Haplotype analysis of XRCC2 gene polymorphisms and association with increased risk of head and neck cancer

Abstract

We aimed to investigate the effect of hotspot variations of XRCC2 gene on the risk of head and neck cancer (HNC) in 400 patients and 400 controls. Five polymorphisms of XRCC2 gene G4234C (rs3218384), G4088T (rs3218373), G3063A (rs2040639), R188H (rs3218536) and rs7802034 were analyzed using Allele- specific polymerase chain reaction (ARMS-PCR) followed by sequence analysis. For rs3218373, the GG genotype indicated a statistically significant 3-fold increased risk of HNC (P < 0.001) after multivariate adjustment. For rs7802034, the GG genotype suggested statistically significant 2-fold increased risk of HNC (P < 0.001). For SNP of rs3218536, the AA genotype indicated a significant 3-fold increased risk of HNC (P < 0.001). Additionally, haplotype analysis revealed that TACAG, TGGAG, TACGG and TAGGA haplotypes of XRCC2 polymorphisms are associated with HNC risk. Two SNPs in XRCC2 (rs2040639 and rs3218384) were found increased in strong linkage disequilibrium. Furthermore, joint effect model showed 20 fold (OR = 19.89; 95% CI = 2.65–149.36, P = 0.003) increased HNC risk in patients carrying four homozygous risk alleles of selected polymorphisms. These results show that allele distributions and genotypes of XRCC2 SNPs are significantly associated with increased HNC risk and could be a genetic adjuster for the said disease.

Gene expression and prognosis of x-ray repair cross-complementing family members in non-small cell lung cancer

“…A variety of cancers have been associated with XRCC2 , such as breast [ 43 ], lung [ 44 ], pancreatic [ 45 ], and head and neck cancers [ 46 ]. Zienolddiny et al reported that there are associations between a set of genetic polymorphisms in DNA repair genes and the risk of lung cancer [ 44 ].…”

Evaluation of X-Ray Repair Cross-Complementing Family Members as Potential Biomarkers for Predicting Progression and Prognosis in Hepatocellular Carcinoma

“…XRCC2 had been shown to participate in chemoresistance to 5-Fluorouracil in colorectal cancer [35]. An increasing number of studies observed the relationship between the polymorphisms in the XRCC2 gene and the risk of multiple cancers [36,37]. However, recent research focused on the mechanisms that XRCC2 involved in the oncogenesis of cancer are not available yet.…”

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism

“…Three probands carrying the c.3124_3126delACCinsCAGCCAGGAACTG variant (rs786204542) in the ABCC8 gene and a total of 68,978 control samples were genotyped using the TWBv2 SNP array (Thermo Fisher Scientific, Inc., Santa Clara, CA, USA), a genome-wide SNP chip designed in 2017 for the Taiwanese Han population ( 18 ). After genotyping, SNPs fulfilling the following criteria were included for haplotype analysis: [1] SNPs located in the surrounding region (± 100 kb) of the ABCC8 gene; [2] with a minor allele frequency of >0.5% (excluding the rs786204542 variant); [3] a call rate >95%; and [4] satisfying the Hardy–Weinberg equilibrium (HWE) ( P > 0.0001) ( 19 ).…”

“…Two scales of chromosomal haplotype regions among the cases and controls generated from the genotyped data were tested: [1] the bilateral 50 Kb regions flanking rs786204542, and [2] the bilateral 20 SNPs [110.3 Kb upstream (rs117210015) and 62.8 Kb downstream (rs2237969)] flanking rs786204542. Haplotype frequencies were estimated using the SAS/Genetics HAPLOTYPE PROCEDURE (SAS Institute, Cary, NC, USA) and the stepwise expectation-maximization (EM) algorithm ( 19 , 20 ). The probability of individual’s particular haplotype was calculated given the haplotype frequency reached the maximum likelihood estimations (MLEs) by stepwise EM algorithm.…”