Short CommunicationIntron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 yearsWang-Gohrke, Shana; Becher, Heikob; Kreienberg, Rolfa; Runnebaum, Ingo B.a*; Chang-Claude, Jennyc Author Information aDepartment of Obstetrics and Gynaecology, Molecular Biology Laboratory, University of Ulm, Ulm, bDepartment of Tropical Hygiene and Public Health, University of Heidelberg, Heidelberg and cDivision of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany. Sponsorship: The epidemiologic case–control study was supported by the Deutsche Krebshilfe (Project number 70492). The molecular biology study was funded by the Deutsche Forschungsgemeinschaft (DFG RU476/2) and the Medical Faculty of the University of Ulm (P.589 and P.685). Correspondence to Dr Jenny Chang-Claude, Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Postfach 101949, 69009 Heidelberg, Germany Tel: +49 622 142 2373; fax: +49 6221 422 203; e-mail: [email protected] Received 15 August 2001 Accepted 25 October 2001 *Current address: Department of Obstetrics and Gynaecology, University of Freiburg, Freiburg, Germany. Pharmacogenetics: April 2002 - Volume 12 - Issue 3 - p 269-272 Buy Abstract We used a large population-based case–control study to determine whether three known p53 polymorphisms, intron 3 16 bp duplication, codon 72Arg/Pro and intron 6 Msp I restriction fragment length polymorphism, alter the risk for breast cancer in German women. For all three polymorphisms, the odds ratios (ORs) for breast cancer were increased in women carrying the rare allele; however, this was statistically significant only for the 16 bp duplication polymorphism. Compared with the 16 bp duplication wild-type A1/A1 genotype, ORs for A1/A2 genotype and A2/A2 genotype were 1.3 [95% confidence interval (CI) 1.0–1.7] and 1.7 (95% CI 0.8–3.4), suggesting an allele dosage effect (trend test, P = 0.03). Significant evidence was found for a differential effect by family history of breast cancer (P = 0.03 for interaction), with the OR being 5.3 among women with a first degree family history. Our data suggest that inheritance of an intronic polymorphism in the p53 gene increases breast cancer risk appreciably in women by the age of 50 years with a family history of breast cancer in the German population. © 2002 Lippincott Williams & Wilkins, Inc.