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Functional genetic variations in the IL-23 receptor gene are associated with risk of breast, lung and nasopharyngeal cancer in Chinese populations.
MedLine Citation:
PMID:  23042301     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Interleukin-23 receptor (IL-23R) is a key element in the T-helper 17 (Th17) cell-mediated inflammatory process, which plays an important role in the pathogenesis of cancer. In this study, we examined whether genetic polymorphisms in IL-23R are associated with cancer risk in 4,936 cancer patients and 5,664 control subjects from eastern and southern Chinese populations. We found that the C allele of the rs10889677A>C polymorphism in the 3'UTR of IL-23R was inversely associated with risk of multiple types of cancer, including breast cancer, lung cancer and nasopharyngeal carcinoma. Healthy controls who harbored the rs10889677C allele had significantly decreased cancer risk (OR=0.74, 95%CI=0.71-0.78) compared with those who harbored the rs10889677A allele. Biochemical analysis demonstrated that the rs10889677A allele disrupted the binding site for the microRNA miR-let-7f, thereby increasing the transcription of the IL-23R in vitro and in vivo. Furthermore, cancer-free individuals carrying the rs10889677CC homozygous genotype had a lower proportion of regulatory T cells (Tregs) and a higher T-cell proliferation rate upon stimulation with concanavalin A than individuals carrying the rs10889677AA homozygous genotype. Our findings indicate that the IL-23R rs10889677A>C polymorphism may influence T-cell proliferation, resulting in changes in the levels of Tregs in vivo and modifying cancer susceptibility.
Authors:
Jian Zheng; Lan Jiang; Liyuan Zhang; Lei Yang; Jieqiong Deng; Yonghe You; Na Li; Hongchun Wu; Wei Li; Jiachun Lu; Yifeng Zhou
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-6
Journal Detail:
Title:  Carcinogenesis     Volume:  -     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China.
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