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

PURPOSE

TGFBR16A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR16A 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 TGFBR16A and cancer and determine whether TGFBR16A is associated with cancer.

PATIENTS AND METHODS

All published case-control studies assessing the germline frequency of TGFBR16A were included. Studies assessing TGFBR16A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed.

RESULTS

Overall, TGFBR16A 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 TGFBR16A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR16A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR16A 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 TGFBR16A 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 TGFBR16A 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.