c‐MYC Asn11Ser is associated with increased risk for familial breast cancer

c‐MYC is a multifaceted protein that regulates cell proliferation, differentiation and apoptosis. Its crucial role in diverse cancers has been demonstrated in several studies. Here, we analysed the influence of the rare c‐MYC Asn11Ser polymorphism on familial breast cancer risk by performing a case‐control study with a Polish (cases n = 349; controls n = 441) and a German (cases n = 356; controls n = 655) study population. All cases have been tested negative for mutations in the BRCA1 and BRCA2 genes. A joint analysis of the Polish and the German study population revealed a 54% increased risk for breast cancer associated with the heterozygous Asn11Ser variant (OR = 1.54, 95% CI 1.05–2.26, p = 0.028). The breast cancer risk associated with this genotype increases above the age of 50 years (OR = 2.24, 95% CI 1.20–4.21, p = 0.012). The wild‐type amino acid Asn of this polymorphism is located in the N‐terminal MYC transactivation domain and is highly conserved not only among most diverse species but also in the N‐MYC homologue. Due to the pivotal role of c‐MYC in diverse tumours, this variant might affect the genetic susceptibility of other cancers as well. © 2005 Wiley‐Liss, Inc.