Poly(ADP-ribose) polymerase in human breast cancer: A case-control analysis

Jennifer J. Hu, George C. Roush, Neil Dubin, Marianne Berwick, Daniel F. Roses, Matthew N. Harris

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribose) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP enzyme activities in the development of human breast cancer were evaluated in a cancer case-control study. A total of 309 Caucasian women (≤ 50 years old) were evaluated for the PARP genotype, 70 of whom had histologically confirmed breast cancer, 128 women with benign breast diseases as study controls, and 111 reference controls. Age was significantly associated with case-control status (p < 0.0001), but family history of breast cancer, age at menarche, age at first live birth and parity were not. The frequency of the PARP B allelle was similar in breast cancer cases (0.14), study controls (0.13), and reference controls (0.15). In a subset of 14 breast cancer cases and 32 study controls, the mean PRAP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-adjusted odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for the below-median oligonucleotide-induced PARP was suggestive of an association. In subjects with the AB or BB genotype, the mean H2O2-induced PARP enzyme nctivity was significantly higher (p = 0.02, adjusted for case-control status and age) compared with that in subjects with the AA genotype, These findings indicate that: (a) the genetic polymorphism of the PARP pseudogene on chromosome 13 is not associated with the development of breast cancer in our study population; (b) oligonucleotide-induced PARP activity mag be useful for identifying postmenopausal women at increased risk for breast cancer; and (c) there is a possible functional link between the genotype of the PARP pseudogene and enzyme activation.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalPharmacogenetics
Volume7
Issue number4
DOIs
StatePublished - Sep 6 1997
Externally publishedYes

Keywords

  • Human breast
  • Poly(ADP-ribose) polymerase
  • Polymorphism

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Poly(ADP-ribose) polymerase in human breast cancer: A case-control analysis'. Together they form a unique fingerprint.

  • Cite this