Associations between TCF7L2 polymorphisms and risk of breast cancer among Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study
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The transcription factor 7-like 2 (TCF7L2) gene is part of the Wnt/β-catenin signaling pathway and plays a critical role in cell development and growth regulation. TCF7L2 variants rs12255372 and rs7903146 have been associated with risk of Type 2 diabetes. Few epidemiological studies have examined the association between TCF7L2 and breast cancer risk. We investigated the associations between 25 TCF7L2 single nucleotide polymorphisms (SNPs) and breast cancer in Hispanic and non-Hispanic white (NHW) women from the 4-Corner’s Breast Cancer Study, the San Francisco Bay Area Breast Cancer Study, and the Mexico Breast Cancer Study. A total of 4,703 Hispanic (2,093 cases, 2,610 controls) and 3,031 NHW (1,431 cases, 1,600 controls) women were included. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated using logistic regression to estimate the association between the TCF7L2 SNPs and breast cancer risk. We also examined effect modification by self-reported ethnicity, genetic admixture, and diabetes history. After adjusting for multiple comparisons, four TCF7L2 SNPs were significantly associated with breast cancer overall: rs7903146 (ORTT 1.24; 95 % CI 1.03–1.49), rs3750805 (ORAT/TT 1.15; 95 % CI 1.03–1.28), rs7900150 (ORAA 1.23; 95 % 1.07–1.42), and rs1225404 (ORCC 0.82; 95 % 0.70–0.94). Among women with a history of diabetes, the TT genotype of rs3750804 increased breast cancer risk (OR, 2.46; 95 % CI 1.28–4.73). However, there was no association among women without a diabetes history (OR, 1.06; 95 % CI 0.85–1.32). We did not find significant interactions by ethnicity or by genetic admixture. Findings support an association between TCF7L2 and breast cancer and history of diabetes modifies this association for specific variants.
KeywordsBreast cancer Hispanic Transcription factor 7-like 2 Polymorphisms Type 2 diabetes
The Breast Cancer Health Disparities Study was funded by Grant CA14002 from the National Cancer Institute to Dr. Slattery. The San Francisco Bay Area Breast Cancer Study was supported by grants CA63446 and CA77305 from the National Cancer Institute, grant DAMD17-96-1-6071 from the U.S. Department of Defense and grant 7PB-0068 from the California Breast Cancer Research Program. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000036C awarded to the Cancer Prevention Institute of California; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. The 4-Corner’s Breast Cancer Study was funded by grants CA078682, CA078762, CA078552, and CA078802 from the National Cancer Institute. The research also was supported by the Utah Cancer Registry, which is funded by Contract N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute or endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors. The Mexico Breast Cancer Study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002-C01-7462). We would also like to acknowledge the contributions of the following individuals to the study: Sandra Edwards for data harmonization oversight, Erica Wolff and Michael Hoffman for laboratory support, Carolyn Ortega for her assistance with data management for the Mexico Breast Cancer Study, Jocelyn Koo for data management for the San Francisco Bay Area Breast Cancer Study, Dr. Tim Byers for his contribution to the 4-Corner’s Breast Cancer Study, Dr. Josh Galanter for assistance in selection of AIMs markers for the study, Dr. Elad Ziv for his input into the study, and Drs. Sue Ingles and Wei Wang for their contribution to the study.
Conflicts of interest
The authors declare that they have no conflict of interest.
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