Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily.
OBJECTIVE
Host factors, including genetic polymorphisms, may explain some of the individual differences in cervical cancer occurrence, and susceptibility information may be useful to address effective and specific preventive strategies for different countries. The purpose of the present study was to investigate the role of p53 codon 72, glutathione S-transferase class mu (GSTM1), glutathione S-transferase class theta (GSTT1), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms on the risk for infection and/or of cervical intraepithelial lesions in women attending a colposcopy service in Catania, Sicily, with an already reported high prevalence of human papillomavirus.


METHODS
To identify the association among individual genetic polymorphisms, human papillomavirus infection, and histological findings, a case-control study was designed. Furthermore, to assess the combined effects of these polymorphisms on cervical cancer risk, combined genotype frequencies were compared among case patients and controls.


RESULTS
Women homozygous for the p53 codon 72 Arg genotype were at a 5.6-fold higher risk for developing cervical intraepithelial neoplasia (CIN) 2 or 3 compared with those showing homozygosity for the Pro genotype or heterozygosity for the Pro/Arg genotype. The GSTM1 and GSTT1 null genotypes were overrepresented in infected patients and in women with CIN 2 or 3, although without any significant associations. A decreased risk for CIN of individuals homozygous for the MTHFR T allele was shown.


CONCLUSIONS
After multiple logistic analyses, the presence of the allele 677T of the MTHFR gene was the best explaining protective factor against cervical carcinogenesis, and the allelic distribution in the control group followed the Hardy-Weinberg equilibrium expectations. However, the findings of our study still remain to be confirmed by additional and larger population-based surveys.
Agodi
Antonella
A
Department of Biomedical Sciences, University of Catania, Catania, Italy, Via S. Sofia n. 87, 95123 Catania, Italy. agodia@unict.it
Barchitta
Martina
M
Cipresso
Rosalba
R
Marzagalli
Rubina
R
La Rosa
Nadia
N
Caruso
Melania
M
Castiglione
Maria Grazia
MG
Travali
Salvatore
S
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology; D015995:Prevalence; D012307:Risk Factors; D012802:Sicily / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
D005982:Glutathione Transferase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C413545:glutathione S-transferase T1