ABSTRACT
The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Polymorphism, Genetic/genetics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/genetics , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , Carcinoma, Medullary/genetics , Carcinoma, Medullary/mortality , Carcinoma, Medullary/pathology , Croatia , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Survival RateABSTRACT
A case-control retrospective association study was conducted to investigate a possible association of the TP53 polymorphisms, Arg72Pro and PIN3 (+16bp), with sporadic breast cancer in Croatian women. Ninety-five women with breast cancer and 108 age-matched healthy women were analyzed. Arg72Pro polymorphism was detected by TaqMan essay. For designation of PIN3 (+16bp) polymorphism DNA amplification was performed by the polymerase chain reaction (PCR) while the PCR products were detected by capillary electrophoresis. Homozygous genotype of minor allele of the PIN3 (+16bp) polymorphism was associated with sporadic breast cancer (OR = 2.15, 95% confidence interval [CI] 1.80-2.56, p = 0.006). For Arg72 polymorphism, the odds ratio for breast cancer of ArgPro versus reference genotype ArgArg was 0.55 (95% CI 0.30-1.02, p = 0.039) suggesting the protective effect. Although different haplotypes did not influence the susceptibility to the disease, the joint occurrence of genotype combination ProPro/A2A2 frequent in cases, was associated with sporadic breast cancer (OR = 2.20, 95% CI 1.89-2.56, p = 0.021). The study provides evidence of the association of the TP53 gene polymorphisms Arg72Pro and PIN3 (+16bp) with sporadic breast cancer in the Croatian population.
