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TGFBR1*6A and Cancer Risk: A Meta-Analysis of Seven Case-Control Studies

From the Cancer Genetics Program, Division of Hematology/Oncology; the Center for Medical Genetics, Evanston Northwestern Healthcare; and the Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Clinical Genetics Service and the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Boris Pasche, MD, PhD, FACP, Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine, and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 676 N. St Clair St, Suite 880, Chicago, IL 60611; e-mail: b-pasche{at}northwestern.edu.

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.

Related Correspondence

• TGFBR1*6A and Cancer: A Meta-Analysis of 12 Case-Control Studies
  Boris Pasche, Virginia Kaklamani, Nanjiang Hou, Taya Young, Alfred Rademaker, Paolo Peterlongo, Nathan Ellis, Kenneth Offit, Trinidad Caldes, Michael Reiss, and Tongzhang Zheng
  JCO 2004 22: 756-758 [Full Text]
• Association Between TGFBR1*6A and Cancer: Is There Any Evidence?
  Rose Lai
  JCO 2004 22: 2754 [Full Text]

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