Comprehensive assessment of variation at the transforming growth factor β type 1 receptor locus and colorectal cancer predisposition

Luis Carvajal-Carmona, Mike Churchman, Carolina Bonilla, Axel Walther, Jeremie H. Lefèvre, David Kerr, Malcolm Dunlop, Richard Houlston, Walter F. Bodmer, Ian Tomlinson

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The role of transforming growth factor β receptor type 1 (TGFBR1) polymorphisms, particularly a coding CGC insertion (rs11466445, TGFBR1*6A/9A) in exon 1, has been extensively investigated in regard to colorectal cancer (CRC) risk. These investigations have generated conflicting results. More recently, allele-specific expression (ASE) of TGFBR1 mRNA has been suggested as predisposing to CRC, with a relative risk of nearly 10-fold and a population attributable risk of ∼10%. Owing to the potential importance of TGFBR1 variants in CRC, we performed a comprehensive examination of tagging SNPs at and around the gene in 3,101 CRC cases and 3,334 controls of northern European ancestry. To test whether rare or subpolymorphic TGFBR1 variants were associated with CRC risk, we sequenced the gene's exons in a subset of patients. We also evaluated TGFBR1 ASE in a panel of CRC cases and controls. Overall, we found no association between TGFBR1 polymorphisms and CRC risk. The rare variant screen did not identify any changes of potentially pathogenic effects. No evidence of greater ASE in cases than controls was detected, and no haplotype around TGFBR1 could account for the ASE reported in other studies. We conclude that neither genetic variation nor ASE at TGFBR1 is likely to be a major CRC risk factor.

Original languageEnglish (US)
Pages (from-to)7858-7862
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - Apr 27 2010
Externally publishedYes


  • Candidate gene
  • Genetic susceptibility
  • Low penetrance
  • TGF signaling
  • Transforming growth factor β receptor type 1 *6A/9A

ASJC Scopus subject areas

  • General


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