Journal of Clinical Oncology, Vol 22, No 4 (February 15), 2004: pp. 756-758
© 2004 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2004.99.271
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,
Tongzhang Zheng
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
Memorial Sloan-Kettering Cancer Center, New York, NY
Hospital Clínico San Carlos, Martin Lagos, Madrid, Spain
Robert Wood Johnson Medical School, New Brunswick, NJ
Yale University School of Epidemiology and Public Health, New Haven, CT
To the Editor:
Following the publication of our meta-analysis on TGFBR1*6A and cancer [1], several colleagues have shared with us the results of their own unpublished case-control studies. We are now reporting all the data made available to us as of November 2003—a total of 12 case-control studies that included 3,451 controls and 4,399 cases (Table 1). The additional data come from several sources: (1) Dr Michael Reiss from the Cancer Institute of New Jersey genotyped 98 women with sporadic breast cancer and 91 age-matched healthy women from New Haven County in Connecticut. Ninety-one percent of the women were white, 7% were African American, and 2% were of other racial/ethnic groups. Blood samples were collected as part of a parent case-control study to assess the relationship between serum organochlorines and breast cancer risk. (2) Dr Nathan Ellis from Memorial Sloan-Kettering Cancer Center genotyped 767 sporadic colon cancer cases and 767 matched controls from New York, NY. All cases and controls were Ashkenazi Jews. Cases were collected as a consecutive series at Memorial Sloan-Kettering Cancer Center, and controls were obtained from the New York Cancer Project. (3) Dr Trinidad Caldes genotyped 237 cases of sporadic colorectal cancer, 275 cases of sporadic breast cancer, and 294 controls from Madrid, Spain. Cases and controls had the same mean age and were all residents of Madrid. (4) Dr Kenneth Offit provided DNA samples from 463 breast cancer cases and 330 healthy controls from New York City, of similar age and ethnic background. The samples were genotyped in Dr Pasche's laboratory at the Northwestern Cancer Genetics Program. (5) We have also included the Northwestern Cancer Genetics Program unpublished data from Chicago, IL, which includes 121 consecutive cases of breast, colon, and ovarian cancer, and 123 controls of similar ethnic background. Combined analysis of the 12 studies shows that TGFBR1*6A allelic frequency among cases (0.090) is 27% higher than among controls (0.071; P = .0005). TGFBR1*6A carriers have a 24% increased risk of cancer (odds ratio, 1.24; 95% CI, 1.10 to 1.40), which is almost identical to the 26% increased risk found previously [1]. As in our previous report, the overall cancer risk is significantly increased for both TGFBR1*6A heterozygotes (19%) and homozygotes (70%; Table 2 ). TGFBR1*6A carriers have a 38% increased risk of breast cancer and a 41% increased risk of ovarian cancer, which are similar to our previous risk estimates. The only notable difference of this study as compared with the previous study is the new evidence that TGFBR1*6A carriers have a 20% increased risk of colorectal cancer (Table 3).
Inclusion of these additional studies addresses the crucial issue of publication bias discussed in our recent communication [1]. Overall, only three of the 12 case control studies reported here showed an association between TGFBR1*6A and cancer. This strongly argues against a publication bias. The results of this second meta-analysis that included 7,850 individuals reinforce our previous findings and confirm TGFBR1*6A as the most common tumor susceptibility allele reported to date that increases the risk of breast, ovarian, and colorectal cancer.
Authors' Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
Acknowledgment
This work was supported in part by grants CA89018 and CA90386 (B.P.) from the National Cancer Institute (Bethesda, MD) and a gift from the Mander Foundation (Chicago, IL). Dr Pasche is the recipient of a Career Development Award from the Avon Foundation, New York, NY.
REFERENCE
1. Kaklamani V, Hou N, Bian Y, et al: TGFBR1*6A and cancer risk: A metaanalysis of seven case-control studies. J Clin Oncol 21:3236-3243, 2003[Abstract/Free Full Text]
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