A positive result essentially means a harmful mutation was detected in a gene that increases the risk for cancer . Unfortunately , this field of medicine has quite a bit of ambiguity – negative test results can mean a couple of things . It can mean that either it isn ’ t a hereditary cancer condition , or there hasn ’ t been a gene change found yet . While they can ’ t rule anything out , it does make a cancer risk less likely . The third possible test result is VUS ( variant of uncertain significance ), which means that a change was found , but it is unclear whether that is a harmful change or not . In these cases , the companies follow the patient on an ongoing basis and reassess on a regular timeline and let the physician know if they receive updated information . About 90 % of the time , these come back as negative . Even with negative results , there can still be an increased risk of cancer based on family history and they will make recommendations accordingly . For example , if a patient is diagnosed with colon cancer at age 50 and no underlying gene problem is found , they still recommend family members start colonoscopies at age 40 . As a general rule , they suggest screening 10 years before the youngest age of diagnosis .
As mentioned previously , most cancers are sporadic . Hereditary cancer accounts for just about 5-10 % of overall cases . There is a third category known as familial cancer , when multiple family members have the same type of cancer , and while there is no particular gene being impacted , clearly it is running in that family . It tracks more like heart disease or diabetes . This could be caused by multiple genes or a combination of genes and environment .
There are two types of hereditary colon cancer : familial adenomatous polyposis ( FAP ) syndrome and Lynch syndrome ( also known as hereditary non-polyposis colorectal cancer syndrome , or HNPCC ). FAP was first described as a condition in 1847 , but it wasn ’ t until 1991 that the underlying gene was actually found . Lynch syndrome was first described in 1967 , with the first genes identified in 1993 .
With Lynch syndrome , the Amsterdam criteria used to help identify those at risk were developed in 1990 and revised to Amsterdam II criteria in 1999 using the “ 3-2-1 Rule .” They look for at least 3 relatives ( at least one of them being a first-degree relative of the other two ), across at least 2 generations , and at least 1 diagnosed before age 50 . The Amsterdam II expansion included other HNPCC-associated cancers ( endometrium , small bowel , ureter , renal and pelvic ). In 1997 , the Bethesda criteria were established ( revised in 2004 ) to determine who should undergo microsatellite instability testing . The initial criteria focused on younger patients , often around age 40 , and included colorectal adenomas ; the revised criteria included multiple primary cancers .
First identified in the 1990s , microsatellite instability ( MSI ) looks at tumor DNA to determine how stable it is ; high MSI is found to be associated with Lynch syndrome . Currently , there is a universal screening recommendation that all colon and uterine cancers should have MSI testing , but it is also used in other types .
Hereditary breast and ovarian cancer ( HBOC ) was found more recently in the late 80s . Geneticist Mary-Claire King , PhD , working at Berkeley , found the BRCA1 gene in 1994 , then the BRCA2 gene in 1995 . They now run a test panel to scan multiple genes at the same time , looking at sequencing as well as deletion duplication .
The most common hereditary cancers include : » Breast – 5-10 % ( approx . 20 genes ) » Ovarian – 10 % ( approx . 12 genes ) » Uterine – 5-10 % ( approx . 6 genes ) » Colon – 5-10 % ( approx . 20 genes ) » Prostate – 5-10 % ( approx . 14 genes ) » Pancreatic – 10 % ( approx . 13 genes )
Other hereditary cancers include melanoma , renal , paragangliomas and pheochromocytomas , and brain tumors . Another area that has expanded in recent years is hereditary pediatric cancers . These are more challenging from a referral standpoint , as some associated conditions are syndromic , needing evaluation by a pediatric geneticist .
Recent advancements include the ability to analyze RNA in addition to DNA , a universal MSI for colon and uterine cancers and expanded MSI for other tumor types , next-generation sequencing on tumors in addition to germline samples , and liquid biopsies .
In this ever-changing field , the focus is always on the risks and recommendations for patients and their families based on new technological developments . Dr . Goodin and her colleagues use the National Comprehensive Cancer Network to guide their treatment plans , and look forward to all of the advancements on the horizon for years to come .
This is a summary of the Senior Physicians Speaker Series presentation . For a link to view the full presentation , please email foundation @ glms . org .
Kathryn Vance is the Communications and Event Coordinator at the Greater Louisville Medical Society .
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