Constitutively Decreased TGFBR1 Allelic Expression is a Common Finding in Colorectal Cancer and is Associated with Three TGFBR1 SNPs

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2010 May 27

PMID 20500843

Citations 16

Authors

Boris Pasche

Kari B Wisinski

Maureen Sadim

Virginia Kaklamani

Michael J Pennison

Qinghua Zeng

Naresh Bellam

Jacquelyn Zimmerman

Nengjun Yi

Kui Zhang

John Baron

Daniel O Stram

M Geoffrey Hayes

Affiliations

Soon will be listed here.

Abstract

Purpose: Constitutively decreased TGFBR1 allelic expression is emerging as a potent modifier of colorectal cancer risk in mice and humans. This phenotype was first observed in mice, then in lymphoblastoid cell lines from patients with microsatellite stable colorectal tumors.

Patients And Methods: We assessed the frequency of constitutively decreased TGFBR1 allelic expression and association with SNPs covering the TGFBR1 locus using RNA and DNA extracted from the peripheral blood lymphocytes of 118 consecutive patients with biopsy-proven adenocarcinoma of the colon or the rectum.

Results: We found that 11(9.3%) of 118 patients exhibited decreased TGFBR1 allelic expression (TGFBR1 ASE). TGFBR1 ASE was strongly associated with three SNPs in linkage disequilibrium with each other: rs7034462 (p = 7.2 x 10-4), TGFBR1*6A (p = 1.6 x 10-4) and rs11568785 (p = 1.4 x 10-4).

Conclusion: These results confirm the high prevalence of constitutively decreased TGFBR1 allelic expression among patients with colorectal cancer. The association of this phenotype with TGFBR1*6A, rs7034462 and rs1156875 suggests an association between TGFBR1 SNPs and colorectal cancer, which warrants additional studies.

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