Abstract
A functional polymorphism at codon 33 (leucine-to-proline, Leu33Pro)/nucleotide 1565 (T-to-C, T1565C) of the integrin β3 has been hypothesized to increase the risk of breast cancer and its metastasis. Three studies have been conducted up to date and the results were contradictory. We used a large population-based age-matched case-control study in German Caucasian women by the age of 50 years to assess breast cancer risk associated with this polymorphism, taking into consideration of possible interaction with other risk factors, and to examine if it affects clinical presentation. Overall, the odds ratios (OR) for breast cancer were not increased in women carrying either allele. However, we observed a differential effect of the Leu33Pro polymorphism by age group when patients were stratified by 45 years of age (p=0.055). Being a carrier of the 33 proline allele was found to be associated with a 32% increased risk (95% Cl=1.0–1.8) for breast cancer compared to the wild-type leucine homozygotes among women age 45 or younger but not in older women. Furthermore, we observed significant dose effect of the 33proline allele (p=0.04), with 30% risk increase per allele (95% Cl=1.0–1.7). Significant evidence was also found for a positive association between 33proline carrier status and increasing axillary node involvement (p=0.048) but neither size nor grading of tumor in this study. Our data suggest that inheritance of the integrin β3 Leu33Pro polymorphism may increase the breast cancer risk by age 45 in the German population.
Similar content being viewed by others
References
GC Tucker (2002) ArticleTitleInhibitors of integrins Curr Opin Pharmacol 2 394–402
GJ Mizejewski (1999) ArticleTitleRole of integrins in cancer: survey of expression patterns Proc Soc Exp Biol Med 222 124–138
JD Hood DA Cheresh (2002) ArticleTitleRole of integrins in cell invasion and migration Nat Rev Cancer 2 91–100
BO’Toole Felding-Habermann B TE BO’Toole JW Smith E Fransvea ZM Ruggeri MH Ginsberg PE Hughes PE Pampori SJ Shattil A Saven BM Mueller (2001) ArticleTitleIntegrin activation controls metastasis in human breast cancer Proc Natl Acad Sci USA 98 1853–1858
JB Bussel TJ Kunicki AD Michelson (2000) Platelets: new understanding of platelet glycoproteins and their role in disease. Hematology (Am Soc Hematol Educ Program) 222–240
F Ayala J Corral R Gonzalez-Conejero I Sanchez JM Moraleda V Vicente (2003) ArticleTitleGenetic polymorphisms of platelet adhesive molecules: association with breast cancer risk and clinical presentation. Breast Cancer Res Treat 80(2): 145–154 80 IssueID2 145–154
SE Bojesen A Tybjaerg-Hansen BG Nordestgaard (2003) ArticleTitleIntegrin beta3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst 95 IssueID15 1150–1157
Q Jin K Hemminki E Grzybowska R Klaes M Soderberg A Forsti (2004) ArticleTitleRe: Integrin beta3 Leu33Pro homozygosity and risk of cancer [letter]. J Natl Cancer Inst 96(3): 234–235 96 IssueID3 234–235
JS Bennett F Catella-Lawson AR Rut G Vilaire W Qi SC Kapoor S Murphy GA FitzGerald (2001) ArticleTitleEffect of the Pl(A2) alloantigen on the function of beta(3)-integrins in platelets Blood 97 3093–3099
G Andrioli P Minuz P Solero S Pincelli R Ortolani S Lussignoli P Bellavite (2000) ArticleTitleDefective platelet response to arachidonic acid and thromboxane A(2) in subjects with PlA2 polymorphism of beta(3) subunit (glycoprotein IIIa) Br J Haematol 110 911–918
AD Michelson MI Furman P Goldschmidt-Clermont MA Mascelli C Hendrix L Coleman J Hamlington MR Barnard T Kickler DJ Christie S Kundu PF Bray (2000) ArticleTitlePlatelet GP IIIa PlA polymorphisms display different sensitivities to agonists Circulation 101 1013–1018
A Szczeklik A Undas M Sanak M Frolow W Wegrzyn (2000) ArticleTitleRelationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa Br J Haematol 110 965–967
A Undas K Brummel J Musial KG Mann A Szczeklik (2001) ArticleTitlePl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury Circulation 104 2666–2672
D Feng K Lindpaintner MG Larson VS Rao CJ O’Donnell I Lipinska C Schmitz PA Sutherland H Silbershatz RB D’Agostino JE Muller RH Myers D Levy GH Tofler (1999) ArticleTitleIncreased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study Arterioscler Thromb Vasc Biol 19 1142–1147
KV Vijayan Y Liu JF Dong PF Bray (2003) ArticleTitleEnhanced activation of mitogenactivated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin beta 3 J Biol Chem 278 3860–3867
J Chang-Claude N Eby M Kiechle G Bastert H Becher (2000) ArticleTitleBreastfeeding and breast cancer risk by age 50 among women in Germany. Cancer Causes Control 11 IssueID8 687–695
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang-gohrke, S., Chang-claude, J. Integrin β3 Leu33Pro polymorphism and breast cancer risk: a population-based case-control study in Germany. Breast Cancer Res Treat 88, 231–237 (2004). https://doi.org/10.1007/s10549-004-0782-5
Issue Date:
DOI: https://doi.org/10.1007/s10549-004-0782-5