Analysis of genetic variants of the poly(ADP-ribose) polymerase-1 gene in breast cancer in French patients.
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that catalyzes the poly(ADP-ribosyl)ation of target proteins in response to DNA damage and has been proposed to play a role in DNA repair, recombination, transcription, cell death, cell proliferation, as well as in stabilization of the genome. We have recently shown that PARP-1 deficiency causes mammary tumorigenesis in mice. In the present study, we investigated whether genetic variants and single nucleotide polymorphisms (SNPs) of PARP-1 contribute to human breast cancer. To this end, we screened all PARP-1 exons, 7.1kb of intron-exon junction and 1.0-kb promoter sequences in 83 French patients with breast cancer and 100 controls by direct sequencing of genomic DNA. Twenty rare genetic variants of PARP-1, including c.1148C>A (Ser383Tyr), c.1354C>A (Arg452Arg), c.2819A>G (Lys940Arg) were detected in nine (10.8%) breast cancers of these patients. Among 31 polymorphic sites examined, five haplotype-tagging SNPs (htSNPs) of PARP-1 were identified. Interestingly, the genotype distribution of htSNP c.852T>C (Ala284Ala) was likely associated with loss of estrogen- and progesterone-receptor expression. The present study implies that genetic variants of PARP-1 may contribute to breast cancerogenesis and that PARP-1 htSNP c.852T>C (Ala284Ala) may influence hormonal therapy of breast cancer.
Cao
Wen-Hui
WH
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 5, Dong Dan San Tiao, Beijing 100005, China.
Wang
Xiaogan
X
Frappart
Lucien
L
Rigal
Dominique
D
Wang
Zhao-Qi
ZQ
Shen
Yan
Y
Tong
Wei-Min
WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D044584:Carcinoma, Ductal / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases