XPD, APE1, and MUTYH polymorphisms increase head and neck cancer risk: effect of gene-gene and gene-environment interactions

Abstract

In the present study, we investigated the effect of the DNA repair gene polymorphisms XPD Asp312Asn (G>A), APE1 Asp148Glu (T>G), and MUTYH Tyr165Cys (G>A) on the risk for head and neck cancer (HNC) in association with tobacco use in a population of Northeast India. The study subjects comprised of 80 HNC patients and 92 healthy controls. Genotyping was performed using amplification refractory mutation system-PCR (ARMS-PCR) for XPD Asp312Asn (G>A) and PCR using confronting two-pair primers (PCR-CTPP) for APE1 Asp148Glu (T>G) and MUTYH Tyr165Cys (G>A). The XPD Asp/Asn genotype increased the risk for HNC by 2-fold (odds ratio, OR = 2.072; 95 % CI, 1.025-4.190; p < 0.05). Interaction between APE1 Asp/Asp and XPD Asp/Asn as well as MUTYH Tyr/Tyr and XPD Asp/Asn genotypes further increased the risk by 2.9 (OR = 2.97; 95 % CI, 1.16-7.61; p < 0.05) and 2.3 (OR = 2.37; 95 % CI, 1.11-5.10; p< 0.05) folds, respectively. The risk was further increased in heavy smokers with the XPD Asp/Asn genotype and heavy tobacco chewers with XPD Asn/Asn genotype by 7.7-fold (OR = 7.749; 95 % CI, 2.53-23.70; p < 0.05) and 10-fold (OR = 10; 95 % CI, 1.26-79.13; p < 0.05), respectively. We thus conclude that the XPD Asp312Asn and APE1 Asp148Glu polymorphisms increase the risk for HNC in association with smoking and/or tobacco chewing in the population under study.

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms

“…The MUTYH protein acts as a BER glycosylase and is mainly involved in the repair of oxidative DNA lesions (34,40,46,49–56). MUTYH dysfunction may therefore be of special relevance in human tumourigenesis, since it is the only mechanism for repairing 8-oxo-dG/adenine mismatches (49).…”

“…Notably, this enzyme is a crucial component of the BER pathway due to its ability to process AP sites and other 3′DNA termini that may result, for example, from exposure to ionizing radiation or direct attack by free radicals (59,77,78). Among the 18 identified SNPs for the APEX1 gene, the most studied one is the T>G transition at codon 148 of exon 5, which leads to a change in amino acid from Asp to Glu (56). Its potential role on cancer was evaluated in four meta-analyses on breast cancer susceptibility (55,79–81), two meta-analyses on prostate cancer (82,83) and several studies on other types of cancer (84–87).…”

Effects of APE1 Asp148Glu polymorphisms on OPMD malignant transformation, and on susceptibility to and overall survival of oral cancer in Taiwan

“…A China study further reported that, although APE1 Asp148Glu polymorphisms did not correlate with oral cancer development, the combined effects of BER XRCC1 399Gln and APE1 148Gln polymorphisms might increase nasopharyngeal carcinoma risk . Similarly, an India study indicated that APE1 Asp148Glu polymorphisms were not associated with an increased risk of oral cancer, but the interaction between APE1 148Asp/Asp and XPD 312Asp/Asn polymorphisms could increase oral cancer risk . Genetic differences between different ethnicities and differences in the carcinogenesis or pathology of oral cancer development in different countries could partially explain the discrepant results of these oral cancer studies.…”

“…6 Similarly, an India study indicated that APE1 Asp148Glu polymorphisms were not associated with an increased risk of oral cancer, but the interaction between APE1 148Asp/Asp and XPD 312Asp/Asn polymorphisms could increase oral cancer risk. 34 Genetic differences between different ethnicities and differences in the carcinogenesis or pathology of oral cancer development in different countries could partially explain the discrepant results of these oral cancer studies. Further well-designed studies of larger populations and additional gene polymorphisms in the BER pathway are needed to verify these findings.…”

Identification of novel heterozygous Apex 1 gene variant (Glu87Gln) in patients with head and neck cancer of Indian origin

“…One major variant that is studied widely is Apex 1 Asp148Glu. The variant Asp148Glu of Apex 1 was studied widely among Caucasian and Asian population, and the allelic frequency of this variant (148Glu) is much higher in these population, 45.21% and 34.82%, respectively. The observations are obtained based on studies involving lung cancer, breast cancer, colorectal cancer, bladder cancer, prostate cancer, and gastric cancer, whereas only few studies were available on HNC.…”