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Abstract

Title: Lack of association of transforming growth factor-beta1 polymorphisms and haplotypes with prostate cancer risk in the prostate, lung, colorectal, and ovarian trial.
Author: Kang D, Lee KM, Park SK, Berndt SI, Reding D, Chatterjee N, Welch R, Chanock S, Huang WY, Hayes RB
Journal: Cancer Epidemiol Biomarkers Prev 16(6):1303-1305
Year: 2007
Month: June

Abstract: Transforming growth factor h (TGF-h) plays a key role in cell cycle control and carcinogenic processes. TGF-h regulates growth and proliferation of cells and may play a dual role in carcinogenesis, inhibiting early-stage growth and promoting later-stage growth (1). TGF-h1, the predominant TGF-h, stimulates cell differentiation and inhibits epithelial cell proliferation in nonmalignant prostate cells; however, prostate cancer cells exhibit resistance to the growth-inhibitory effect of TGF-h1 (2). Gene variants in TGFB1 have been related to functional effects. Thus, the gene would seem to be a good prostate cancer susceptibility candidate (2). The TGFB1 10Pro (C) and tightly linked _509T alleles are reported to increase levels of TGF-h1 (3-6). The _800A polymorphism is expected to reduce the affinity for the cAMP responsive element binding protein family of transcription factors and, thus, to decrease expression of TGF-h1 (4). The Arg-to-Pro polymorphism at codon 25 was associated with lower TGF-h1 production (7, 8). The Thr-to-Ile polymorphism at codon 263 is located in the part of the TGF-h1 pro-protein that is cleaved from the active part of the protein and may thus affect TGF-h1 activation (9). Japanese males with the TGFB1 TC (Leu/Pro) or TT (Leu/Leu) genotype at codon 10 (+29 position) were reported to have a 1.6 fold increased risk for prostate cancer (10), and American physicians were reported to have a 2.4-fold increased risk for advanced stage prostate cancer in relation to the T allele at TGFB1 position _509, whereas no excess was noted for the codon 10 variant (11). In the Prostate, Lung, Colorectal, and Ovarian(PLCO) Cancer Screening Trial, we investigated the role of five singlenucleotide polymorphisms (SNP) in TGFB1, chosen because of potential functional significance, in relation to prostate cancer risk. We studied >1,300 prostate cancer cases and a similar number of controls.