title: Association of myeloperoxidase polymorphism (G463A) with cervix cancer.
abstract: Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ(2). We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculty of Medicine, University of Lisbon, Avenida Prof. Egas Moniz, 1649-028, Lisbon, Portugal, cindy_castelao@hotmail.com.
authors.forename: Cindy
authors.initials: C
authors.lastname: Castelão
authors.forename: Alda Pereira
authors.initials: AP
authors.lastname: da Silva
authors.forename: Andreia
authors.initials: A
authors.lastname: Matos
authors.forename: Ângela
authors.initials: Â
authors.lastname: Inácio
authors.forename: Manuel
authors.initials: M
authors.lastname: Bicho
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bicho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase