title: Genetic polymorphisms of the transforming growth factor-beta1 gene and breast cancer risk: a possible dual role at different cancer stages.
abstract: Transforming growth factor-beta (TGF-beta) inhibits the proliferation of carcinomas in early stages of breast cancer, whereas it promotes tumor growth and metastasis in later stages of cancer. We evaluated a possible association between TGF-beta1 gene polymorphisms and breast cancer risk in a population-based case-control study of Chinese women living in Shanghai, which included 1,127 breast cancer cases and 1,228 population controls. Two polymorphisms, C-509T and T+29C, were in strong linkage disequilibrium. There were no overall differences in the genotype distribution of T+29C polymorphisms of the TGF-beta1 gene among cases and controls. However, the distribution of the high-activity C allele of T+29C polymorphisms differed by cancer stages (P(trend) = 0.02). This allele was associated with decreased risk of early-stage breast cancer [stages 0 and I; odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54-0.99], and the OR was further reduced to 0.66 (95% CI, 0.45-0.96) for those homozygous for this allele (P(trend) = 0.03). On the other hand, the same allele was associated with nonsignificantly increased risk of breast cancer with advanced stages III and IV (OR, 1.33; 95% CI, 0.81-2.18), which differed significantly from that observed for early-stage cancer (P = 0.04). This result suggests a possible dual effect of TGF-beta1 shown by in vitro experiments and provides an explanation for some of the inconsistent findings from previous epidemiologic studies that did not evaluate this association by cancer stage.
authors.affiliation: Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8300, USA.
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1