TβR-I(6A) is a candidate tumor susceptibility allele Journal Article


Authors: Pasche, B.; Kolachana, P.; Nafa, K.; Satagopan, J.; Chen, Y. G.; Lo, R. S.; Brener, D.; Yang, D.; Kirstein, L.; Oddoux, C.; Ostrer, H.; Vineis, P.; Varesco, L.; Jhanwar, S.; Luzzatto, L.; Massagué, J.; Offit, K.
Article Title: TβR-I(6A) is a candidate tumor susceptibility allele
Abstract: We have previously described a type I transforming growth factor (TGF)- β receptor (TβR-I) polymorphic allele, TβR-I(6A), that has a deletion of three alanines from a nine-alanine stretch. We observed a higher than expected number of TβR-I(6A) homozygotes among tumor and nontumor DNA from patients with a diagnosis of cancer. To test the hypothesis that TβR-I(6A) homozygosity is associated with cancer, we performed a case-control study in patients with a diagnosis of cancer and matched healthy individuals with no history of cancer and who were identical in their gender and their geographical and ethnic background to determine the relative germ-line frequencies of this allele. We found nine TβR-I(6A) homozygotes among 851 patients with cancer. In comparison, there were no TβR-I(6A) homozygotes among 735 healthy volunteers (P < 0.01). We also observed an excess of TβR- I(6A) heterozygotes in cancer cases compared to controls (14.6% versus 10.6%; P = 0.02, Fisher's exact test). A subset analysis revealed that 4 of 112 patients with colorectal cancer were TβR-I(6A) homozygotes (P < 0.01). Using mink lung epithelial cell lines devoid of TβR-I, we established stably transfected TβR-I and TβR-I(6A) cell lines. We found that, compared to TβR-I, TβR-I(6A) was impaired as a mediator of TGF-β antiproliferative signals. We conclude that TβR-I(6A) acts as a tumor susceptibility allele that may contribute to the development of cancer, especially colon cancer, by means of reduced TGF-β-mediated growth inhibition.
Keywords: adult; major clinical study; case control study; genetics; case-control studies; neoplasm; neoplasms; colorectal cancer; ovarian neoplasms; metabolism; allele; cancer susceptibility; genetic predisposition to disease; transforming growth factor beta; colonic neoplasms; alleles; gene frequency; transfection; protein serine threonine kinase; breast neoplasms; heterozygote; carcinogenesis; germ line; homozygosity; genetic transfection; protein-serine-threonine kinases; colon tumor; breast tumor; ovary tumor; homozygote; transforming growth factor beta receptor; receptors, transforming growth factor beta; analysis of variance; genetic predisposition; germ cell tumor; deletion mutant; ethnology; germinoma; activin receptors, type i; humans; human; male; female; priority journal; article; activin receptor 1; tgf beta type i receptor; tgf-beta type i receptor
Journal Title: Cancer Research
Volume: 59
Issue: 22
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1999-11-15
Start Page: 5678
End Page: 5682
Language: English
PUBMED: 10582683
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus