Journal Article

The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer

Kerstin Wagner, Kari Hemminki, Ewa Grzybowska, Rüdiger Klaes, Dorota Butkiewicz, Jolanta Pamula, Wioletta Pekala, Helena Zientek, Danuta Mielzynska, Ewa Siwinska and Asta Försti

in Carcinogenesis

Volume 25, issue 12, pages 2473-2478
Published in print December 2004 | ISSN: 0143-3334
Published online December 2004 | e-ISSN: 1460-2180 | DOI:
The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer

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The insulin-like growth factor 1 (IGF-1) pathway plays an important role in regulating cell proliferation, differentiation and apoptosis. IRS1, IRS2 and SHC1 are the key mediators for the downstream pathway processes. Genetic variation within these genes may lead to altered signalling. We screened IRS1, IRS2 and SHC1 for published coding region polymorphisms and choose five of them, IRS1 Ala804Ala and Gly972Arg, IRS2 Cys816Cys and Gly1057Asp and SHC1 Met300Val, for further analysis. We studied the association of the polymorphisms with breast cancer risk using a case–control design with Polish familial breast cancer cases and respective controls. For the polymorphisms in IRS1 and IRS2 no differences in the allele, genotype or haplotype distributions could be detected between the case and control subjects. Carriers of the variant allele of the SHC1 polymorphism were at decreased risk of breast cancer (OR 0.54, 95% CI 0.32–0.90, P = 0.016). A non-significant trend for a protective effect of the SHC1 Val300 allele was also seen in an independent population consisting of German familial breast cancer cases and matched controls. The joint analysis after Mantel–Haenzsel adjustment of the two populations gave an OR of 0.62 (95% CI 0.41–0.93, P = 0.02) for the SHC1 Val300 carriers. A stronger effect was detected in women diagnosed below the age of 50 (OR 0.54, 95% CI 0.32–0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk.

Keywords: 95% CI, 95% confidence interval; GRB2, growth factor receptor bound protein 2; IGF-1, insulin-like growth factor-1; IGFBPs, insulin-like growth factor binding proteins; IRS, insulin receptor substrate; OR, odds ratios; PI, phosphatidylinositol; RFLP, restriction fragment length polymorphism; SH2, Scr homology 2; SHC1, Src homology 2 domain-containing transforming protein 1; SNPs, single nucleotide polymorphisms

Journal Article.  4993 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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