Inherited germline factors found to play bigger role than previously recognized
Two renowned physicians provided information, insight and understanding of cancer prevention and genetic detection/predisposition Nov. 12, 2019 as guests of the La Jolla Community Center’s Distinguished Speakers Series. Epidemiologist Dr. Wael Al-Delaimy and Dr. Scott Lippman, director of Moores Cancer Center at UC San Diego Health, discussed research and outlined what’s in store for genomics testing
Dr. Al-Delaimy presented statistics on the incidence of cancer in the United States and outlined the risk factors in developing certain cancers. According to the National Center for Health Statistics, he told those gathered, cancer is the No. 2 cause of mortality in the country, behind heart disease. Specifically, lung/bronchial cancer is chief — with the highest numbers of cases of cancer deaths among both men and women.
For men, the top diagnosed cancer is prostate cancer; for women, it is breast cancer (in post-menopausal women). The survival rate for lung cancer is sadly 6-9 months, but the incidence is on the decline. And while lung and bronchial cancers are declining overall, for men, the incidence of pancreas and liver cancer is not declining; nor is the incidence of liver and uterine cancer in women.
Dr. Al-Delaimy outlined risk factors in the development of cancer, which include tobacco use (contributing to 35 percent of the causes of cancer), and obesity (contributing to 20 percent of causes of cancers). He also addressed statistics associated with smoking, which he said causes cancer in 50 percent of those who smoke, if they continue, and kills one person every 8 seconds. A smoker, he said, has a 25 fold higher risk in developing lung cancer than non-smokers.
Dr. Lippman outlined the importance of understanding how genomics relate to cancer predictions and familial predispositions to certain cancers.
He addressed the fact that inherited germline factors are being found to play a much bigger role in cancer than previously recognized.
Specifically, Lynch syndrome — a genetic condition associated with a high risk of colorectal, uterine, and other cancers — can be found in roughly 1 in 300 individuals in the U.S., yet only a fraction of people are aware they have it. In spite of this, there is a growing body of research indicating that Lynch syndrome can predispose to a wide spectrum of cancers, many of which can be treated (and, one day, maybe even intercepted) by immune based interventions.
Lippman also discussed the importance of other forms of inherited cancer, such as those caused by inherited mutations in the BRCA1 and BRCA2 genes (associated with high risks of breast, ovarian, pancreatic and prostate cancers), which are likewise present in roughly 1 in 250 U.S. individuals (and 1 in 40 individuals of Ashkenazi Jewish ancestry).
Actress Angelina Jolie has announced she carries an inherited mutation in one of these genes and has undergone risk-reducing surgery, which has been vital to raising awareness of the role of rare variants such as BRCA1 and 2 in cancer predisposition. However, the ways more common germline variants confer cancer risk are less well understood, and being found to play a much bigger role in cancer than previously recognized.
Dr. Lippman further reported that new research on hereditary factors has completely changed how doctors are thinking about certain cancers. One example is pancreatic cancer, which is projected to soon become the second leading cause of cancer-related deaths in the nation. Recent data has shown that as many as 10 percent of pancreatic cancer cases are arising in individuals with specific inherited factors (such as Lynch syndrome or mutations in the BRCA1 or BRCA2 genes), and that many such cancers arise in individuals whose family histories would not have otherwise been flagged as being suspicious for inherited cancer risk.
A positive test can influence precision therapy, Dr. Lippman noted, and has implications for the patient’s family members, through a process known as cascade testing. This has led to national recommendations that all individuals with pancreatic cancer be offered “universal” genetic testing, though such practices will strain an already overburdened workforce of genetic counselors.
As such, Dr. Lippman is leading novel efforts to research methods of delivering cancer genetic medicine (including a new nationwide Stand Up To Cancer study on genetic testing in families affected with pancreatic cancer called the GENERATE study, read more at GENERATEstudy.org) using web-based genetic education as a means of bringing the vital expertise of genetic counselors to individuals who need it the most. For families with such inherited risks to pancreatic cancer, early data are suggesting that there may even be ways to effectively screen individuals for very early signs of cancer, thus bringing some hope to this notoriously lethal diagnosis.
Some good news from his discussion is that as genomic sequencing progresses and the availability of affordable genomic testing becomes available, patients will be more aware of their genetic risks, prevention and earlier treatment options. UC San Diego Health is currently working with the University of California Cancer Centers to look at state-mandated insurance coverage for genetic testing and counseling.
Germline genetic testing and genetic counseling for cancer patients offers California the opportunity to significantly improve overall survival, reduce costs, and improve quality of life for its residents, he concluded.
• For details about La Jolla Community Center’s Distinguished Speakers Series and other Community Center events, visit ljcommunitycenter.org/dss
• Dr. Scott M. Lippman, director of UC San Diego Moores Cancer Center, also reports about the latest in cancer research and prevention in his column “Frontline Cancer,” which appears regularly in La Jolla Light. His column can be read at lajollalight.com/our-columns/frontline-cancer