Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1 - Relation to the incidence rate of cervical carcinoma

BACKGROUND, The authors established the genotype frequencies of cytochrome P450 (CYP1A1/MspI, CYP2E1/PstI, and CYP2E1/DraI), glutathione-S-transferase (GSTM1 and GSTT1), and p53 (exon 4/AccII and intron 3/16-base pair duplica tion) gene polymorphisms in cervical carcinoma patients and controls and ev aluated the association between the specific genotype or genotype combinati ons of these polymorphisms and the risk of cervical carcinoma. METHODS. In this case-control study, the genotypes of 181 human papillomavi rus (HPV)-16 or HPV-18 positive cervical carcinoma patients and 1-to-1 age- matched controls were determined using a polymerase chain reaction-based te chnique. RESULTS. Among these polymorphisms, the individuals carrying arginine/proli ne genotypes of p53 showed a 9.5-fold increase of cervical carcinoma risk ( 95% confidence interval [CI], 4.9-18.6) compared with those individuals car rying arginine/arginine genotypes. The frequency of overall GSTT1 null geno types also was significantly higher in cervical carcinoma patients compared with that of GSTT1 positive genotypes (P = 0.003; odds ratio [OR] = 1.9; 9 5% CI, 1.2-2.9). The genotype combination of p53 and GST played a more impo rtant role in describing the relative risk of cervical carcinoma. The indiv iduals carrying both the arginine/ proline genotype of p53 and the null gen otype of GSTT1 showed a 3.5-fold increase of cervical carcinoma risk [95% C I, 1.8-7.1] compared with those individuals carrying both the arginine/argi nine genotype of p53 and the GSTT1 positive genotype. In the patients who w ere stratified into the two age groups, the null genotypes of GSTT1 (69.1% vs. 45.5%; P = 0.016) and GSTM1 (61.8% vs. 40.0%; P = 0.028) in cervical ca rcinoma were significantly overrepresented in the younger age subgroup (age 40 years or younger) compared with those of controls. Especially in this a ge group, the individuals carrying both null genotypes of GSTT1 and GSTM1 s howed a 17.8-fold increase of cervical carcinoma risk (95% CI, 2.2-141.0) c ompared with the individuals carrying both positive genotypes of GSTT1 and GSTM1. CONCLUSIONS. The results of the current study suggested that the arginine/p roline genotype of p53, independently or in conjunction with the GSTT1 null genotype, could affect the genetic susceptibility for cervical carcinoma, and HPV positive women carrying both null genotypes of GSTT1 and GSTM1 have an increased risk of cervical carcinoma developing before age 40 years. (C ) 2000 American Cancer Society.