Germline ATBF1 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 (3381del)) 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 3381del 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 3381del allele may influence prostate cancer susceptibility.
Xu
Junyan
J
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Sauvageot
Jurga
J
Ewing
Charles M
CM
Sun
Jielin
J
Liu
Wennuan
W
Isaacs
Sarah D
SD
Wiley
Kathleen E
KE
Diaz
Lina
L
Zheng
S Lilly
SL
Walsh
Patrick C
PC
Isaacs
William B
WB
D000483:Alleles; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis / Q000097:blood / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D012307:Risk Factors
D003062:Codon; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C071660:ZFHX3 protein, human