Rare variants, combined with background genetic risk factors, may account for many unexplained cases of familial breast cancer, and knowing the specific genes involved could inform choice of prevention and treatment strategies, according to findings presented on October 20, 2017 in a plenary session at the American Society of Human Genetics (ASHG) 2017 Annual Meeting in Orlando, Florida. Researchers Na Li, MD, who presented the work; Ian Campbell, PhD, lead investigator; and their colleagues at the Peter MacCallum Cancer Centre in Melbourne, Australia, focused their study on patients at high risk of breast cancer: those with a personal or family history who were seeking an explanation. “When you know which gene is conferring the risk of breast cancer, you can provide a more precise estimate of risk, know what to expect and watch out for, and tailor risk management strategies to the patient,” said Dr. Campbell. Unfortunately, in about half of these high-risk patients, no known genetic cause was found, suggesting a more complicated explanation. In such cases, cancer geneticists had long suspected that polygenic risk (risk conferred by a combination of genetic variants) was involved. Genes do not work on their own, but rather as part of one’s overall genetic context, explained Dr. Li. “That ‘polygenic risk’ background is like a landscape full of hills and valleys, with each risky variant like a house on top of it,” she said. “If you inherit a high-risk variant – a tall house – but live in a valley, your overall risk of breast cancer may end up being average because your genetic landscape pulls it down.”Login Or Register To Read Full Story