Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population

Henríquez-Hernández, Luis Alberto; Valenciano, A.; Arnalot, Palmira Foro; Álvarez-Cubero, M.J.; Cózar, J.M.; Suárez-Novo, José Francisco; Castells-Esteve, Manel; Fernández-Gonzalo, Pablo; De-Paula-Carranza, Belén; Ferrer, M.; Guedea, Ferrán; Pardo, G. Sancho; Craven-Bartle, Jordi; Ortiz-Gordillo, María José; Cabrera-Roldán, Patricia; Rodríguez-Melcón, J.I.; Herrera-Ramos, Estefanía; Rodríguez-Gallego, Carlos; Lara, Pedro C.

doi:10.1038/pcan.2015.63

Cited by 15 publications

(10 citation statements)

References 48 publications

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“…A number of polymorphisms have been identified in the XRCC6 promoter that correlate with increased carcinogenesis. The Ku70 C-61G polymorphism (SNP rs2267437) is associated with increased breast cancer incidence, RCC, HCC, prostate, and lung cancer [ 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]. The Ku70 promoter T-991C (SNP rs5751129) polymorphism is associated with HCC, gastric, oral, renal, and nasopharyngeal cancer susceptibility, and this novel polymorphism is predicted to lead to differential XRCC6 mRNA and Ku70 protein expression levels [ 115 , 120 , 121 , 122 , 123 ].…”

Section: Core Nhej Factors In Carcinogenesis and Cancermentioning

confidence: 99%

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Sishc

Davis

2017

Cancers

135

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DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

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Section: Core Nhej Factors In Carcinogenesis and Cancermentioning

confidence: 99%

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Sishc

Davis

2017

Cancers

135

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“…X‐ray repair cross‐complementing 5 ( XRCC5 ) and 6 ( XRCC6 ) are key genes of the non‐homologous end joining (NHEJ) repair pathway, which is an important DNA repair mechanism. XRCC5 / 6 polymorphisms correlate with susceptibility to develop various malignant tumors 7,8 . XRCC5 rs16855458 and rs9288516 have potential biological functions as they cause changes in the binding sites of transcription factors, and correlate with risk for hepatocellular carcinoma, 9,10 whereas XRCC6 rs2267437 and XRCC5 rs3835 were correlated with breast cancer risk in European women 11 .…”

Section: Introductionmentioning

confidence: 99%

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi‐center study

et al. 2021

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Background X‐ray repair cross‐complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene‐environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. Methods The study included 1039 patients with breast cancer and 1040 controls. Four single‐nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene‐environment interactions were analyzed using logistic regression with multiplicative interaction models. Results XRCC5 rs16855458 was associated with increased breast cancer risk in the co‐dominant (ptrend = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07–1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor‐negative/progesterone receptor‐negative (ER−/PR−) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12–2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction = 0.0497). However, these interactions became insignificant after Bonferroni correction. Conclusion XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER−/PR− breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

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“…Information about their effect on the various markers of the CBMN cyt assay would be most valuable, since the elevated levels of these endpoints in peripheral lymphocytes might indicate an increased cancer risk. As this association may sometimes be observed regardless of known high exposure to carcinogens, individual susceptibility factors, such as DNA repair polymorphisms may play an important role (Bonassi et al, ; Langsenlehner et al, ; Mirecka et al, ; Henriquez‐Hernandez et al, ). Many polymorphisms have been associated with an increased risk of cancer and might be expected to be associated with a higher level of chromosome damage (Norppa, ; Dhillon et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cytokinesis Block Micronucleus Cytome (CBMN Cyt) Assay Biomarkers and Their Association With Radiation Sensitivity Phenotype in Prostate Cancer Cases and DNA Repair Gene hOGG1 (C1245G) Polymorphism

Dhillon

Yeoh

Salisbury

et al. 2018

Environ and Mol Mutagen

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Prostate cancer (PC) is commonly diagnosed cancer in men but only a few risk factors, such as family history, ethnicity, and age have been established. Chromosomal instability is another possible risk factor but this has not been adequately explained previously. In this study, we tested the hypotheses that peripheral blood lymphocytes (PBL) of PC patients have (1) an abnormally high level of chromosomal instability; (2) that they are hypersensitive to ionizing radiation‐induced DNA damage; and (3) that these phenotypes are affected by hOGG1 (C1245G) polymorphism. These experiments were performed using the cytokinesis‐block micronucleus Cytome (CBMN cyt) assay in PC cases and controls. We found that spontaneous or radiation‐induced (3G) micronucleus (MN) frequency is not significantly different between both groups. However, spontaneous frequency of nucleoplasmic bridges (NPBs) and radiation‐induced nuclear buds (NBuds) were significantly higher in patients vs. controls (P < 0.0001; P = 0.0005, respectively). In addition, apoptosis and nuclear division index (NDI) was significantly higher in patients compared to controls after radiation treatment (P = 0.006; P = 0.0002, respectively). Furthermore carriage of at least one G allele of hOGG1 (C1245G) polymorphism was associated with a significantly increased odds ratio (OR) to have a base‐line MN, NPB, or NBud frequency greater than medium level compared to homozygotes for C allele (OR:1.94, 1.77, 2.36, respectively, P = 0.02; 0.04, and 0.004, respectively). Our results support the hypotheses that those who develop PC have significantly higher level of genomic instability which is further increased in those who carry G allele of the hOGG1 (C1245G) polymorphism. Environ. Mol. Mutagen. 59:813–821, 2018. © 2018 Wiley Periodicals, Inc.

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Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population

Abstract: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Cited by 15 publications

References 48 publications

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi‐center study

Cytokinesis Block Micronucleus Cytome (CBMN Cyt) Assay Biomarkers and Their Association With Radiation Sensitivity Phenotype in Prostate Cancer Cases and DNA Repair Gene hOGG1 (C1245G) Polymorphism

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