Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study

Montserrat Garcia-Closas, Louise A Brinton, Jolanta Lissowska, Douglas Richesson, Mark E Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Robert Welch, Meredith Yeager, Witold Zatonski, Stephen J Chanock, Montserrat Garcia-Closas, Louise A Brinton, Jolanta Lissowska, Douglas Richesson, Mark E Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Robert Welch, Meredith Yeager, Witold Zatonski, Stephen J Chanock

Abstract

Background: The sex hormone-binding globulin (SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer.

Methods: The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region.

Results: None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and -67G>A 5'UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG.

Conclusion: These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk.

References

    1. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst. 1998;90:1774–1786. doi: 10.1093/jnci/90.23.1774.
    1. Lukanova A, Lundin E, Akhmedkhanov A, Micheli A, Rinaldi S, Zeleniuch-Jacquotte A, Lenner P, Muti P, Biessy C, Krogh V, Berrino F, Hallmans G, Riboli E, Kaaks R, Toniolo P. Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer. 2003;104:636–642. doi: 10.1002/ijc.10990.
    1. Helzlsouer KJ, Alberg AJ, Gordon GB, Longcope C, Bush TL, Hoffman SC, Comstock GW. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA. 1995;274:1926–1930. doi: 10.1001/jama.274.24.1926.
    1. Selby C. Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Biochem. 1990;27 ( Pt 6):532–541.
    1. Cousin P, Calemard-Michel L, Lejeune H, Raverot G, Yessaad N, Emptoz-Bonneton A, Morel Y, Pugeat M. Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. J Clin Endocrinol Metab. 2004;89:917–924. doi: 10.1210/jc.2002-021553.
    1. Dunning AM, Dowsett M, Healey CS, Tee L, Luben RN, Folkerd E, Novik KL, Kelemen L, Ogata S, Pharoah PD, Easton DF, Day NE, Ponder BA. Polymorphisms associated with circulating sex hormone levels in postmenopausal women. J Natl Cancer Inst. 2004;96:936–945.
    1. Haiman CA, Riley SE, Freedman ML, Setiawan VW, Conti DV, Le Marchand L. Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating shbg levels among postmenopausal women: the Multiethnic Cohort. J Clin Endocrinol Metab. 2005;90:2198–2204. doi: 10.1210/jc.2004-1417.
    1. A L, L B, YM LV, S P, Gerhadt D. Tarazona-Santos. D GR, PE L, VN K, S C. Pattern of genetic variation in the TP53 locus indicates linkage disequilibrium extends across the flanking genes, ATP1B2 and WDR79. 2007.
    1. BR P, Yeager M. L B, R W, M B, L Q, Sicotte H. B S, M A, A C, A E, V P, DS G, SJ C. SNP500Cancer: A Public Resource for Sequence Validation, Assay Development, and Frequency Analysis for Genetic Variation in Candidate Genes. Nuc Acids Res. 2006;34 (Database Issue):D617–D621.
    1. 2007.
    1. Webb PM, Green A, Cummings MC, Purdie DM, Walsh MD, Chenevix-Trench G. Relationship between number of ovulatory cycles and accumulation of mutant p53 in epithelial ovarian cancer. J Natl Cancer Inst. 1998;90:1729–1734. doi: 10.1093/jnci/90.22.1729.
    1. 2007.
    1. Schaid DJ. Evaluating associations of haplotypes with traits. Genet Epidemiol. 2004;27:348–364. doi: 10.1002/gepi.20037.
    1. 2007.
    1. NS W, LS C, DC F, KA R. Ovarian Cancer. In: D S and JF F, editor. Cancer Epidemiology and Prevention. New York, Oxford University Press; 1996. pp. 1040–1057.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren