Abstract CN04-04: Cancer predisposition: I say genetics, you say genomics, but are we there yet?
Authors: Eng Charis 
Published: May 2012

In the United States, major contributors to premature mortality are behavior (40%) and genetics (35%). Amongst all diseases, scientific knowledge regarding genetic predisposition to cancer is one of the most advanced. Based on multidisciplinary research spanning the last 2 deacdes, the practice of clinical cancer genetics has empowered patients, their family members and healthcare providers with genetics-informed cancer risk assessment and management. On average, 10% of all cancers are caused by a strong (high penetrance) genetic predisposition, with a range between 5% and 30%. Yet, are those at genetic risk for cancer reaching proper care for prevention? An interactive-electronic family cancer history survey performed in a cancer hospital serving the population of central Ohio revealed that only 7% of all those assessed by cancer genetics professionals to be at high risk for cancer predisposition were recognized either by the patients' healthcare providers or the patients themselves, and referred to cancer genetics professionals. A recent national survey of &gt;35,000 women without personal breast or ovarian cancer histories revealed that ∼1% (∼350) were at high risk for breast and/or ovarian cancer based on family history alone (i.e., at risk for carrying BRCA1/2 mutation). Yet, of these ∼350, only 10% (∼35) discussed this genetic risk with any healthcare provider, and only ∼1.5% (∼4) had BRCA1/2 gene testing. BRCA1/2 are “the most popular”” breast cancer predisposition genes and yet this population is under-serviced. There are at least 6 other high penetrance breast cancer-predisposition genes, including PTEN. Because of the lack of a systematic manner of identifying and managing all individuals at genetic risk for cancer, the great majority of individuals at high risk for cancer predisposition are never identified (in this BRCA1/2 national survey, 90%) nor reach appropriate medical care (99%). Therefore, we believe that individuals and their families at genetic risk for cancer are an under-served population.

Paradoxically or perhaps due to the lack of knowledge of the availability and the power of validated genetics services, direct-to-consumer (DTC) personal genome scanning or screening has begun to gain popularity or at least peak public interest. In contrast to validated genetic testing, that is always focused on one or very few genes guided by medical and family histories, personal genomic scanning is currently based on multiple statistical comparisons called genome-wide association. Validated genetic testing is offered by healthcare providers to individuals at high risk of Mendelian genetic disease. This model of validated Mendelian genetic testing focuses only on one or a few genes that are known to be strongly associated with disease. If a gene mutation is identified, the individual is at high risk (sometime ∼100% likelihood) of developing the associated disease, and this type of genetic knowledge is clinically utile and actionable for prevention or very early detection. A few examples include Lynch syndrome, hereditary breast-ovarian cancer syndrome and Cowden syndrome.

Personal genomic screening, or personal genome testing or profiling, uses data derived from genome-wide association studies to predict an individual's probability of developing many different disorders and traits in a lifetime. The majority of such genome-wide association studies are case-control studies which study hundreds to thousands of individuals to search for genetic markers shown to be statistically more common in individuals with disease compared with controls. These genetic markers are most commonly Single Nucleotide Polymorphisms (SNPs). They are common in the general population and may or may not have a known functional consequence. These types of data usually provide an odds ratio or relative risk of the likelihood that an individual with a particular genotype will have disease. As a result, most such DTC scanning currently has no to little analytic validity (because SNP choice and algorithms may differ), no clinical validity, no clinical utility and no actionability. Thus, interdisciplinary research directed at clinical outcomes or subsets of individuals or clinical situations where they can be used in a valid and actionable way should be performed.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN04-04.