Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study
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ABSTRACT:
SUBMITTER: Yin H
PROVIDER: S-EPMC11230887 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundHepatoblastoma is a rare disease. Its etiology remains obscure. No epidemiological reports have assessed the relationship of High Mobility Group A2 (HMGA2) single nucleotide polymorphisms (SNPs) with hepatoblastoma risk. This case-control study leads as a pioneer to explore whether HMGA2 SNPs (rs6581658 A>G, rs8756 A>C, rs968697 T>C) could impact hepatoblastoma risk.MethodsWe acquired samples from 275 hepatoblastoma cases and 1018 controls who visited one of five independent hospitals located in the different regions of China. The genotyping of HMGA2 SNPs was implemented using the PCR-based TaqMan method, and the risk estimates were quantified by odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIn the main analysis, we identified that rs968697 T>C polymorphism was significantly related to hepatoblastoma risk in the additive model (adjusted OR=0.73, 95% CI=0.54-0.98, P=0.035). Notably, participants carrying 2-3 favorable genotypes had reduced hepatoblastoma risk (adjusted OR=0.71, 95% CI=0.52-0.96, P=0.028) in contrast to those carrying 0-1 favorable genotypes. Furthermore, stratification analysis revealed a significant correlation between rs968697 TC/CC and hepatoblastoma risk for males and clinical stage I+II. The existence of 2-3 protective genotypes was correlated with decreased hepatoblastoma susceptibility in children ≥17 months old, males, and clinical stage I+II cases, when compared to 0-1 protective genotype.ConclusionTo summarize, these results indicated that the HMGA2 gene SNPs exert a weak influence on hepatoblastoma susceptibility. Further validation of the current conclusion with a larger sample size covering multi-ethnic groups is warranted.
| S-EPMC7023882 | biostudies-literature
Project description:Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2, and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20-0.61, P=0.0002 and adjusted OR = 0.49, 95% CI = 0.30-0.81, P=0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02-2.92, P=0.043 and adjusted OR = 2.07, 95% CI = 1.07-4.01, P=0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30-4.44, P=0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.
| S-EPMC6013708 | biostudies-literature
Project description:Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.
| S-EPMC7150445 | biostudies-literature
Project description:Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorphisms in XP genes may be associated with a change in DNA repair capacity, which could be associated with colorectal cancer development. We assessed the association between 94 single nucleotide polymorphisms (SNPs) within seven XP genes (XPA-XPG) and the colorectal cancer risk in the Polish population. We genotyped 758 unselected patients with colorectal cancer and 1,841 healthy adults. We found that a significantly decreased risk of colorectal cancer was associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p < 0.0001) and the rs2228000_TT genotype (OR 0.29; p < 0.0001) compared to the reference genotype (CC). And an increased disease risk was associated with the XPD SNP, rs1799793_AG genotype (OR 1.44, p = 0.018) and rs1799793_AA genotype (OR 3.31, p < 0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD and XPG revealed haplotypes associated with an altered colorectal cancer risk. Stratified analysis by gender showed differences between the association of three SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males. Association analysis between age of disease onset and polymorphisms in XPD (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these variants in patients under and over 50 years of age. Our results confirmed that polymorphisms in XPC and XPD may be associated with the risk of colorectal cancer.
| S-EPMC4330403 | biostudies-literature
Project description:Hepatoblastoma (HB) is the most prevalent primary hepatic cancer in children aged 6 months to 3 years. LIN28A is recurrently mutated in various diseases, and critically involved in tumorigenesis. However, a limited number of studies have examined the involvement of LIN28A polymorphisms in HB risk. We used the TaqMan assay to genotype four LIN28A polymorphisms (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) in 275 Chinese children with HB and 1018 cancer-free controls from five medical centers in China. Their association with HB risk was evaluated on the basis of odds ratio (OR) and corresponding 95% confidence interval (CI). Overall, no significant associations were found in single locus and combine analysis. Interestingly, in the stratified analysis, we found that subjects with 1-3 risk genotypes were more likely to develop HB in patients ≥17 months of age (adjusted OR=1.76, 95% CI=1.04-2.98, P=0.034). The rs3811464 GA/AA genotypes were associated with decrease HB risk in patients with clinical stage III+IV disease (adjusted OR=0.50, 95% CI=0.26-0.96, P=0.038). Our results suggest that the LIN28A polymorphisms have a weak association with HB susceptibility in the Chinese children. LIN28A rs3811464 G>A may decrease HB risk in stage III+IV patients which need further validations with larger samples and different ethnicities.
| S-EPMC7847658 | biostudies-literature
Project description:Base excision repair (BER) acts upon the most important mechanism of the DNA repair system, protecting DNA stability and integrity from the mutagenic and cytotoxic effects. Multiple researches have indicated that single-nucleotide polymorphisms (SNPs) in the BER-related gene may be associated with the susceptibility of ovarian cancer. However, the results are controversial. In this two-center case-control study, 19 potentially functional SNPs in six BER-related genes (hOGG1, APE1, PARP1, FEN1, LIG3 and XRCC1) was genotyped in 196 ovarian cancer cases and 272 cancer-free controls. And, their associations with ovarian cancer risk were assessed by unconditional logistic regression analyses. We found that PARP1 rs8679 and hOGG1 rs293795 polymorphisms were associated with a decreased risk of ovarian cancer under dominant model (adjusted OR=0.39, 95% CI=0.17-0.90, P=0.026; and adjusted OR=0.36, 95% CI=0.13-0.99, P=0.049, respectively). Stratification analysis demonstrated that this association was more pronounced in the subgroups of lower BMI and patients with early menarche and serous carcinoma. Moreover, LIG3 rs4796030 AA/AC variant genotypes performed an increased risk of ovarian cancer under recessive model (adjusted OR=1.54, 95% CI=1.01-2.35, P=0.046), especially in the subgroups of higher BMI, early clinic stage and the carcinoma at the left. These results suggested that PARP1, hOGG1 and LIG3 polymorphisms might impact on the risk of ovarian cancer. However, more researches with larger and different ethnic populations are warranted to support our findings.
| S-EPMC7738827 | biostudies-literature
Project description:Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings.
| S-EPMC3660504 | biostudies-literature
Project description:Genetic variants of nucleotide excision repair (NER) genes have been extensively investigated for their roles in the development of prostate cancer (PCa); however, the published results have been inconsistent. In a hospital-based case-control study of 1,004 PCa cases and 1,055 cancer-free controls, we genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of NER genes (i.e., XPC, rs2228001 T>G and rs1870134 G>C; XPD, rs13181 T>G and rs238406 G>T; XPG, rs1047768 T>C, rs751402 C>T, and rs17655 G>C; and XPF, rs2276464 G>C) and assessed their associations with risk of PCa by using logistic regression analysis. Among these eight SNPs investigated, only XPC rs1870134 CG/CC variant genotypes were associated with a decreased risk of prostate cancer under a dominant genetic model (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] = 0.64-1.91, P = 0.003). Phenotype-genotype analysis also suggested that the XPC rs1870134 CG/CC variant genotypes were associated with significantly decreased expression levels of XPC mRNA in a mix population of different ethnicities. These findings suggested that XPC SNPs may contribute to risk of PCa in Eastern Chinese men.
| S-EPMC5421853 | biostudies-literature
Project description:Polymorphisms in nucleotide excision repair (NER) pathway genes are associated with the risk of breast cancer, but the relevance of these associations appeared to vary according to the ethnicity of the subjects. To systemically evaluate the potential associations between NER polymorphisms and breast cancer risk in a Chinese population, we carried out a case-control study on 450 breast cancer patients and 430 healthy controls. Sequenom MassARRAY was used for genotyping, and immunohistochemistry was performed to detect estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression in tumor tissue. Our results showed that ERCC1 rs11615 (additive model: ORadjusted: 1.36, 95% CI: 1.08-1.71, p = 0.009), XPC rs2228000 (additive model: ORadjusted: 1.39, 95% CI: 1.13-1.72, p = 0.002) and ERCC2/XPD rs50872 (additive model: ORadjusted: 1.32, 95% CI: 1.04-1.67, p = 0.021) were associated with an increased risk of breast cancer. Stratified analysis revealed three polymorphisms (rs11615, rs1800975, and rs50872) to be associated with breast cancer in menopausal females. Three polymorphisms were associated with specific breast cancer grades (rs11615 with grade 3, rs2228000 and rs50872 with grade 1-2). Two polymorphisms (rs2228001 and rs50872) were associated with the risk of breast cancer with negative lymph node involvement. rs1800975 and rs50872 were associated with the risk of ER- and PR- breast cancer, whereas rs11615 was associated with the risk of ER+ and PR+ breast cancer. We found that carriers of the T allele of ERCC1 rs11615, XPC rs2228000 and rs50872, particularly in postmenopausal females, have an increased risk of breast cancer.
| S-EPMC5356705 | biostudies-literature
Project description:Incidence of hepatoblastoma has been increasing, but the causes of this disease remain unclear. Some studies have suggested that abnormal expressions of ALKBH5 gene are associated with multiple cancers. This study aims to test the hypothesis that hepatoblastoma risk may be modulated by genetic polymorphisms in ALKBH5 gene based on genotyped data from samples of 328 cases and 1476 controls enrolled from eight hospitals in China. We used TaqMan assay to genotype ALKBH5 gene single nucleotide polymorphisms (SNPs) rs1378602G > A and rs8400G > A. We calculated the odds ratios (ORs) and P values using logistic regression models to estimate the association between hepatoblastoma risk and ALKBH5 gene SNPs. We found the rs1378602G > A and rs8400G > A could not impact hepatoblastoma risk in single or combined analysis. Stratified analysis revealed that subjects with the rs8400 AA genotype are prone to getting hepatoblastoma in the clinical stage III + IV subgroup (adjusted OR = 1.93, 95% CI = 1.20-3.10, P=0.007), when compared to those with GG/GA genotype. False-positive report probability validated the reliability of the significant results. Preliminary functional annotations revealed that rs8400 A is correlated with increased expression of ALKBH5 gene in the expression quantitative trait locus (eQTL) analysis. In all, our investigation presents evidence of a weak impact of ALKBH5 gene polymorphisms on hepatoblastoma risk, using the largest hepatoblastoma sample size. These findings shed some light on the genetic basis of hepatoblastoma, implicating the role of ALKBH5 gene polymorphisms in the etiology of hepatoblastoma.
| S-EPMC7997766 | biostudies-literature