Cancer Genetic Risk Assessment

Categorizing Risk

The purpose of genetic risk assessment is to identify individuals with a greater than average genetic contribution to disease, who may benefit from additional screening and 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 relatives or two second-degree relatives with common cancer at average ages only

Consider the following risk factors in personal history:

  • 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 history 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
  • Other characteristic features 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. Hobokken, New Jersey: John Wiley & Sons, Inc.

 

Breast cancer genetic risk stratification

Risk Level

Family History Evidence

Average

  • No first- or second-degree relatives^ with breast or ovarian cancer; OR
  • One second-degree female relative with breast cancer diagnosis after age 50

Increased (moderate)

  • One or two first- or second-degree relatives with breast cancer diagnosis after age 50; OR
  • Two first- or second-degree relatives with pancreatic or high grade prostate cancer

High (strong)

  • One or more first- or second-degree relatives with
    • breast cancer younger than 45
    • triple negative breast cancer diagnosed at age 60 or younger
    • primary cancer of both breasts
    • breast and ovarian cancer in same relative, or
    • ovarian or male breast cancer at any age
  • 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, pancreatic, or high grade prostate cancer at any age
^ First-degree relatives are parents, children, or siblings. Second-degree relatives are grandparents, grandchildren, uncles & aunts.

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; reproductive history can affect a woman’s breast cancer risk (e.g., age at menarche).

Colorectal cancer genetic risk stratification

Risk Level

Family History Evidence

Average

  • No first- or second-degree relatives^ with colorectal cancer; OR
  • One second-degree relative with colorectal cancer diagnosis after age 50

Increased (moderate)

  • One first-degree relative with colorectal cancer <50; OR
  • Two first- or second-degree relatives with colorectal cancer at any age; OR
  • 1-10 adenomatous polyps

High (strong)

  • One or more first-degree relatives with
    • Colorectal cancer and endometrium, small bowel, stomach, hepatobiliary, renal pelvic, or ureteral cancer in the same individual
    • Colorectal cancer witha first-degree relative with endometrium, small bowel, stomach, hepatobiliary, renal pelvic, or ureteral cancer, with one of the cancers being diagnosed before age 50
    • Colorectal cancer with2 first- or second-degree relatives with endometrium, small bowel, stomach, hepatobiliary, renal pelvic, or ureteral cancer at any age
    • Colorectal cancer tumor histology suggestive of Lynch syndrome (absence of mismatch repair proteins on immunohistochemistry or showing microsatellite instability)
    • 10 or more colon polyps
^ First-degree relatives are parents, children, or siblings. Second-degree relatives are grandparents, grandchildren, uncles & aunts.

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 Tools, Calculators, and 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.

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 and screens for the appropriateness of a referral to cancer genetics professionals based on risk level. Includes a patient version.

Summary of Validated Tools for Hereditary Breast and Ovarian Cancer Syndrome Risk Assessment (United States Preventative Services Task Force). Lists models recommended by USPSTF that estimate risk for hereditary breast and ovarian cancer syndrome to guide referrals.

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.

For Patients

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