title: Analysis of genetic variants of the poly(ADP-ribose) polymerase-1 gene in breast cancer in French patients.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Cao
authors.forename: Xiaogan
authors.initials: X
authors.lastname: Wang
authors.forename: Lucien
authors.initials: L
authors.lastname: Frappart
authors.forename: Dominique
authors.initials: D
authors.lastname: Rigal
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Tong
mesh_terms: 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
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases