Journal Article

Polymorphisms in genes involved in GH1 release and their association with breast cancer risk

Kerstin Wagner, Kari Hemminki, Ewa Grzybowska, Rüdiger Klaes, Barbara Burwinkel, Peter Bugert, Rita K. Schmutzler, Barbara Wappenschmidt, Dorota Butkiewicz, Jolanta Pamula, Wioletta Pekala and Asta Försti

in Carcinogenesis

Volume 27, issue 9, pages 1867-1875
ISSN: 0143-3334
Published online April 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl036
Polymorphisms in genes involved in GH1 release and their association with breast cancer risk

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  • Clinical Cytogenetics and Molecular Genetics

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The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1) release is under the influence of three pituitary hormones [growth hormone releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an autocrine/paracrine fashion in the breast. By binding to their respective receptors, they control cell proliferation, differentiation and apoptosis in a GH1/IGF-1-dependent manner. We investigated single nucleotide polymorphisms (SNPs) in the GHRH, GHRHR, GHRL, GHSR, SST and SSTR2 gene regions in a Polish and a German cohort of 798 breast cancer cases and 1011 controls. Our study revealed an association of a novel TC repeat polymorphism in the SST promoter with a decreased breast cancer risk in the Polish study population [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.44–0.96]. The closely linked SNP IVS1 A+46G showed the same trend. For both polymorphisms the association was stronger in women above the age of 50 (OR, 0.33; 95% CI, 0.14–0.76 and OR, 0.39; 95% CI, 0.18–0.87, respectively). The protective effect of these polymorphisms was confirmed in a haplotype analysis among women above 50 years of age and carrying the two variant alleles (OR, 0.37; 95% CI, 0.17–0.80). In the independent German population, we observed slightly decreased ORs among women above the age of 50 years. In the SSTR2 gene, carriers of the promoter 21/21 TG repeat genotype were at a decreased breast cancer risk (OR, 0.62; 95% CI, 0.41–0.94) compared to carriers of the other genotypes in the Polish population. Furthermore, we identified a protective effect of the GHRHR C-261T SNP in both populations (joint analysis CT+TT versus CC: OR, 0.80; 95% CI, 0.65–0.99). This effect was carried by a haplotype containing the protective allele. Thus, our study concludes a possible protective influence of distinct polymorphisms in genes involved in GH1 release on breast cancer risk.

Journal Article.  6946 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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