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J Clin Oncol. 2003 Sep 1;21(17):3236-43.

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

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  • 1Cancer Genetics Program, Division of Hematology/Oncology, Evanston Northwestern Healthcare, Chicago, IL, USA.

Abstract

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.

Comment in

PMID:
12947057
[PubMed - indexed for MEDLINE]
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