88±0.06对0.85±0.08，<0.05）显著更高。这些发现表明FTO rs9939609 AA基因型、肥胖与BC风险之间存在显著关联。
FTO基因多态性可能参与了超重/肥胖的绝经前和绝经后FTO女性BC的发病机制。未来需要队列研究来证实肥胖女性中FTO基因与BC之间的关联，并确定潜在的生物学机制。
