A case-control study on the effect of p53 and p73 gene polymorphisms on gastric cancer risk and progression.
The p53 protein and its functional homologue p73 share several functions in modulating cell-cycle control and apoptosis. Based on the functional interaction between p53 and p73 in carcinogenesis, we investigated the combined effect of p73 G4C14-to-A4T14 and p53 gene polymorphisms and their interaction with selected environmental factors, on the risk for gastric cancer in a hospital-based case-control study conducted in Italy. The effect of these polymorphisms on cancer progression was also investigated. One hundred and fifteen gastric cancer cases and 295 hospital controls were genotyped for p73 G4C14-to-A4T14, and p53 exon 4 (Arg72Pro), intron 3 and intron 6 polymorphisms. An increased risk for gastric cancer was found to be associated with the inheritance of the p73 homozygous variant genotype among the gastric cancer intestinal histotype (odds ratio (OR)=6.75; 95% confidence interval (95% CI)=1.88-24.24). An effect modification of the p73 variant allele by gender was observed [(OR=2.82; 95%CI=1.24-6.40) among females, versus an OR of 0.70 (95%CI=0.32-1.54) among males; p-value for homogeneity among strata estimates =0.03]. Gene-gene interaction analyses demonstrated that individuals with combined p53 exon 4 and intron 6 variant alleles are borderline significantly protected from gastric cancer (OR=0.52; 95% CI=0.26-1.07; p-value for interaction =0.005), which was confirmed by the haplotype analysis. Finally, a poorer survival was observed among carriers of the variant allele of p53 intron 6 if compared with those carrying both wild-type alleles (p-value for log-rank test =0.02). This study shows that the p73 G4C14-to-A4T14 polymorphism may be a risk factor for gastric cancer, as reported from other studies in different tumour sites among Caucasians. Along with the protective effect of p53 exon 4-intron 6 allelic variants, already noted for breast and lung cancer, our results require confirmation from larger studies.
De Feo
Emma
E
Genetic Epidemiology and Molecular Biology Unit, Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy. emmadefeo@yahoo.it
Persiani
Roberto
R
La Greca
Antonio
A
Amore
Rosarita
R
Arzani
Dario
D
Rausei
Stefano
S
D'Ugo
Domenico
D
Magistrelli
Paolo
P
van Duijn
Cornelia M
CM
Ricciardi
Gualtiero
G
Boccia
Stefania
S
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53