Your browser version may not work well with NCBI's Web applications. More information here...
1: J Clin Oncol. 2003 Sep 1;21(17):3236-43.Click here to read Links
Comment in:
J Clin Oncol. 2004 Jul 1;22(13):2754; author reply 2754-5.
J Clin Oncol. 2005 Oct 20;23(30):7743-4; author reply 7744-6.

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

Kaklamani VG, Hou N, Bian Y, Reich J, Offit K, Michel LS, Rubinstein WS, Rademaker A, Pasche B.

Cancer Genetics Program, Division of Hematology/Oncology, Evanston Northwestern Healthcare, Chicago, IL, USA.

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 highfrequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.

PMID: 12947057 [PubMed - indexed for MEDLINE]