Carcinogenesis Advance Access originally published online on October 27, 2006
Carcinogenesis 2007 28(4):828-836; doi:10.1093/carcin/bgl198
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Published by Oxford University Press 2006
The mannose-binding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women
1 Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH) Bethesda, MD, USA
2 Laboratory of Human Carcinogenesis, CCR NCI, NIH, Bethesda, MD, USA
3 Core Genotyping Facility, NCI NIH, Bethesda, MD, USA
*To whom correspondence should be addressed at: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37/Room 3050B, Bethesda, MD 20892-4258, USA. Tel: +1 301 496 4668; Fax: +1 301 496 0497; Email: ambss{at}mail.nih.gov
Common genetic variants in cancer-related genes contribute to breast cancer. The innate immune system plays a crucial role in the immune surveillance against malignancies, thus it is plausible that genetic variations in key genes of the innate immunity such as the mannose-binding lectin (MBL), MBL2, could influence the risk for breast cancer. We investigated the association of MBL2 genotypes with breast cancer and conducted a comprehensive genotype and haplotype analysis of 26 MBL2 single nucleotide polymorphisms (SNPs) in a case–control study of breast cancer [166 African-American (AA) case patients versus 180 controls and 127 Caucasian (CAU) case patients versus 137 controls]. We observed that the A allele of the 3'-UTR SNP Ex4-1067 (NCBI SNP ID: rs10824792) was significantly associated with a decreased disease risk in AA women [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.27–0.81]. Haplotype analysis of MBL2 showed that the frequency of the corresponding 3' haplotype TATAAC (Ex4-1483, Ex4-1067, Ex4-1047, Ex4-901, Ex4-710, 3238bp 3' STP) was lower in cases than controls among AA women (0.15 versus 0.21; P = 0.02) suggesting a protective effect after adjusting for covariates (OR = 0.51, 95% CI = 0.29–0.88, P = 0.018). In conclusion, this study presents preliminary evidence that common genetic variants in the 3'-UTR of MBL2 might influence the risk for breast cancer in AA women, probably in interaction with the 5' secretor haplotypes that are associated with high concentrations of MBL.
Abbreviations: AA, African-American; CAU, Caucasian; MBL, mannose-binding lectin; SNP, single nucleotide polymorphism
Received May 20, 2006; revised October 10, 2006; accepted October 11, 2006.
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