Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma.
Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that has been implicated in the pathogenesis of colorectal neoplasia. To investigate the association between genetic variants in TGFB1 and the risk of colorectal adenoma, we conducted a case-control study of 754 advanced adenoma cases and 769 controls from the baseline screening exam of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma (>or=1 cm, high-grade dysplasia or villous characteristics), and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy. DNA was extracted from blood specimens, and five single-nucleotide polymorphisms in TGFB1 of known or suggested functional significance (-800G>A, -509C>T, Leu10Pro, Arg25Pro and Thr263Ile) were genotyped. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between each polymorphism and adenoma. The high TGFB1 producer genotypes, -509TT and 10Pro/Pro, were associated with an increased risk of colorectal adenoma compared with other genotypes (OR = 1.51, 95% CI: 1.04-2.20 and OR = 1.37, 95% CI: 1.02-1.86, respectively). These increased risks, particularly for -509TT, were greater for persons with multiple adenomas (OR = 1.89, 95% CI: 1.16-3.09, P = 0.01) and individuals with rectal adenoma (OR = 2.95, 95% CI: 1.66-5.26, P = 0.0002). Haplotype analysis revealed similar findings under a recessive model. No associations were observed for polymorphisms at codons 25 and 263. In conclusion, variants that enhance TGFB1 production may be associated with an increased risk of advanced colorectal adenoma.
Berndt
Sonja I
SI
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. berndts@mail.nih.gov
Huang
Wen-Yi
WY
Chatterjee
Nilanjan
N
Yeager
Meredith
M
Welch
Robert
R
Chanock
Stephen J
SJ
Weissfeld
Joel L
JL
Schoen
Robert E
RE
Hayes
Richard B
RB
D000236:Adenoma / Q000235:genetics; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012016:Reference Values; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014481:United States / Q000453:epidemiology
C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1