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 casecontrol 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 HardyWeinberg 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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