HealthCare Providers

Prevention and early detection
While most cancers arise from genetic mutations acquired during a person’s lifetime, approximately 5-10% of all cancers are first triggered due to the presence of an inherited variant. Individuals with inherited cancer syndromes have an increased risk to develop cancer, often at a younger age, and also have a higher likelihood to develop more than one cancer in their lifetime. Additionally, their siblings, children, and other family members may be at risk to have the same variant. With the advent of genetic screening, it is possible to analyze a person’s DNA and determine whether they have an inherited mutation putting them at a higher risk to develop cancer. With this information, individuals can take action earlier to prevent or identify cancer at its earliest stages when it is most curable.

No Cost
There is no cost to participate in the HOP genetic screening study for inherited cancer syndromes. Participants read about the benefits and risks of participating in the Healthy Oregon Project and consent to participate using a secure, HIPAA compliant mobile HOP App.

Genetic screening, analysis, reporting of results are covered by this study (including genetic counseling for anyone with a positive result).

Although most insurance companies may cover the costs of the recommended preventive measures based on having a familial gene variant, preventive care may not be covered in full. There may be out-of-pocket costs due to patient’s deductible or copayment amount. A patient should first verify their insurance coverage before undergoing any medically recommended preventive measures.

If your patient does not have health insurance, the Participant Navigator can assist with insurance enrollment or accessing financial assistance services available in most clinics and health systems.

Positive and Negative Results Provided
Results are provided to all participants who choose this option and are ready in about six months. These reports are made available in the HOP participants HIPAA compliant Healthy Oregon Project app.

• HOP screens 32 genes associated with inherited cancer syndromes and familial hypercholesterolemia in a clinically certified CLIA laboratory at OHSU. The test is similar to but not quite as complete as testing performed by major commercial genetic testing firms. This screening test is not meant to replace clinical testing for high risk individuals, and will not detect approximately 10% of medically relevant inherited cancer risk in the genes analyzed.
• When a likely pathogenic or pathogenic variant is present in these genes, the individual’s risk for cancer is likely increased over the general population. The degree of increased risk and type(s) of cancer varies between genes and variant.

The most common inherited cancer syndromes that are being screened for are:

• Hereditary Breast and Ovarian Cancer (HBOC) 
  Families with HBOC have an increased risk for breast, ovarian, prostate, and pancreatic cancers. The genes associated with HBOC are BRCA1 and BRCA2.
  More about HBOC
  Hereditary breast and ovarian cancer syndrome (HBOC), predisposes women to very high risks of breast and ovarian cancer. HBOC is caused by variants in two genes, BRCA1 and BRCA2. Variants in these genes are also associated with substantially increased risks of other cancers. These genes are all involved in a specific DNA repair pathway. Effective interventions for HBOC exist. Specific recommendations on treatments and likely clinical outcomes are dependent upon the individual, the family history of cancer, and the specific variant present in these genes.
• Lynch Syndrome 
  Families with Lynch syndrome have an increased risk for colorectal, uterine, stomach, and ovarian cancers. The genes associated with Lynch syndrome are MLH1, MSH2, EPCAM, MSH6, and PMS2.
  More about Lynch Syndrome
  Lynch syndrome is caused by variants in a different set of DNA repair pathway genes. The complex biology of variants in these genes is associated with a significant risk of many types of tumors, principally, colorectal and endometrial. As with HBOC, effective interventions exist and specific recommendations on treatments and outcomes are dependent on individual, family, and specific variant.
• Familial Adenomatous Polyposis (FAP) and Attenuated FAP (AFAP)
  Families with FAP or AFAP have an increased risk for colorectal polyps and colorectal cancer, as well as small bowel, pancreatic and thyroid cancers. FAP and AFAP are caused by pathogenic variants in the APC gene.
• CHEK2
  Families with pathogenic CHEK2 variants have increased risks for breast cancer, colon cancer, and possibly other cancers. CHEK2 is responsible for sensing DNA damage, and is considered a moderate risk breast cancer gene, meaning individuals with CHEK2 variants have an increased for breast cancer over the general population, but not as high as individuals with a variant in a high-risk breast cancer gene (i.e., BRCA1). There are two relatively common CHEK2 variants (found in about 1% of Caucasians) associated with about a 2- to 4-fold increase in risk for breast cancer. Other, less common variants also influence cancer risk. As with HBOC and Lynch, NCCN recommendations exist for breast and colorectal cancer surveillance and are dependent on individual, family, and the specific mutation.
• Cardiology Risk
  We are currently screening one gene, LDLR, for pathogenic variants which are associated with Familial Hypercholesterolemia. Families with Familial Hypercholesterolemia have an increased risk for elevated cholesterol that is not manageable by normal diet. This condition typically requires medication to decrease health risks.
• There are other inherited cancer syndromes that are screened for on the HOP genetic screening panel, but these are much less common and the risk and cancer type(s) varies depending upon the gene and variant.

HOP’s current panel of genes is listed below.

An inherited cancer syndrome is a disorder in which there is a higher-than-normal risk to develop certain types of cancer. Inherited cancer syndromes are caused by pathogenic and likely pathogenic variants (changes) in certain genes passed from parents to children. Rarely, a variant was not inherited but occurred during early embryogenesis.

In an inherited cancer syndrome, certain patterns of cancer may be seen within families. These patterns include having several close family members (such as a parent, sibling, and child) with the same type of cancer or related cancers (for example, breast and ovarian cancer with a BRCA1 variant), developing cancer at an early age, or having two or more types of cancer develop in the same person.

(Source: National Cancer Institute)

HOP is a research study and does testing that is not as complete as the testing that would be provided by standard clinical laboratories for high-risk individuals. This is because HOP’s goal is to screen participants at average risk. As such, high risk individuals that would normally be referred to genetic counselors by their provider for standard of care should continue to be referred for formal genetics evaluation to determine cancer risk and if additional genetic testing is indicated.

HOP is intended for the general public that is, adults who DO NOT have a strong family history of cancer, or early age of onset (generally under age) cancers. Individuals who have strong family histories or early onset should be referred for formal genetics evaluation to determine cancer risk and review clinical genetic testing options.

If a HOP participant has a pathogenic (positive result), an OHSU genetic counselor will contact the participant by phone to deliver the results, and provide a consult to review personal and family history, cancer risks associated with the variant, medical management recommendations, and inheritance. Cancer risks and management recommendations vary by gene and variant.

Participants will receive a results packet from an OHSU genetic counselor once the genetic counselor has reviewed the result with the participant on the phone. The packet is intended for the participant and for sharing with their healthcare providers and family members. If a participant requests the report to be shared directly with their physician or others at the time of genetic consult, a release of information will be mailed to the participant to complete and return. Participants will need an OHSU Medical Record Number (MRN) in order to receive a positive result and will be assigned an MRN if they don’t have one already.

The participant will receive the information below via mail after their genetic consult:

• copy of test result detailing the gene and pathogenic variant or likely pathogenic variant
• result letter to summarize the consult
• risk and management guidelines based on result and family history
• details to share with family members about their risk and testing options
• resources about organizations that support people with their type of inherited cancer syndrome
• how to access the genetic counselor in the future
• information about additional support that can be accessed through the HOP Participant Navigator.

The genetic counselor is available at any time a HOP participant has follow up questions or concerns about their result, further genetic counseling or screening.

If a participant has a negative result from the HOP study for genetic screening for the inherited cancer syndromes panel, they will receive an email from HOP that informs them a new result is available and be given instructions for access. A negative results report will be posted in the “results” tab, within the participant’s secure Healthy Oregon Project mobile application.

Participants with a negative result will not have an OHSU medical record and their result will highlight the following:

• Test result is negative, no detected inherited genetic changes in any of the genes covered by this test.
  • It is extremely unlikely that this participant will have one of the inherited cancer syndromes screened for by the HOP test.
• This result does not:
  • significantly change the personal risk of developing cancer compared to others in the general population.
  • mean that the participant will never develop cancer
• The test does not:
  • screen for all inherited genetic changes that cause cancer and lists the genes that were tested.
  • account for other factors that contribute to cancer risk, such as smoking, poor diet, or obesity.

OHSU Genetic Counseling
An OHSU genetic counselor will contact participants who have a positive result through the HOP study and will provide the result and any applicable NCCN management guidelines. The genetic counselor will also take a family and health history.

After their consult with the genetic counselor, the participant will receive a results packet that includes their result letter, a family letter, and information about the HOP study’s Participant Navigator.

The genetic counselor is available at any time a HOP participant has follow up questions or concerns about their result, further genetic counseling or screening.

HOP Participant Navigator
The HOP Participant Navigator is available to help participants with positive results access resources such as:

• location of primary care providers in their community, if participants do not already have one
• enrollment in health insurance
• application for financial assistance for health insurance copays
• connection to other programs that offer assistance, such as; support groups, behavioral health services and health advocacy organizations.
• genetic counseling resources and high-risk clinics that can be found in participant’s healthcare system and/or community

The Participant Navigator is not a medical provider and does not provide medical advice. If participants need medical or specific genetic advice, participants will need to ask their provider or talk with their provider or a genetic counselor. Participants are able to contact the OHSU genetic counselor with follow up questions or concerns.

Participants can contact the Participant Navigator at any time if a question comes up or participants need help finding services or resources. The Participant Navigator will contact participants one month after receiving results from the genetic counselor and again in six months.