The
poly(ADP-ribose) polymerase (PARP/
ADPRT)
protein family catalyzes the synthesis of cellular
poly(ADP-ribose) following DNA damage and is involved in genomic integrity by regulating cellular responses to DNA damage and apoptosis. Moreover,
ADPRT inhibition contributes to a protective effect against
cancer development. These findings render
ADPRT an attractive candidate susceptibility gene for
breast cancer, and thus the goal of this study was to evaluate the possible involvement of
ADPRT sequence variations in
breast cancer susceptibility. The complete sequence of the 23 exons and flanking intronic sequences of the
ADPRT gene was analyzed in 54 affected individuals from distinct high-risk non-BRCA1/2 French Canadian families. No deleterious truncating mutation was identified in the coding region. However, 34 sequence variations were identified, among which seven are coding variants and seven are novel changes. All coding variants and intronic changes located in the vicinity of the coding variants identified in the case series were also analyzed in a cohort of 73 unrelated healthy French Canadian individuals. Interestingly, one missense variant (Pro377Ser) was observed in three different
breast cancer cases but was not present among unaffected individuals. We have conducted here an exhaustive detailed mutation and haplotype tagging analysis of the
ADPRT gene with regard to
breast cancer, providing useful data for other large-scale association studies. Additional studies in other cohorts and other populations are however needed to further evaluate the implication of the Pro377Ser missense variant with regard to
breast cancer susceptibility.