TP53-binding protein variants and breast cancer risk: a case-control study

Allelic discrimination was performed to investigate the frequencies of 53BP1 D353E, G412S, and K1136Q and of 1347_1352delTATCCC in 353 patients with breast cancer and 960 control individuals.No significant association of 53BP1 D353E, G412S, or K1136Q with breast cancer risk was detected. 53BP1 1347_1352delTATCCC, leading to the loss of an isoleucine and a proline residue, showed a nonsignificant inverse association with breast cancer risk (odds ratio = 0.61, 95% confidence interval = 0.22 to 1.68, P = 0.34).The lack of association casts doubt on the putative effects of D353E, G412S, and K1136Q on breast cancer risk. Investigating a larger study cohort might elucidate the influence of the 6bp deletion 1347_1352delTATCCC. Studying the functional effect and the impact of this variant on the risk of other cancers may be revealing.The TP53-binding protein (53BP1), a conserved nuclear protein, was initially identified to interact with the DNA-binding domain of TP53, thus enhancing TP53-mediated transcriptional activation [1,2]. In response to exogenous exposure to ionising radiation, 53BP1 becomes hyperphosphorylated and rapidly localises to sites of DNA double-strand breaks, demonstrating its determining role in DNA damage signalling [3,4]. 53BP1-deficient mice exhibit growth retardation, high radiation sensitivity, and tumour development – features that are indicative of a defective DNA damage response [5]. 53BP1 is involved in the phosphorylation of various ataxia telangiectasia mutated protein (ATM) substrates such as cell cycle checkpoint kinase 2 (CHEK2) [3,6]. Mutations in ATM, CKEK2, and its substrate, TP53, have been shown to predispose to cancer [6-9]. Therefore, we selected 53BP1 as an attractive candidate gene for breast cancer susceptibility.This is the first study to investigate the effects of the 53BP1 single nucleotide polymorphisms (SNPs) D353E (1059C>G), G412S (1234G>A), and K1136Q (3406A>C) on breast cancer risk, analysing 353 German patients with breas