Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia.
Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of cervical cancer (CC). However, most infected women do not develop cancer. Therefore, exposure to other carcinogenic agents may be a contributing risk factor for CC. We investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (CYP2E1, GSTM1, and mEH) significantly increase the risk for neoplasia. We selected 76 cases with high-grade cervical neoplasia or with invasive CC and 75 matched healthy controls. The collected data support the well-established observation that infection with high-risk HPV is the major risk factor for CC (OR = 75; 95% CI = 26-220). In addition, our data show that women who smoked more than 15 "pack-year" had a significant 6.9-fold increase in risk (95% CI = 1.2-40.3) after adjustment for HPV infection. The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. A significant increase in risk for neoplasia was observed for the low-activity mEH 113 His allele after adjustment for smoking (OR = 3.0; 95% CI = 1.4-6.3). The GSTM1 null genotype was associated with a significant 3.3-fold increased risk for neoplasia (95% CI = 1.0-11.8) compared to women who were GSTM1-positive after adjustment for smoking and HPV infection. Our study suggests that genetic differences in the metabolism of cigarette smoke, particularly GSTM1, may confer susceptibility to CC. Further studies using larger populations will be needed to confirm our observations and to validate data for disease prevention.
Sierra-Torres
Carlos H
CH
Department of Preventive Medicine and Community Health, 700 Harborside Drive, University of Texas Medical Branch, Galveston, TX 77555, USA.
Au
William W
WW
Arrastia
Concepcion D
CD
Cajas-Salazar
Nohelia
N
Robazetti
Sonia C
SC
Payne
Deborah A
DA
Tyring
Stephen K
SK
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014412:Tumor Virus Infections / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
D019392:Cytochrome P-450 CYP2E1; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase