TGFBR1*6A and cancer risk: A meta-analysis of seven case-control studies

Virginia G. Kaklamani, Nanjiang Hou, Yiansong Bian, Jennifer Reich, Kenneth Offit, Loren S. Michel, W. S. Rubinstein, Alfred Rademaker, Boris Pasche*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


Purpose: TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR1*6A is a candidate tumor susceptibility allele that has been associated with an increased incidence of various types of cancer. This study was undertaken to analyze all published case-control studies on TGFBR1*6A and cancer and determine whether TGFBR1*6A is associated with cancer. Patients and Methods: All published case-control studies assessing the germline frequency of TGFBR1*6A were included. Studies assessing TGFBR1*6A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed. Results: Overall, TGFBR1*6A carriers have a 26% increased risk of cancer (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.07 to 1.49). Cancer risk for TGFBR1*6A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR1*6A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR1*6A carriers are at increased risk of developing breast cancer (OR, 1.48; 95% CI, 1.11 to 1.96), hematological malignancies (OR, 1.70; 95% CI, 1.13 to 2.54), and ovarian cancer (OR, 1.53; 95% CI, 1.07 to 2.17). Carriers of TGFBR1*6A. who are from the United States are at increased risk of colorectal cancer (OR, 1.38; 95% CI, 1.02 to 1.86). However, Southern European TGFBR1*6A. carriers have no increased colorectal cancer risk. There is no association between TGFBR1*6A and bladder cancer. Conclusion: TGFBR1*6A is emerging as a high-frequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)3236-3243
Number of pages8
JournalJournal of Clinical Oncology
Issue number17
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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