Carcinogenesis Advance Access published online on April 10, 2006
Carcinogenesis, doi:10.1093/carcin/bgl036
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1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
* To whom correspondence should be addressed. The regulation of GH1 and IGF-1 release is under the influence of three pituitary hormones (GHRH, GHRL and 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 totally 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 (OR 0.65, 95% 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 vs. 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.
Received January 12, 2006
Revised March 23, 2006
Accepted March 31, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphisms in genes involved in GH1 release and their association with breast cancer risk
Kerstin Wagner 1 *,
Kari Hemminki 2,
Ewa Grzybowska 3,
Rüdiger Klaes 4,
Barbara Burwinkel 1,
Peter Bugert 5,
Rita K. Schmutzler 6,
Barbara Wappenschmidt 6,
Dorota Butkiewicz 3,
Jolanta Pamula 3,
Wioletta Pekala 3,
and
Asta Försti 2
2 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden
3 Department of Molecular Biology, Centre of Oncology, Maria Sklodowska-Curie Institue, Gliwice, Poland
4 Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
5 Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-Hessia, University of Heidelberg, Faculty of Clinical Medicine, Mannheim, Germany
6 Division of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Germany; Center of Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Germany
Kerstin Wagner, E-mail: K.Wagner{at}dkfz.de
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