| 3'-UTR and functional secretor haplotypes in mannose-binding lectin 2 are associated with increased colon cancer risk in African Americans. | |
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MedLine Citation:
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PMID: 22282660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Because chronic intestinal inflammation is a risk factor for colorectal cancer, we hypothesized that genetic variants of inflammatory mediators, such as mannose-binding lectin 2 (MBL2), are associated with colon cancer susceptibility. Here, we report the association of 24 MBL2 single-nucleotide polymorphisms (SNP) and corresponding haplotypes with colon cancer risk in a case-control study. Four SNPs in the 3'-untranslated region (UTR) of the gene (rs10082466, rs2120132, rs2099902, and rs10450310) were associated with an increased risk of colon cancer in African Americans. ORs for homozygous variants versus wild-type ranged from 3.17 [95% confidence interval (CI), 1.57-6.40] to 4.51 (95% CI, 1.94-10.50), whereas the 3'-UTR region haplotype consisting of these four variants had an OR of 2.10 (95% CI, 1.42-3.12). The C allele of rs10082466 exhibited a binding affinity of miR-27a and this allele was associated with both lower MBL plasma levels and activity. We found that 5' secretor haplotypes known to correlate with moderate and low MBL serum levels exhibited associations with increased risk of colon cancer in African Americans, specifically as driven by two haplotypes, LYPA and LYQC, relative to the referent HYPA haplotype (LYPA: OR, 2.60; 95% CI, 1.33-5.08 and LYQC: OR, 2.28; 95% CI, 1.20-4.30). Similar associations were not observed in Caucasians. Together, our results support the hypothesis that genetic variations in MBL2 increase colon cancer susceptibility in African Americans. |
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Authors:
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Krista A Zanetti; Majda Haznadar; Judith A Welsh; Ana I Robles; Bríd M Ryan; Andrew C McClary; Elise D Bowman; Julie E Goodman; Toralf Bernig; Stephen J Chanock; Curtis C Harris |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2012-01-26 |
Journal Detail:
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Title: Cancer research Volume: 72 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-16 Completed Date: 2012-05-14 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 1467-77 Citation Subset: IM |
Affiliation:
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Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions
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genetics Adult African Continental Ancestry Group / genetics*, statistics & numerical data Aged Case-Control Studies Colonic Neoplasms / epidemiology, genetics* European Continental Ancestry Group / genetics, statistics & numerical data Female Genetic Association Studies Genetic Predisposition to Disease* Haplotypes* Humans Male Mannose-Binding Lectin / blood, genetics* Middle Aged Polymorphism, Genetic Polymorphism, Single Nucleotide Risk |
| Grant Support | |
ID/Acronym/Agency:
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Z01 BC005480-22/BC/NCI NIH HHS; ZIA BC010033-15/BC/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/MBL2 protein, human; 0/Mannose-Binding Lectin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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