Cellular and molecular mechanisms of breast cancer susceptibility

Abstract

There is a plethora of recognized risk factors for breast cancer (BC) with poorly understood or speculative biological mechanisms. The lack of prevention options highlights the importance of understanding the mechanistic basis of cancer susceptibility and finding new targets for breast cancer prevention. Until now, we have understood risk and cancer susceptibility primarily through the application of epidemiology and assessing outcomes in large human cohorts. Relative risks are assigned to various human behaviors and conditions, but in general the associations are weak and there is little understanding of mechanism. Aging is by far the greatest risk factor for BC, and there are specific forms of inherited genetic risk that are well-understood to cause BC. We propose that bringing focus to the biology underlying these forms of risk will illuminate biological mechanisms of BC susceptibility.

ELF5: A Molecular Clock for Breast Aging and Cancer Susceptibility

“…High-risk women who are carriers of inherited germline mutations in genes such as BRCA1, BRCA2, and PALB2 face a potentially seven-fold higher risk than those who are at average risk [4]. Although factors like parity, obesity, smoking, and alcohol consumption have been identified as additional risk factors, their increased risk is smaller than that associated with inherited germline mutations and aging [5,6]. Thus, germline mutations and aging are the predominant risk factors for BC.…”