Relationship between XPD, RAD51, and APEX1 DNA repair genotypes and prostate cancer risk in the male population of Rio de Janeiro, Brazil

Abstract

Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19–428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward

“…Titles and abstracts were screened for all papers produced by the literature search. Studies excluded from the primary analyses during title and abstract screening were reviews, [24][25][26] editorials, 27 animal or in vitro studies, 28 mechanistic studies (even if they used endpoints potentially related to clinical cancer, as epigenetic markers, telomere length, endocrine response), [29][30][31][32] papers on study protocols, 33 biostatistics methods papers, 34,35 epidemiological profiles and cohort descriptions, 36,37 risk/ exposure assessments 38 and other studies where human cancer was not a primary outcome. 39 The following search terms were used in PubMed to identify relevant journal articles assessing the relationship between human exposure to pesticides and cancer, which were published in 2017 or later:…”

The role of the APE1 Asp148Glu polymorphism on the risk of acute myeloid leukemia in Iraqi patients

“…According to Ana et al 35 the APE1 deficiency reduced the risk of developing prostate cancer, and this finding is explained by the simultaneous reduction of important DNA repair pathways. As a result, prostatic tissue is likely protected from the spread of potentially cancerous clones and prostatic cells have probably died.…”

BRCA2 3ʹ-UTR Polymorphism rs15869 Alters Susceptibility to Papillary Thyroid Carcinoma via Binding hsa-mir-1178-3p

“…Not surprisingly, numerous studies have identified polymorphisms located in genes of DSBR associated to the risk of a variety of benign and malignant tumors, for example, XRCC1 R399Q in breast cancer, 18 RAD51 135G/C in colorectal cancer, 19 XPD Lys751Gln in prostate cancer and so on. 20 The present study focuses on the effect of 3ʹ-UTR polymorphisms of DSBR genes on PTC risk based on a medium-sized case–control study.…”