Cervical cancer and CYP2E1 polymorphisms: implications for molecular epidemiology.
BACKGROUND
Besides human papillomavirus (HPV) infection, several cofactors are considered important for the development of cervical cancer (CC). Among these, tobacco smoke, other sexually transmitted diseases, inflammation and nutritional factors have been intensively described. CYP2E1 polymorphisms have been associated with the metabolization of several carcinogens, some of them considered risk factors for CC development, such as tobacco smoke. The aim of this study was to evaluate the role of CYP2E1 polymorphisms in the susceptibility to cervical cancer in a Portuguese population.


METHODS
The genotypic analysis was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, using peripheral blood samples of 454 individuals: 122 presented invasive squamous cell carcinoma (ICC), 59 presented squamous intraepithelial lesions (SIL), and the control population was composed of 274 healthy individuals.


RESULTS
Concerning the DraI polymorphism, we observed a decreased risk for the development of squamous cervical lesions in the presence of the C allele [odds ratio (OR)=0.600; 0.378<OR<0.952; p=0.029]. In the stratification of the analysis according to the mean age, we observed an increased risk for the development of SIL, for women older than 39 years of age, in the presence of the D allele (OR=0.087; 0.012<OR<0.651; p=0.003). Regarding the RsaI polymorphism, we did not find any significant differences.


CONCLUSIONS
The decreased risk observed for the development of SIL and not ICC in the presence of the D allele may indicate that CYP2E1 interferes with the initial steps of the carcinogenic process, probably due to its involvement in the action of immunological mediators, expressed during cervical inflammation. These aspects may help to define new therapeutic strategies for chemoprevention.
Ferreira
Paula M
PM
Oncologia Molecular-Laboratórios, Instituto Português de Oncologia-Porto, Piso 4, Rua Dr António Bernardino de Almeida, 4200-072, Porto, Portugal.
Catarino
Raquel
R
Pereira
Deolinda
D
Matos
Ana
A
Pinto
Daniela
D
Coelho
Ana
A
Lopes
Carlos
C
Medeiros
Rui
R
D000328:Adult; D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011174:Portugal / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000235:genetics
D019392:Cytochrome P-450 CYP2E1