Elucidation of Increased Cervical Cancer Risk Due to Polymorphisms in XRCC1 (R399Q and R194W), ERCC5 (D1104H), and NQO1 (P187S)

Das, Agneesh Pratim; Saini, Sandeep; Tyagi, Shrishty; Chaudhary, Nisha; Agarwal, Subhash Mohan

doi:10.1007/s43032-022-01096-6

Cited by 2 publications

(3 citation statements)

References 66 publications

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“…In the Chilean population, NQO1 rs1800566 shows a higher prevalence compared to Admixed American, European, and African populations ( Figure 2 ), resembling patterns observed in East Asians. Although not significantly associated with overall cancer risk, stratified genotyping studies have linked this SNP to reduced incidences of hepatocellular carcinoma, renal cell carcinoma, stomach cancer in one study [ 52 ], and cervical cancer in another [ 53 ]. In the DNA damage repair gene XRCC1 , the allelic frequency of the SNP rs25487 is reduced in the Chilean population compared to the Admixed American population ( Figure 2 ), and this SNP has previously been associated with an increased risk of cervical cancer [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although not significantly associated with overall cancer risk, stratified genotyping studies have linked this SNP to reduced incidences of hepatocellular carcinoma, renal cell carcinoma, stomach cancer in one study [ 52 ], and cervical cancer in another [ 53 ]. In the DNA damage repair gene XRCC1 , the allelic frequency of the SNP rs25487 is reduced in the Chilean population compared to the Admixed American population ( Figure 2 ), and this SNP has previously been associated with an increased risk of cervical cancer [ 53 ]. These findings underscore the intricate interplay between genetic variations, drug response, and cancer susceptibility, necessitating a comprehensive understanding of personalized therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

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Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population

Owen,

Cordova-Delgado,

Bustos

et al. 2024

Pharmaceutics

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Background: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry. Methods: To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with p ≤ 0.05 and Bonferroni’s multiple adjustment tests determined statistical differences between allele frequencies. Results: Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase (DPYD) variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 (NUDT15) rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of TMPT gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031–0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene (UGT1A1) rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations. Conclusions: This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population

Owen,

Cordova-Delgado,

Bustos

et al. 2024

Pharmaceutics

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“…These genes are associated with the DNA double-stranded break repair process (DSB), base excision repair pathway (BER), DNA mismatch repair process (MMR), and nucleotide excision repair pathways (NER), respectively. As the functions of these genes involve DNA repair and maintenance of genome stability and integrity, any perturbation of these gene products may be lethal for various cellular processes [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk

Das

Chaudhary

Tyagi

et al. 2023

Genes

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Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI). Cochran’s Q-test and I2 were used to study heterogeneity, based on which either a random or a fixed effect model was implemented. The meta-analysis identified 11 SNPs (from 10 genes) to be significantly associated with increased EC risk. Among these, seven SNPs were significant in at least three of the five genetic models, as well as three of the polymorphisms (rs1801320, rs11224561, and rs2279744) corresponding to RAD51, PGR, and MDM2 genes, which contained more than 1000 EC cases each and exhibited increased risk. The current meta-analysis indicates that polymorphisms associated with various hormone related genes—SULT1A1 (rs1042028), PGR (rs11224561), and CYP19A1 (rs10046 and rs4775936); DNA repair genes—ERCC2 (rs1799793), OGG1 (rs1052133), MLH1 (rs1800734), and RAD51 (rs1801320) as well as genes like MDM2 (rs2279744), CCND1 (rs9344), and SERPINE1 (rs1799889), are significantly associated with increased EC risk.

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Elucidation of Increased Cervical Cancer Risk Due to Polymorphisms in XRCC1 (R399Q and R194W), ERCC5 (D1104H), and NQO1 (P187S)

Cited by 2 publications

References 66 publications

Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population

Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk

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