Cancer Genetic Risk Assessment

Categorizing Risk

The purpose of genetic risk assessment is to identify individuals at elevated cancer risk who may benefit from genetic testing, additional screening or preventive interventions. Using clues from the personal and family history, you can classify an individual as average (general population), increased (moderate), or high (strong) risk.

General Criteria for Average, Increased (Moderate) and High (Strong) Cancer Risk

Average Risk for Cancer

An absence of the red flags and risk factors associated with increased or high risk.

Increased (Moderate) Risk for Cancer

A patient may be at increased risk for cancer because of a family history contribution, personal or lifestyle risk factors, or a combination of the two. Family histories suggestive of increased risk may show familial clustering of cancer but do not meet the criteria for high risk.

Family history: 

  • One first-degree relative with common cancer at average age only
  • One first- and one second-degree relative or two second-degree relatives with common cancer at average ages only

In addition to family history, personal history risk factors can increase an individual's risk of developing cancer. Consider the following risk factors:

  • Medical history
  • Patient race or ethnicity
  • Reproductive history
  • Lifestyle, behaviors, and exposures
High Risk for Hereditary Cancer

Individuals at high risk for a hereditary cancer syndrome typically have one or more of these general family hitory features:

  • 3 or more relatives with similar or related cancers
  • 2 generations of cancer cases, and
  • At least 1 individual diagnosed at a younger than usual age
  • Known hereditary cancer mutation or clinical diagnosis
  • Presence of certain cancers in patietn or close blood relatives (e.g., ovarian, pancreatic, triple negative breast cancer ≤ 60, male breast cancer, metastatic prostate)
  • Other characteristic features may include:
    • At least 1 individual with bilateral or multiple primary tumors
    • At least 1 relative with a rare tumor or rare presentation, or a presentation associated with hereditary cancer
    • Presence of other nonmalignant features
    • Absence of environmental risk factors

Adapted from: Schneider, K. (2012). Counseling about Cancer: Strategies for Genetic Counseling. Hoboken, New Jersey: John Wiley & Sons, Inc.

 

Breast Cancer Genetic Risk Stratification

Risk Level

Personal and Family History Evidence

Average

  • No first- or second-degree relatives^ with breast or ovarian cancer; OR
  • More distant relatives with a breast cancer diagnosis or diagnoses after age 50

Increased (moderate)

  • One or two first- or second-degree relatives with breast cancer diagnosis after age 50

High (strong)

  • Known pathogenic variant (mutation) in the family
  • Somatic tumor testing suggesting a germline pathogenic variant
  • Diagnosis in patient, or first- or second-degree relative with
    • breast cancer younger than 45
    • triple negative breast cancer diagnosed at age 60 or younger
    • primary cancer of both breasts
    • ovarian, pancreatic, metastatic prostate, or male breast cancer at any age
    • breast cancer or high grade prostate cancer diagnosis at any age and Ashkenazi Jewish ancestry
  • Two or more first- or second-degree relatives on same side of family with breast cancer, if at least one was diagnosed before age 50
  • Three or more first- or second-degree relatives on same side of family with breast cancer at any age
^ First-degree relatives are parents, children, and siblings. Second-degree relatives are grandparents, grandchildren, uncles and aunts.

 

Please see NCCN Genetic/Familial High Risk Assessment: Breast, Ovarian and Pancreatic: Hereditary Testing Criteria for more details, including family history presentation for rare syndromes.

In addition to family history, personal history risk factors can increase an individual’s risk of developing cancer. For example, a medical condition such as breast atypia mayincrease breast cancer risk. Behavioral or lifestyle choices (e.g., cigarette use, alcohol consumption) can affect cancer risk generally; reproductive history can affect a woman’s breast cancer risk (e.g., age at menarche).

Colorectal Cancer Genetic Risk Stratification

Risk Level

Personal and Family History Evidence

Average

  • No first- or second-degree relatives^ with colorectal cancer, advanced adenomatous or sessile serrated colon polyps (>1 cm)

Increased (moderate)

  • Personal history of CRC, IBD, advanced adenoma or sessile serrated polyp
  • One or more first-degree relatives with colorectal cancer, advanced adenoma or sessile serrated at any age; OR
  • One or more second-degree relatives with colorectal cancer < 50 years

High (strong)

  • Known pathogenic variant (mutation) in the family
  • Somatic tumor testing suggesting a hereditary cancer syndrome
  • CRC with MSI-High histology diagnosed ≤ 60 years
  • Diagnosis in patient, or first- or second-degree relatives with
    • CRC younger than 50 years
    • Two primary cancers: CRC or endometrial cancer and an associated cancer*
    • A rare presentation such as >10 adenomas or unusual polyp histology
  • Two or more first- or second-degree relatives on same side of family with CRC or Lynch-associated cancers, if at least one was diagnosed before age 50
  • Three or more first- or second-degree relatives on same side of family with CRC or Lynch-associated cancers at any age
^ First-degree relatives are parents, children, and siblings. Second-degree relatives are grandparents, grandchildren, uncles and aunts.
* Lynch syndrome-related cancers include colorectal, endometrial, gastric, ovarian,  pancreas, bladder, biliary tract, urothelial, small bowel, prostate, breast, brain (usually glioblastoma), as well as sebaceous skin lesions and keratoacanthomas.

 

Please see NCCN Genetic/Familial High Risk Assessment: Colorectal Assessment for Hereditary CRC Syndromes for more details. 

In addition to family history, personal history risk factors can increase an individual’s risk of developing cancer. For example, behavioral or lifestyle choices (e.g., cigarette use, alcohol consumption) can affect cancer risk generally; diet and inflammatory bowel disease can increase the risk of CRC.

Cancer Genetics Risk Assessment Models

Risk assessment tools and models can help identify patients at increased risk. Different models may provide slightly different risk numbers, depending on the factors considered in the algorithm.

In addition to the models and risk calculators listed below, providers can also look to the literature for empiric risk estimates. This can be particularly helpful when assessing risk levels for a family that demonstrates increased risk based on clustering of cancer.

Cancer Genetic Red Flags Checklist. This tool includes a general list of red flags as well as breast and colon specific red flags.

 

Breast Cancer Risk Assessment Tools

Breast Cancer Risk Assessment Tool (National Cancer Institute). Considers personal history, reproductive history, and some family history to provide 5-year and lifetime risk estimates for breast cancer.

Breast Cancer Genetics Referral Screening Tool (Georgia Department of Public Health). Collects targeted family history information about breast and ovarian cancer. Screens for the appropriateness of a referral to cancer genetic services based on risk level. Includes a patient version.

NCCN Criteria for Further Genetic Risk Evaluation: Guidelines for Detection, Prevention and Risk Reduction of Breast/Ovarian and Colorectal Cancer.  Includes personal and family history features that should warrant consideration of a referral to cancer genetic services. Requires free account setup.

Tyrer-Cuzick Risk Assessment Tool (IBIS). Collects targeted personal and family history information and estimated 10-year and lifetime risk of breast cancer, as well as risk of HBOC.

For Patients

Family HealthLink (Ohio State University Medical Center). Collects personal and family history information to determine a risk estimate for cancer and cardiovascular disease.

Colon Cancer Risk Assessment Tools

Colon Cancer Risk Assessment Tool (National Cancer Institute). Considers personal history, diet, exercise, exposures, and some family history to provide 5-year, 10-year and lifetime risk estimates for colon cancer.

PREMM model. A clinical prediction algorithm that estimates the probability of an individual carrying a germline mutation for Lynch syndrome.

For Patients

Colon Cancer Risk Assessment Tool (Cleveland Clinic). Collects personal, behavioral, and family history information to determine a risk estimate for colorectal cancer.

3 Questions to Assess Your Familial Colorectal Cancer Risks (Columbia University). Asks three basic questions to determine if an individual is at increased risk.

 

Updated May 2020