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Polymorphisms in CYP2A13 and UGT1A7 genes and head and neck cancer susceptibility in North Indians
Author(s) -
Sharma R,
Ahuja M,
Panda NK,
Khullar M
Publication year - 2010
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/j.1601-0825.2010.01683.x
Subject(s) - head and neck cancer , allele , genotype , haplotype , gene , cancer , genetics , polymerase chain reaction , biology , denaturing high performance liquid chromatography , genetic predisposition , medicine
Oral Diseases (2010) 16 , 760–768 Objectives: To examine role of genetic variants of CYP2A13 and UGT1A7 genes, involved in activation and detoxification of tobacco carcinogens, with risk of head and neck cancer as well as to assess the potential modifying role of gene‐gene and gene‐environment interactions. Methods: 203 head and neck cancer patients and 201 healthy controls were genotyped for functional polymorphisms of CYP2A13 and UGT1A7 genes using polymerase chain reaction‐restriction fragment length polymorphism, denaturing high‐performance liquid chromatography and sequencing. Results: We identified two novel polymorphisms T478C and T494C in CYP2A13 gene which were associated with significantly reduced risk of cancer (OR 0.37; 95% CI 0.19–0.71; P < 0.05). A CYP2A13 haplotype carrying variant alleles of T478C/T494C was found to be associated with reduced risk of head and neck cancer (OR 0.42; 95% CI 0.22–0.78; P = 0. 005). Mutant ‘T’ allele of CYP2A13 C578T polymorphism was found to be present in cancer patients only. A sevenfold increased risk of cancer was observed in smokers with UGT1A7 low activity genotypes (OR 7.01; 95% CI 1.02–48.37; P < 0.05). UGT1A7 haplotype carrying C allele (T622C) showed 10‐fold increased risk of cancer (OR 10.12; 95% CI 1.29–79.4; P < 0.05). Conclusion: Interplay between genetic variants of CYP2A13 and UGT1A7 genes and smoking may modulate susceptibility to head and neck cancer.