Germline ATBFI mutations and prostate cancer risk

BACKGROUND. ATBF1 has been recently identified as a candidate prostate tumor suppressor gene. In addition to more unique mutations, two somatic mutations (shortening of a polypyrimidine tract [Poly(T)_n] and a deletion beginning at codon 3381 (3381 del)) were each observed in multiple prostate cancer samples and both appear to have an impact on ATBF1 gene function and expression. METHODS. We assayed two recurrent sequence variants in germline DNA from prostate cancer cases and controls, and examined whether carriers of these variants are at increased risk for prostate cancer. RESULTS. We found Poly(T)_n variants in both normal and matched tumor DNA samples from multiple patients, indicating a germline origin in each case. Genotyping germline DNA samples indicated that 3381 del was significantly associated with prostate cancer risk among sporadic cases (P = 0.03), but not among men with hereditary disease. CONCLUSIONS. Our study indicates that the germline 3381 del allele may influence prostate cancer susceptibility.