Polymorphisms in CYP2A13 and UGT1A7 genes and head and neck cancer susceptibility in North Indians.
OBJECTIVE
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).


CONCLUSIONS
Interplay between genetic variants of CYP2A13 and UGT1A7 genes and smoking may modulate susceptibility to head and neck cancer.
Department of Otolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
R
R
Sharma
M
M
Ahuja
Nk
N
Panda
M
M
Khullar
D000428:Alcohol Drinking / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D003596:Cytosine; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D013941:Thymine; D014026:Nicotiana
D002273:Carcinogens; D003062:Codon; D003596:Cytosine; D001189:Aryl Hydrocarbon Hydroxylases; C414206:CYP2A13 protein, human; D014453:Glucuronosyltransferase; C524630:UGT1A7 protein, human; D013941:Thymine