XPG-Asp1104His 多态性与生殖危险因素之间的相互作用增加了坦桑尼亚妇女患乳腺癌的风险：一项多重交互作用分析。
The interplay between XPG-Asp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysis.
机构信息
University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania.
University of Dar es Salaam, Department of Molecular Biology and Biotechnology, Dar es Salaam, Tanzania.
出版信息
Cancer Med. 2023 Jan;12(1):472-487. doi: 10.1002/cam4.4914. Epub 2022 Jun 12.
BACKGROUND
Reproductive history and genetics are well-known risk factors of breast cancer (BC). Little is known about how these factors interact to effect BC. This study investigated the association of ten polymorphisms in DNA repair genes with BC susceptibility in the Tanzanian samples and further analyzed the association between reproductive risk factors and disease risk METHODS: A hospital-based case-control study in 263 histopathological confirmed BC patients and 250 age-matched cancer-free controls was carried out. Allelic, genotypic, and haplotype association analyses were executed. Also, multifactor dimensionality reduction (MDR), and interaction dendrogram approaches were performed.
RESULTS
The frequency of genotypic and allelic variants of XRCC1-Arg399Gln (rs25487), XRCC2-Arg188His (rs3218536), XRCC3-Thr241Met (rs861539), XPG-Asp1104His (rs17655), and MSH2-Gly322Asp (rs4987188) were significantly different between the groups (p < 0.05). Moreover, XRCC1-Arg399Gln (rs25487), XRCC3-Thr241Met (rs861539), and XPG-Asp1104His (rs17655) were associated with the increased risk of BC in co-dominant, dominant, recessive, and additive genetic-inheritance models (p < 0.05). XRCC1-Arg/Gln genotype indicated a 3.1-fold increased risk of BC in pre-menopausal patients (p = 0.001) while XPG-His/His genotype showed a 1.2-fold increased risk in younger BC patients (<40 years) (p = 0.028). Asp/His+His/His genotypes indicated a 1.3-fold increased risk of BC in PR+ patients and a 1.1-fold decreased risk of BC in luminal-A patients (p = 0.014, p = 0.020, respectively). MDR analysis revealed a positive interaction between BC and the XPG-Asp1104His (rs17655) together with family history of cancer in the first-degree relatives. Dendrogram analysis indicated that the XPG-Asp1104His (rs17655) and family history of cancer in first-degree relatives were significantly synergistic and might be associated with an elevated risk of BC in Tanzania.
CONCLUSIONS
The XPG-Asp1104His (rs17655) might exert both independent and interactive effects on BC development in the Tanzanian women.
背景
生殖史和遗传学是乳腺癌（BC）的已知危险因素。目前对于这些因素如何相互作用影响 BC 知之甚少。本研究在坦桑尼亚样本中调查了 10 个 DNA 修复基因中的多态性与 BC 易感性的关系，并进一步分析了生殖危险因素与疾病风险之间的关系。
方法
在 263 例经组织病理学证实的 BC 患者和 250 例年龄匹配的无癌症对照中进行了一项基于医院的病例对照研究。进行了等位基因、基因型和单倍型关联分析。还进行了多因素维度缩减（MDR）和相互作用树状图方法。
结果
XRCC1-Arg399Gln(rs25487)、XRCC2-Arg188His(rs3218536)、XRCC3-Thr241Met(rs861539)、XPG-Asp1104His(rs17655)和 MSH2-Gly322Asp(rs4987188)的基因型和等位基因变异频率在组间存在显著差异（p<0.05）。此外，XRCC1-Arg399Gln(rs25487)、XRCC3-Thr241Met(rs861539)和 XPG-Asp1104His(rs17655)在共显性、显性、隐性和加性遗传模型中与 BC 风险增加相关（p<0.05）。XRCC1-Arg/Gln 基因型在绝经前患者中提示 BC 风险增加 3.1 倍（p=0.001），而 XPG-His/His 基因型在年轻 BC 患者（<40 岁）中提示 BC 风险增加 1.2 倍（p=0.028）。Asp/His+His/His 基因型在 PR+患者中提示 BC 风险增加 1.3 倍，在 luminal-A 患者中提示 BC 风险降低 1.1 倍（p=0.014，p=0.020）。MDR 分析显示，BC 与 XPG-Asp1104His(rs17655)之间存在阳性相互作用，与一级亲属的癌症家族史有关。树状图分析表明，XPG-Asp1104His(rs17655)和一级亲属的癌症家族史具有显著的协同作用，可能与坦桑尼亚妇女的 BC 风险升高有关。
结论
XPG-Asp1104His(rs17655)可能对坦桑尼亚妇女的 BC 发展产生独立和交互作用。
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