ORIGINAL ARTICLE Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors Rumaisa Rafiq 1 & Gulzar Ahmad Bhat 1 & Mohd Maqbool Lone 2 & Akbar Masood 1 & Nazir Ahmad Dar 1 Received: 9 September 2015 /Accepted: 20 January 2016 # International Society of Oncology and BioMarkers (ISOBM) 2016 Abstract The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A ( XPA ) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental fac- tors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR)= 3.57; 95 % confidence inter- val (CI) = 1.76–7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01–8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74–18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30–16.69), or had a posi- tive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67–19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR=4.43; 95 % CI = 2.41–8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in com- bination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14–15.64) and such association was synergisti- cally significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures. Keywords Xeroderma pigmentosum A and C . Polymorphism . Gene-environment interaction . Esophageal squamous cell carcinoma risk . Kashmir Introduction DNA repair genes maintain the integrity and the stability of a human genome by unceasingly repairing the DNA damage caused by metabolic activities or environmental exposures [1, 2]. Different pathways correct different types of genome damages. One such versatile damage-correcting machinery is nucleotide excision repair (NER) [3, 4] which involves recog- nition, followed by confirmation and, finally, repair of the DNA damage [ 5]. The NER is initiated by xeroderma pigmentosum A ( XPA) and xeroderma pigmentosum C (XPC) gene products particularly in correcting the bulky DNA adducts or thymidine dimers [5–7]. The activities of the XPA and XPC are not same among the individuals of a population [8]. If the ability to sense the dam- age is ceased, the chances of damage retention increase which Electronic supplementary material The online version of this article (doi:10.1007/s13277-016-4895-3) contains supplementary material, which is available to authorized users. * Nazir Ahmad Dar nazirramzan@uok.edu.in 1 Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India 190006 2 Department of Radiation Oncology, SK Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India 190011 Tumor Biol. DOI 10.1007/s13277-016-4895-3