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

dc.contributor.authorRweyemamu, Linus Paul
dc.contributor.authorAdolf, Ismael C
dc.contributor.authorAkan, Gokce
dc.contributor.authorMselle, Ted F
dc.contributor.authorDharsee, Nazma
dc.contributor.authorNamkinga, Lucy
dc.contributor.authorLyantagaye, Sylvester L
dc.contributor.authorAtalar, Fatmahan
dc.date.accessioned2022-11-24T13:06:10Z
dc.date.available2022-11-24T13:06:10Z
dc.date.issued2022-06-12
dc.descriptionNILen_US
dc.description.abstractBackground 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.en_US
dc.description.sponsorshipN/Aen_US
dc.identifier.citationAdolf AC, Rweyemamu LP, Akan G, Mselle TF, Dharsee N, Namkinga LA, Lyantagaye SL, Atalar F. The interplay between XPG-Asp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysis.Cancer Medicine 2022;00:1-16. DOI: https://doi.org/10.1002/cam4.4914en_US
dc.identifier.doihttps://doi.org/10.1002/cam4.4914
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5910
dc.language.isoen_USen_US
dc.publisherWILEYen_US
dc.relation.ispartofseries2022;cam4.4914
dc.subjectbreast cancer, DNA repair genes, multifactor dimensionality reduction, polymorphism, XPGen_US
dc.titleThe interplay between XPG-Asp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysisen_US
dc.typeJournal Article, Peer Revieweden_US
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