Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: a case-control study

• Main Authors: Schmutzler Rita K, Meindl Alfons, Hemminki Kari, Shanmugam Kalai S, Burwinkel Barbara, Sutter Christian, Wappenschmidt Barbara, Kiechle Marion, Bartram Claus R, Frank Bernd
• Format: Article
• Language: English
• Published: BMC 2006-11-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/6/268
• ISSN: 1471-2407

<p>Abstract</p> <p>Background</p> <p>The transcription factor 7-like 2 (TCF7L2) is a critical component of the Wnt/β-catenin pathway. Aberrant <it>TCF7L2 </it>expression modifies Wnt signaling and mediates oncogenic effects through the upregulation of <it>c-MYC </it>and <it>cyclin D</it>. Genetic alterations in <it>TCF7L2 </it>may therefore affect cancer risk. Recently, <it>TCF7L2 </it>variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes.</p> <p>Methods</p> <p>We investigated the effect of the <it>TCF7L2 </it>rs12255372 variant on familial breast cancer (BC) risk by means of TaqMan allelic discrimination, analyzing <it>BRCA1/2 </it>mutation-negative index patients of 592 German BC families and 735 control individuals.</p> <p>Results</p> <p>The T allele of rs12255372 showed an association with borderline significance (OR = 1.19, 95% C.I. = 1.01-1.42, <it>P </it>= 0.04), and the Cochran-Armitage test for trend revealed an allele dose-dependent association of rs12255372 with BC risk (<it>P</it>_trend= 0.04).</p> <p>Conclusion</p> <p>Our results suggest a possible influence of <it>TCF7L2 </it>rs12255372 on the risk of familial BC.</p>