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XPG Asp1104His polymorphism increases colorectal cancer risk especially in Asians.

ABSTRACT: Xeroderma pigmentosum group G (XPG) protein is a pivotal element of the nucleotide excision repair pathway. XPG gene single nucleotide polymorphisms (SNPs) have been shown to confer colorectal cancer (CRC) susceptibility. In this study, we further investigated the role of Asp1104His (rs17655 G > C) in XPG on CRC risk. We genotyped the rs17655 G > C polymorphism in Chinese population comprising 1019 CRC cases and 1036 cancer-free controls. We also performed a meta-analysis to further assess the association. Overall, no significant association was detected between the rs17655 G > C and the risk of CRC. Stratified analysis also revealed no significant association. To further elucidate the association of the rs17655 with CRC susceptibility, we conducted a meta-analysis by including qualified publications and the current study. The meta-analysis results demonstrated that rs17655 G > C was associated with an increased CRC risk (CG vs. GG: OR = 1.14, 95% CI = 1.01-1.28; CC/CG vs. GG: OR = 1.12, 95% CI = 1.01-1.24; C vs. G: OR = 1.06, 95% CI = 1.01-1.11). In subgroup analysis, the significant association between the rs17655 C allele and CRC risk was found in Asians and hospital-based subgroups. Taken together, our results suggested that the XPG rs17655 G > C polymorphism is a low-penetrance susceptibility locus for CRC. Further studies are warranted to validate these findings.

SUBMITTER: Su J

PROVIDER: S-EPMC6413257 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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XPG Asp1104His polymorphism increases colorectal cancer risk especially in Asians.

Su Jinsong J Zhu Ying Y Dai Baiyun B Yuan Weitang W Song Junmin J

American journal of translational research 20190215 2

Xeroderma pigmentosum group G (XPG) protein is a pivotal element of the nucleotide excision repair pathway. XPG gene single nucleotide polymorphisms (SNPs) have been shown to confer colorectal cancer (CRC) susceptibility. In this study, we further investigated the role of Asp1104His (rs17655 G > C) in XPG on CRC risk. We genotyped the rs17655 G > C polymorphism in Chinese population comprising 1019 CRC cases and 1036 cancer-free controls. We also performed a meta-analysis to furthe ...[more]

PMID: 30899401

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Project description:BackgroundReproductive 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.ResultsThe 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.ConclusionsThe XPG-Asp1104His (rs17655) might exert both independent and interactive effects on BC development in the Tanzanian women.

Dataset Information

XPG Asp1104His polymorphism increases colorectal cancer risk especially in Asians.

Publications

<i>XPG</i> Asp1104His polymorphism increases colorectal cancer risk especially in Asians.

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