Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia

Authors

  • Carlos H. Sierra-Torres,

    1. Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
    2. Laboratorio de Genética Humana, Departamento de Ciencias Fisiológicas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia
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  • William W. Au,

    Corresponding author
    1. Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
    • Department of Preventive Medicine and Community Health, 700 Harborside Drive, University of Texas Medical Branch, Galveston, TX 77555
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  • Concepcion D. Arrastia,

    1. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
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  • Nohelia Cajas-Salazar,

    1. Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
    2. Unidad de Toxicología Genética y Citogenética, Departamento de Biología, Facultad de Ciencias Naturales, Exactas y de la Educación, Universidad del Cauca, Popayán, Colombia
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  • Sonia C. Robazetti,

    1. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
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  • Deborah A. Payne,

    1. Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas
    2. Department of Pathology, University of Texas Medical Branch, Galveston, Texas
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  • Stephen K. Tyring

    1. Department of Dermatology, University of Texas Medical Branch, Galveston, Texas
    2. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
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Abstract

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. Environ. Mol. Mutagen. 41:69–76, 2003. © 2003 Wiley-Liss, Inc.

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