Fas/CD95 promoter polymorphism gene and its relationship with cervical carcinoma.
OBJECTIVE
Apoptosis is an important fail-safe control in human papillomavirus (HPV)-associated carcinogenesis. We tested the hypothesis that the A/G polymorphism at -670 of Fas promoter is associated with an increased risk for cervical cancer, using a matched case-control setting.


METHODS
The material in this case-control study consisted of 91 patients with cervical carcinoma and 176 population-based control subjects, recruited between 2002 and 2004; all the ethnic Brazilian women had histologically confirmed cervical carcinoma. Control subjects were age-matched; healthy women who were selected following a negative cervical cytology and normal colposcopy. Fas genotyping was performed using a PCR-RFLP technique.


RESULTS
No significant difference existed in the distribution of the Fas polymorphisms (wild, heterozygous, mutant) between the cases and controls. The heterozygous (OR: 4.85, 95% CI: 1.1-22.6) genotypes among the younger (< 48 yrs) cancer patients were almost 5-fold increased, as compared with the wild type. No such increase was observed among the patients older than 48 years.


CONCLUSIONS
Our data suggest that 670A/G polymorphism in the promoter region of the death receptor Fas is associated with an increased risk of cervical cancer among Brazilian women under 48 years. The mechanisms would be the inhibition of apoptosis by Fas -670G allele-mediated down-regulation of Fas transcription.
Zucchi
F
F
Department of Gynecology, Federal University of São Paulo, Paulista School of Medicina, São Paulo, Brazil. flaviozucchi@ig.com.br
da Silva
I D C G
ID
Ribalta
J C L
JC
de Souza
N C N
NC
Speck
N M de Góis
NM
Girão
M J B C
MJ
Brenna
S M F
SM
Syrjänen
K J
KJ
D000328:Adult; D017209:Apoptosis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053218:Receptors, Death Domain / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
C491901:FAS protein, human; D053218:Receptors, Death Domain; D019014:fas Receptor