The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

Ding, Peijian; Yang, Yang; Cheng, Luyang; Zhang, Xuejun; Cheng, Limin; Li, Caizhen; Cai, Jun

doi:10.1371/journal.pone.0092083

Cited by 23 publications

(18 citation statements)

References 27 publications

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“…It has been suggested that mutations in XRCC1, XRCC2 and XRCC3 genes may contribute to decreased or lost DNA repair capacity. Furthermore, SNP of XRCC1, XRCC2 and XRCC3 may affect the risk of several types of cancer, including thyroid carcinoma, glioma and breast cancer [21,28,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Yan¹,

Li²,

Li³

et al. 2016

Cell Physiol Biochem

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Background/Aims: DNA HRR pathway and BER pathway play vital roles in differentiated thyroid cancer (DTC) development, thus we supposed that polymorphisms of XRCC1, XRCC2, XRCC3 DNA repair genes are associated with thyroid cancer risk and progression. Methods: We searched the NCBI database for relevant literatures to determine eight SNPs to be included in our study (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539). Results: SNP of rs25487 was linked with a 53% decrease in DTC risk (OR: 0.47; 95%CI: 0.268-0.82; P = 0.01). For SNP of rs1799782, the homozygous TT genotype indicated a statistically significant 2-fold increased risk of DTC (OR: 2.09; 95%CI: 1.27-3.43; P < 0.001) after multivariate adjustment. For SNP of rs861539, the homozygous TT genotype suggested statistically significant 3-fold increased risk of DTC (OR: 3.02; 95%CI: 1.68-5.42; P < 0.001). No significant association between the other five SNPs and DTC risk. Besides that, female was linked with 47% increase in DTC risk (OR: 1.47; 95%CI: 1.062-2.04; P = 0.02) after multivariate adjustment. Similar results for most of the SNPs were obtained from subgroup analysis by different histological types of DTC. Haplotype analysis revealed that AGC and GGT haplotypes of XRCC1 polymorphisms were associated with DTC. Moreover, results from gene-gene interaction showed that XRCC1-rs25487, XRCC1- rs1799782 and XRCC3- rs861539 variants jointly contributed to a specifically increased risk of DTC, with the combination variant of rs1799782-CT heterozygote and rs861539-TT homozygote exhibiting a higher 3.66-fold risk of DTC (OR: 3.66; 95% CI: 1.476-9.091, P = 0.005). Conclusion: Polymorphisms of XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539), may play a critical role in DTC development and progression. Furthermore, XRCC1 variant can interact with XRCC3 variant to significantly increase DTC susceptibility. Identifying these genetic risk markers could provide evidence for exploring the insight pathogenesis and develop novel therapeutic strategies for DTC.

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Section: Discussionmentioning

confidence: 99%

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Yan¹,

Li²,

Li³

et al. 2016

Cell Physiol Biochem

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“…Taken together, there is significant evidence showing that these three genes are involve in modulating the pathway in the development of breast cancer. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) were inconclusively associated to breast cancer risk in case-control or meta-analysis studies in different populations (Wu et al, 2006;Bu et al, 2014;Dai et al, 2014;Ding et al, 2014;Feng et al, 2014;Guo et al, 2014;Qin et al, 2015), but association of these SNPs to breast cancer in Southeast Asia populations, especially in Malaysian women was unquestionably insufficient. Therefore, this pilot study investigates the association of these SNPs, together with etiology factors such as age and ethnicity, to breast cancer risk in Malaysian women.…”

Section: Introductionmentioning

confidence: 99%

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

Chong

Goh²,

See³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. Materials and Methods: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. Conclusions: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.Keywords: Breast cancer -CYP2E1 -Malaysian women -single nucleotide polymorphisms -STK15 -XRCC1

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“…XRCC2 has been explored and determined to play some roles in various types of human tumors, including breast cancer, thyroid cancer, pancreatic cancer and other types of carcinomas [30, 36-41]. Low levels of XRCC2 have been detected in breast cancer [42], whereas greater XRCC2 expression is present in rectal cancer and gastric cancer [30, 43]. It has been hypothesized that XRCC2 expression is related to the initiation or progression of carcinogenesis [44].…”

Section: Discussionmentioning

confidence: 99%

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer

Zhang¹,

An²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. Methods: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. Results: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke’s staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. Conclusion: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.

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The Relationship between Seven Common Polymorphisms from Five DNA Repair Genes and the Risk for Breast Cancer in Northern Chinese Women

Cited by 23 publications

References 27 publications

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer

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