© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
Re: Integrin 
3 Leu33Pro Homozygosity and Risk of Cancer
Affiliations of authors: Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden (QJ, KH, AF); Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (KH, AF); Department of Tumor Biology, Centre of Oncology, Maria Sklodowska-Curie Institute, Gliwice, Poland (EG); Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany (RK); Department of Pathology, Huddinge Hospital, Huddinge (MS).
Correspondence to: Qianren Jin, MD, Department of Biosciences at Novum, Karolinska Institute, SE-141 57, Huddinge, Sweden (e-mail: qianren.jin{at}cnt.ki.se)
Altered expression of the 
3 integrin gene has been implicated in the metastasis of breast cancer (1). A single-nucleotide polymorphism at codon 33 of the 3 integrin gene that exchanges a leucine (Leu) for a proline (Pro) seems to modify the function of cells expressing 3 integrins [(2) and references therein]. Recently, Bojesen et al. (2) carried out a cohort study on the Leu33Pro polymorphism and showed an increased risk of breast cancer among individuals who were homozygous Pro/Pro carriers of the polymorphism. At almost the same time, Ayala et al. (3) showed an increased risk of breast cancer among individuals who were homozygous Leu/Leu carriers. These observations raise the question of which allele, if any, reflects a true association with an increased risk of breast cancer.
The number of breast cancers in each study (2,3) was small (195 and 101, respectively). We performed a case–control study of 886 women with breast cancer, including 221 postmenopausal women with breast cancer from Finland unselected for family history of breast cancer and 665 women with familial breast cancer from Poland, Germany, and Sweden (4,5). All case subjects were ethnically and geographically matched with control subjects as described (4,5). The German women with breast cancer did not carry mutations in their BRCA1 or BRCA2 genes. Among the women with familial breast cancer, 25% were diagnosed as having bilateral breast cancer. The use of familial cases can substantially increase the power of association studies (6). The study was approved by the ethics committee of the Karolinska Institute Syd. DNA samples were genotyped for the Leu33Pro polymorphism by the polymerase chain reaction and restriction fragment length analysis, as described (7).
The genotype and allele distribution among the breast cancer case and control subjects is shown in Table 1. There was no deviation from the expected Hardy–Weinberg distribution in any group. The frequency of the Pro allele among the control groups was approximately 14%, which is in agreement with the reports regarding the frequency of the allele among Caucasian populations (2,3). We observed no differences in the allele or genotype frequencies between the unselected breast cancer group and the familial breast cancer group. We determined the odds ratios for genotype distribution between the case subjects with breast cancer and control subjects and found no differences in either population. The lack of association remained when the data for the case subjects with familial breast cancer were stratified into two groups by bilateral breast cancer status (data not shown).
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With our sample size, we had a more than 90% power to detect a 1.6-fold increased risk of breast cancer. Because our study was 4.5 times larger than the largest of the published studies (2,3), and because we used mainly familial case subjects, our study provides strong evidence that the
3 integrin Leu33Pro polymorphism does not appreciably modify breast cancer risk.
REFERENCES
1 Felding-Habermann B, O'Toole TE, Smith JW, Fransvea E, Ruggeri ZM, Ginsberg MH, et al. Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A 2001;98:1853–8.
2 Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Integrin beta3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst 2003;95:1150–7.
3 Ayala F, Corral J, Gonzalez-Conejero R, Sanchez I, Moraleda JM, Vicente V. Genetic polymorphisms of platelet adhesive molecules: association with breast cancer risk and clinical presentation. Breast Cancer Res Treat 2003;80:145–54.[CrossRef][Web of Science][Medline]
4 Meindl A. Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Int J Cancer 2002;97:472–80.[CrossRef][Web of Science][Medline]
5 Forsti A, Jin Q, Grzybowska E, Soderberg M, Zientek H, Sieminska M, et al. Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer. Carcinogenesis 2002;23:1315–20.
6 Houlston RS, Peto J. The future of association studies of common cancers. Hum Genet 2003;112:434–5.[Web of Science][Medline]
7 Andrioli G, Minuz P, Solero P, Pincelli S, Ortolani R, Lussignoli S, et al. Defective platelet response to arachidonic acid and thromboxane A(2) in subjects with Pl(A2) polymorphism of beta(3) subunit (glycoprotein IIIa). Br J Haematol 2000;110:911–8.[CrossRef][Web of Science][Medline]
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Del.icio.us What's this?
3 Leu33Pro Homozygosity and Risk of Cancer
J Natl Cancer Inst 2004 96: 235.
3 Leu33Pro Homozygosity and Risk of Cancer
J Natl Cancer Inst 2005 97: 778-779.
3 Leu33Pro Homozygosity and Risk of Cancer
J Natl Cancer Inst 2005 97: 779-780.
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