title: The mannose-binding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women.
abstract: 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.
authors.affiliation: Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH) Bethesda, MD 20892-4258, USA.
authors.forename: Toralf
authors.initials: T
authors.lastname: Bernig
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Boersma
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Howe
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Sunita
authors.initials: S
authors.lastname: Yadavalli
authors.forename: Brian
authors.initials: B
authors.lastname: Staats
authors.forename: Leah E
authors.initials: LE
authors.lastname: Mechanic
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001741:Black or African American / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D005819:Genetic Markers; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin