title: Effect of TP53 16-bp and β-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer.
abstract: P53 as a tumor suppressor and an apoptosis modulator, is the regulator of the cell cycle and apoptosis, and contributes to mammary gland development and breast cancer (BC) progression. BTRC gene (Homo sapiens beta-transducing repeat containing E3 ubiquitin protein ligase) encoded protein, β-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16 bp (rs17878362) and β-TrCP 9 bp (rs16405) INS/DEL polymorphisms on BC risk in an Iranian population. A total of 439 women including 236 BC patients and 203 healthy women were recruited. The TP53 and β-TrCP INS/DEL polymorphisms were genotyped by allele-specific polymerase chain reaction method. Our data demonstrated that the TP53 16-bp INS/DEL variation was associated with an increased risk of BC in codominant (INS/INS vs.
  OR=1.82; 95% CI=1.02-3.23; P=0.042) and dominant (Del/INS+INS/INS vs.
  OR=1.48; 95% CI=1.03-2.21; P=0.044) models. Additionally, the variant allele (INS) of TP53 DEL/INS polymorphism with a relatively higher frequency in cases than in controls (35.6 vs. 27.8) was a risk factor for BC (OR=1.43; 95% CI=1.06-1.93; P=0.017). With respect to β-TrCP INS/DEL polymorphism, our study failed to find any difference in allele and genotype distribution between BC patients and controls in codominant, dominant and recessive tested inheritance models (P>0.05). Furthermore, no significant association among the β-TrCP and TP53 genotype distribution and clinical characteristics of BC patients were found (P>0.05). Our findings suggest that the TP53 16-bp INS/INS and DEL/INS+INS/INS genotypes as well as the INS allele could be genetic factors related to BC risk.
authors.affiliation: Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
authors.affiliation: Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Electronic address: mhd.hashemi@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Shadi
authors.initials: S
authors.lastname: Amininia
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rezaei
authors.affiliation: Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Hashemi
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics*
chemical_list: C471644:BTRC protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044844:beta-Transducin Repeat-Containing Proteins
keywords: Breast cancer; Deletion polymorphism; TP53; β-TrCP