The interplay between XPG‐Asp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysis

Abstract

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.

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies

“…There are many causes of the tumor, such as individual hereditary, chronic inflammation, unhealthy lifestyles, environmental pollution, and so on ( Bade and Dela Cruz, 2020 ; Dugué et al, 2022 ). Among them, the role of genetic inheritance was widely accepted ( Adolf et al, 2022 ). Numerous genome-wide association studies (GWAS), as well as case-control studies, have been performed in the last few decades to detect the association of thousands of genes and their mutation with cancer risk and prognosis ( Lin et al, 2021 ; Yang et al, 2021 ).…”