POLY(ADP-RIBOSE) POLYMERASE IN HUMAN BREAST-CANCER - A CASE-CONTROL ANALYSIS

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribo se) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP en zyme activities in the development of human breast cancer were evaluat ed in a cancer case-control study. A total of 309 Caucasian women (gre ater than or equal to 50 years old) were evaluated for the PARP genoty pe, 70 of whom had histologically confirmed breast cancer, 128 women w ith benign breast diseases as study controls, and 111 reference contro ls. Age was significantly associated with case-control status (p < 0.0 001), but family history of breast cancer, age at menarche, age at fir st 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 PARP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-ad justed odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for t he below-median oligonucleotide-induced PARP was suggestive of an asso ciation, In subjects with the AB or BE genotype, the mean H2O2-induced PARP enzyme activity 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 polymorphis m of the PARP pseudogene on chromosome 13 is not associated with the d evelopment of breast cancer in our study population; (b) oligonucleoti de-induced PARP activity may 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 enzym e activation.