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CYP17 & SULT1A1 gene polymorphisms in Indian breast cancer

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Abstract

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.

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References

  1. McKean-Cowdin R, Feigelson HS, Pike MC, Coetzee GA, Kolonel LN, Henderson BE: Risk of endometrial cancer and estrogen replacement therapy history by CYP17 Genotype.Cancer Res 61:848–849, 2001.

    PubMed  CAS  Google Scholar 

  2. Luft FC: Steroidogenesis and CYP enzymes.J Mol Med 79:549–550, 2001.

    Article  PubMed  CAS  Google Scholar 

  3. Carey AH, 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.Hum Mol Genet 3:1873–1876, 1994.

    Article  PubMed  CAS  Google Scholar 

  4. Kadonaga JT, Jones KA, Tijan R: Promoter specific activation of RNA polymerase II transcription by Spl.Trends Biochem Sci 11:20–23, 1986.

    Article  CAS  Google Scholar 

  5. Eaton NE, Reeves GK, Appleby PN, Key TJ: Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies.Br J Cancer 80:930–934, 1999.

    Article  PubMed  CAS  Google Scholar 

  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 36:2375–2379, 2000.

    Article  PubMed  CAS  Google Scholar 

  7. Glatt H: Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation.FASEB J 11:314–321, 1997.

    PubMed  CAS  Google Scholar 

  8. Weinshilboum RM, Otterness DM, Aksoy IA, Wood TC, Her C, Raftogianis RB: Sulfation and sulfotransferases 1: sulfotransferase molecular biology: cDNAs and genes.FASEB J 11:3–14, 1997.

    PubMed  CAS  Google Scholar 

  9. Dooley TP, Huang Z: Genomic organization and DNA sequences of two human phenol sulfotransferases genes (STP1 and STP2) on the short arm of chromosome 16.Biochem Biophys Res Commun 228:134–140, 1996.

    Article  PubMed  CAS  Google Scholar 

  10. Glatt H, Boeing H, Engelke CEH, Ma L, Kuhlow A, Pabel U, Pomplun D, Teubner W, MeinlW: Human cytosolic transferases: genetics, characteristics, toxicological aspects.Mutat Res 482:27–40, 2001.

    PubMed  CAS  Google Scholar 

  11. Coughtrie MWH, Gilissen RAHJ, Shek B, Strange RC, Fryer AA, Jones PW, Bamber DE: Phenol sulfotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations.Biochem J 337:45–49, 1999.

    Article  PubMed  CAS  Google Scholar 

  12. Raftogianis RB, Wood TC, Weinshilboum RM: Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozymes properties and human liver genotype-phenotype correlations.Biochem Pharmacol 58:605–616, 1999.

    Article  PubMed  CAS  Google Scholar 

  13. Weston A, Pan C, Bleiweiss IJ, Ksieski HB, Roy N, Maloney N, Wolff MS: CYP17 genotype and breast cancer risk.Cancer Epidemiol Biomarkers Prev 7:941–944, 1998.

    PubMed  CAS  Google Scholar 

  14. Zheng W, Xie D, Cerhan JR, Sellers TA, Wen W, Folsom AR: Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake and breast cancer risk.Cancer Epidemiol Biomarkers Prev 10:89–94, 2001.

    PubMed  Google Scholar 

  15. Feigelson HS, Henderson BE: Estrogens and breast cancer.Carcinogenesis 17:2279–2284, 1996.

    Article  PubMed  CAS  Google Scholar 

  16. Sourdaine P, Mullen P, White R, Telford J, Parker MG, Miller MR: Aromatase activity and CYP19 gene expression in breast cancers.J Steroid Biochem Mol Biol 59:191–198, 1996.

    Article  PubMed  CAS  Google Scholar 

  17. Khan SA, Rodgers MA, Khurana KK, Meguid MM, Numann PJ: Estrogen receptor expression in benign breast epithelium and breast cancer risk.J Natl Cancer Inst 90:37–42, 1998.

    Article  PubMed  CAS  Google Scholar 

  18. Feigelson HS, Coetzee GA, Kolonel LN, Ross RK, Henderson BE: A polymorphism in the CYP17 gene increases the risk of breast cancer.Cancer Res 57:1063–1065, 1997.

    PubMed  CAS  Google Scholar 

  19. Feigelson HS, Shames LS, Pike MC, Coetzee GA, Stanczyk FZ, Henderson BE: Cytochrome P450 cl7a gene polymorphism is associated with serum estrogen and progesterone concentrations.Cancer Res 58:585–587, 1998.

    PubMed  CAS  Google Scholar 

  20. Haiman CA, Hanikson SE, Spiegelman D, Colditz GA, Willet WC, Speizer FE, Kelsey KT, Hunter DJ: The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer.Cancer Res 59:1015–1020, 1999.

    PubMed  CAS  Google Scholar 

  21. Dunning AM, Healy CS, Pharoah PDP, Foster NA, Lipscombe JM, Redman KL, Easton DF, Day NE, Ponder BAJ: No association between a polymorphism in the steroid metabolism gene CYP17 and risk of breast cancer.Br J Cancer 77:2045–2047, 1998.

    PubMed  CAS  Google Scholar 

  22. Helzlsouer KJ, Huang HY, Strickland PT, Hohhman S, Alberg AJ, Comstock GW, Bell DA: Association between CYP17 polymorphisms and the development of breast cancer.Cancer Epidemiol Biomarkers Prev 7:945–949, 1998.

    PubMed  CAS  Google Scholar 

  23. Young IE, Kurian KM, Annink C, Kunkler IH, Anderson VA, Cohen BB, Hooper ML, Wyllie AH, Steel CM: A polymorphism in the CYP17 gene is associated with male breast cancer.Br J Cancer 81:141–143, 1999.

    Article  PubMed  CAS  Google Scholar 

  24. Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N, Tachiki H, Shimoda N, Satoh S, Sato K, Kakehi Y, Kamoto T, Ogawa O, Kato T: Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect.Cancer Res 60:5710–5713, 2000.

    PubMed  CAS  Google Scholar 

  25. Kittles RA, Ramesh K, Panguluri RK, Chen W, Massac A, Ahaghotu C, Jackson A, Ukoli F, Adams-Campbell L, Isaacs W, Dunston GM: CYP17 promoter variant associated with prostate cancer aggressiveness in African Americans.Cancer Epidemiol Biomarkers Prev 10:943–947, 2001.

    PubMed  CAS  Google Scholar 

  26. Diamanti-Kandarakis E, Bartzis MI, Zapandi ED, Spina GG, Filandra FA, Tsianateli TC, Bergiele AT, Kouli CR: Polymorphism TRC (-34 bp) of gene CYP17 promoter in Greek patients with polycyclic ovary syndrome.Fertil Steril 71:431–435, 1999.

    Article  PubMed  CAS  Google Scholar 

  27. Kristensen VN, Haraldsen EK, Anderson KB, Lonning PE, Erikstein B, Karesen R, Gabrielsen OS, Borresen -Dale A-L: CYP17 and breast cancer risk: the polymorphism in the 5’ flanking area of the gene does not influence binding to SP-I.Cancer Res 59:2825–2828, 1999.

    CAS  Google Scholar 

  28. Nagaya N, Toi M, Sunahara S, Kurimoto F, Tominaga T: Determination of intratumoral estrone (El) and estradiol (E2) in primary breast cancer tissues by sensitive HPLC-RIA.Gan To Kagaku Ryoho 24:329–336 1997

    PubMed  CAS  Google Scholar 

  29. Carlini EJ, Raftogianis RB, Wood TC, Jin F, Zheng W, Rebbeck TR, Weinshilboum RM: Sulfation pharmacogenetics: SULT1A1 AND SULT1A2 frequencies in Caucasian, Chinese and African-American subjects.Pharmacogenetics 11:57–68, 2001.

    Article  PubMed  CAS  Google Scholar 

  30. Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY: Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility.Cancer Res 59:4870–4875, 1999.

    PubMed  CAS  Google Scholar 

  31. Feigelson HS, McKean-Cowdin R, Coetzee GA, Stram DO, Kolonel LN, Henderson BE: Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates.Cancer Res 61:785–789, 2001.

    PubMed  CAS  Google Scholar 

  32. Guillemette C, De Vivo I, Hankinson SE, Haiman CA, Spiegelman D, Housman DE, Hunter DJ: Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels.Cancer Epidemiol Biomarkers Prev 10:711–714, 2001.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Molecular Medicine, Drug Development & Chemoinformatics, Regional Cancer Centre, Thiruvananthapuram, India

    Priya Chacko, Thomas Joseph & M Radhakrishna Pillai

  2. Breast Specialty Clinic, Regional Cancer Centre, Thiruvananthapuram, India

    Balakrishnan Rajan & Beela Sarah Mathew

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  1. Priya Chacko
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  2. Balakrishnan Rajan
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  3. Beela Sarah Mathew
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  4. Thomas Joseph
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  5. M Radhakrishna Pillai
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Correspondence to M Radhakrishna Pillai.

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Chacko, P., Rajan, B., Mathew, B.S. et al. CYP17 & SULT1A1 gene polymorphisms in Indian breast cancer. Breast Cancer 11, 380–388 (2004). https://doi.org/10.1007/BF02968046

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  • DOI: https://doi.org/10.1007/BF02968046

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