S Dholariya1, R Mir2, M Zuberi3, P Yadav4, G Gandhi5, N Khurana6, A Saxena7, P C Ray8. 1. Department of Biochemistry, R.D. Gardi Medical College, Ujjain, 456006, MP, India. drsagar.dholariya@gmail.com. 2. Cancer Molecualr Genetics, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair, University of Tabuk, Tabuk, Saudi Arabia, 71491, Saudi Arabia. rashidaiims@gmail.com. 3. Molecular Oncology Lab, Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. mariyam13mamc@gmail.com. 4. Molecular Oncology Lab, Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. prashantbiochemist007@gmail.com. 5. Department of Obstetrics and Gynecology, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. ggandhi2004@yahoo.co.in. 6. Department of Pathology, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. nitakhurana@rediffmail.com. 7. Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. alpanasaxena@hotmail.com. 8. Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. drpcraymamc@gmail.com.
Abstract
BACKGROUND: In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. OBJECTIVES: This study aimed at exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene-gene interaction of these two polymorphisms with risk of developing EOC. MATERIALS: The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. RESULTS: We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). CONCLUSIONS: The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.
BACKGROUND: In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. OBJECTIVES: This study aimed at exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene-gene interaction of these two polymorphisms with risk of developing EOC. MATERIALS: The study was conducted on 70 Epithelial ovarian cancerpatients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. RESULTS: We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53Arg/Pro genotypes = 8.7, 95 % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). CONCLUSIONS: The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.
Entities:
Keywords:
B-cell lymphoma 2-associated X protein; Epithelial ovarian cancer; Single-nucleotide polymorphism; Tumor protein 53
Authors: P Perego; M Giarola; S C Righetti; R Supino; C Caserini; D Delia; M A Pierotti; T Miyashita; J C Reed; F Zunino Journal: Cancer Res Date: 1996-02-01 Impact factor: 12.701