Differential association of BRCA1 and BRCA2 genes with some breast cancer-associated genes in early and late onset breast tumors

Background: Accumulating evidence indicating more aggressive features of breast carcinoma (BC) in young women than their older counterparts have raised the question of whether these differences are present at the genetic level. Methods: For this purpose, we performed a comparative analysis of the frequency of deletions of BRCA1, BRCA2, BRCAX, TP53, ATM, and RB1 and amplification of Cyclin D1 and also studied the interrelation and prognostic significance of these genetic alterations in 30 early onset (less than or equal to40 years) and 33 late onset (>40 years) cases of BC. These gene alterations were also studied in 11 other types of breast lesions. Results: A differential pattern of alterations (deletion/amplification) was observed in the two age groups, with the sequence in younger women being BRCA1 (72%), TP53 (71%), ATM (64%), BRCA2 (62%), RB1 (60%), Cyclin D1 (43%), and BRCAX (24%) and that in the older group being TP53 (66%), RB1 (63%), BRCA1 (56%), ATM (53%), BRCA2 (45%), Cyclin D1 (24%), and BRCAX (23%). Similar, differential correlations were also seen with several clinicopathological parameters, prognosis, and combinations of alterations among these genes in the two age groups. Conclusions: Differential frequencies and interrelationships of genetic alterations and prognoses in these two age groups indicate that the molecular pathways for the development of tumors in both age groups may not be similar, though the ultimate effect is deregulation of cell cycle checkpoints and defects in the DNA repair pathway.