What explains breast cancer familial aggregation?

Dr Shuai Li presents genetic models that explain the residual breast cancer familial aggregation and relevant implications for breast cancer genetic susceptibility and risk prediction.

DR SHUAI LI
Victorian Cancer Agency Early Career Research Fellow / Senior Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health 
University of Melbourne 

Rare pathogenic variants in known breast cancer susceptibility genes and known common susceptibility variants do not fully explain the familial aggregation of breast cancer. We studied 17,425 population-based families with gene-panel sequencing data to investigate the genetic models that explain the residual familial aggregation. After considering known susceptibility genes, the residual familial aggregation is best explained by common, high-penetrant recessively inherited genes and a polygenic component that represents the effects of a large number of variants each associated with a small increment in risk. The proportion of the residual familial variance explained by the recessively inherited genes was 40% at age 20-29 years and decreased with age thereafter. The model predicted age-specific familial relative risks consistent with those observed by large epidemiological studies. The findings have implications for strategies to identify new breast cancer susceptibility genes and improve disease risk prediction, especially at a young age.

Dr Shuai Li is a Victorian Cancer Agency Early Career Research Fellow and Senior Research Fellow at the Centre for Epidemiology and Biostatistics, University of Melbourne. Dr Li is a medically trained epidemiologist, with research interests in genetic and epigenetic epidemiology, twin and family research, and cancer risk modelling.

Dr Li obtained his PhD at the University of Melbourne in 2018, followed by a postdoc at Cambridge University. He has won research funding of >$8 million from such as NHMRC, Cancer Australia and the Cure Cancer Foundation, including a Cancer Council Victoia Postdoctoral Research Fellowship (2018-2019) and a Victorian Cancer Agency Early Career Research Fellowship (2020-2022). His works have been recognised by multiple research excellence awards, including the 2020 Runner-up for the Victorian Premier's Awards for Health and Medical Research and the 2018 Victorian Comprehensive Cancer Centre Picchi Award for Excellence in Cancer Research.