Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investig ated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1 B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modif ying the risk of smoking-related HNSCC, Allelisms of the CYP1A1, GSTT1, GST M1, and GSTT1 genes alone were not associated with an increased risk. CYP1B 1 codon 432 polymorphism was found to be a putative susceptibility factor i n smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significa ntly higher (P < 0.001) in the group of smoking cases when compared with sm oking controls, Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was di scovered when investigating smoking and nonsmoking cases for the susceptibl e genotype CYP1B1*2/*2, when compared with the presence of the genotype wil d type, In combination with polymorphic variants of the GST genes, a synerg istic-effect OR was observed. The calculated OR for the combined genotype C YP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7), The calculated OR for the c ombined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2 and 24 .1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors, The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is ref lected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 w ild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate sign ificantly to the individual susceptibility of smokers to HNSCC.