CYP17 & SULT1A1 gene polymorphisms in Indian breast cancer

被引:26
作者
Chacko P. [1 ]
Rajan B. [2 ]
Mathew B.S. [2 ]
Joseph T. [1 ]
Pillai M.R. [1 ]
机构
[1] Division of Molecular Medicine, Drug Development and Chemoinformatics, Regional Cancer Centre, Thiruvananthapuram 695011, Kerala State
[2] Breast Specialty Clinic, Regional Cancer Centre, Thiruvananthapuram
关键词
Breast cancer; CYP17; MspAl; Polymorphism; SULT1A1;
D O I
10.1007/BF02968046
中图分类号
学科分类号
摘要
Background: Breast cancer is the most common cancer among women worldwide. Life-time exposure to steroid hormones, especially estrogen, is a major risk factor for breast cancer. Functional polymorphisms in genes encoding steroid metabolizing enzymes may thus be important as biomarkers of individual susceptibility to breast cancer. The CYP17 and SULT1A1 genes encode for two enzymes involved in hormone biosynthesis and metabolism. Single nucleotide polymorphisms of these genes may result in inter-individual variability in steroid hormone biosynthesis and metabolism thus influence the development of breast cancer. Methods: We tested this hypothesis by conducting a case - control study on a group of 140 breast cancer cases and 140 healthy age-matched controls. Analysis of CYP17 & SULT1A1 genotypes were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: The genetic polymorphisms of the estrogen-related genes SULT1A1 (OR = 2.5, 95% CI = 1.28-4.98) and CYP17 (OR = 4.1, 95% CI = 1.78-9.63) were associated with an increased risk of breast cancer among postmenopausal women. Our data also showed evidence for the genetic regulation of serum 17β estradiol (E2) levels as measured by ELISA among the premenopausal women with a significant increase in the serum E2 level for the CYP17 A2 variants. Conclusion: These results suggest that both CYP17 and SULT1A1 genotypes could be important determinants of breast cancer risk in Indian women and may help in early identification of high risk subjects. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening, diagnosis and therapeutic intervention in breast cancer.
引用
收藏
页码:380 / 388
页数:8
相关论文
共 32 条
[1]  
McKean-Cowdin R., Feigelson H.S., Pike M.C., Coetzee G.A., Kolonel L.N., Henderson B.E., Risk of endometrial cancer and estrogen replacement therapy history by CYP17 genotype, Cancer Research, 61, 3, pp. 848-849, (2001)
[2]  
Luft F.C., Steroidogenesis and CYP enzymes, Journal of Molecular Medicine, 79, 10, pp. 549-550, (2001)
[3]  
Carey A.H., Waterworth D., Patel K., White D., Little J., Novelli P., Franks S., Williamson R., Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17, Human Molecular Genetics, 3, 10, pp. 1873-1876, (1994)
[4]  
Kadonaga J.T., Jones K.A., Tijan R., Promoter specific activation of RNA polymerase II transcription by Spl, Trends Biochem Sci, 11, pp. 20-23, (1986)
[5]  
Eaton N.E., Reeves G.K., Appleby P.N., Key T.J., Endogenous sex hormones and prostate cancer: A quantitative review of prospective studies, British Journal of Cancer, 80, 7, pp. 930-934, (1999)
[6]  
Miyoshi Y., Iwao K., Ikeda N., Egawa C., Noguchi S., Genetic polymorphism in CYP17 and breast cancer risk in Japanese women, Eur J Cancer, 36, pp. 2375-2379, (2000)
[7]  
Glatt H., Bioactivation of mutagens via sulfation, FASEB Journal, 11, 5, pp. 314-321, (1997)
[8]  
Weinshilboum R.M., Otterness D.M., Aksoy I.A., Wood T.C., Her C., Raftogianis R.B., Sulfotransferase molecular biology: cDNAs and genes, FASEB Journal, 11, 1, pp. 3-14, (1997)
[9]  
Dooley T.P., Huang Z., Genomic organization and DNA sequences of two human phenol sulfotransferase genes (STP1 and STP2) on the short arm of chromosome 16, Biochemical and Biophysical Research Communications, 228, 1, pp. 134-140, (1996)
[10]  
Glatt H., Boeing H., Engelke C.E.H., Ma L., Kuhlow A., Pabel U., Pomplun D., Teubner W., Meinl W., Human cytosolic sulphotransferases: Genetics, characteristics, toxicological aspects, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 482, 1-2, pp. 27-40, (2001)