Role of glutathione-S-transferase and codon 72 of P53 genotypes in epithelial ovarian cancer patients.
OBJECTIVE
A series of polymorphisms in germ-line DNA have been investigated in an effort to delineate polygenic models of cancer susceptibility and prognosis. As low-penetrance susceptibility genes may combine additively or multiplicatively and contribute to cancer incidence and to the response to chemotherapy, we studied GSTT1, GSTM1, GSTO2, GSTP1 and codon 72 of p53 genotype profiles in ovarian cancer patients.


METHODS
We compared 69 ovarian cancer patients with 222 control healthy women paired for ethnic and life-style characteristics. Outcome was evaluated in 29 stage III and IV patients submitted to a platinum-based chemotherapy followed-up for 6-29 months (17 +/- 9 months).


RESULTS
GSTT1, GSTM1, GSTO2 and GSTP1 genes presented a similar genotype distribution, but codon 72 of p53 gene wild-type variant was less frequent in ovarian cancer patients than in controls (chi(2); P = 0.0004).


CONCLUSIONS
We were unable to demonstrate any association between the GST genotypes studied and the risk of ovarian cancer but the inheritance of a heterozygous Arg/Pro genotype of p53 increased the risk of ovarian cancer more than 2.5 times (OR = 2.571; 95% CI = 1.453-4.550). There was no association of the studied genes to any clinical or pathological feature of the patients or to their response to chemotherapy.
Morari
Elaine Cristina
EC
Laboratory of Cancer Molecular Genetics, Department of Medicine, Medical Sciences Faculty, State University of Campinas-UNICAMP, Tessalia Vieira de Camargo 126, 13084-970, Campinas, São Paulo, Brazil.
Lima
Andre Bacellar Costa
AB
Bufalo
Natassia Elena
NE
Leite
Janaina Luisa
JL
Granja
Fabiana
F
Ward
Laura Sterian
LS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001120:Arginine; D003062:Codon; D004198:Disease Susceptibility; D005260:Female; D016158:Genes, p53; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D011392:Proline; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D001120:Arginine; D003062:Codon; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D011392:Proline; C413545:glutathione S-transferase T1; C492569:GSTO2 protein, human; C496556:GSTP1 protein, human