Race/ethnicity did not influence the levels of distress and uncertainty experienced by persons undergoing multigene testing to evaluate for hereditary cancer susceptibility, according to results of a survey-based study reported in Cancer.1

Multigene panels are replacing single-gene or single-gene syndrome panels in the setting of hereditary cancer genetic testing. However, the former method is associated with an increased likelihood of identifying genetic variants of unknown significance (VUS), as well as pathogenic variants of genes with less well established clinical associations, including genes classified as being of moderate risk which are estimated to increase cancer risk by a factor of 2 to 5.

In commenting on the latter observation, the study investigators noted, “Some experts have expressed concern that testing moderate-risk genes may lead to patient confusion, uncertainty, and psychological distress.”

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This prospective study evaluated levels of distress and uncertainty using the Multidimensional Impact of Cancer Risk Assessment (MICRA) tool2 in a large, diverse cohort that underwent genetic testing with a 25- or 28-gene panel between July 2014 and November 2016 at 3 genetic cancer clinics associated with large, academic medical centers. All participants had an estimated pretest probability of being positive for a pathogenic variant of 2.5% or higher and received genetic counseling prior to genetic testing. The researchers administered the MICRA survey tool at 3 months after the results of genetic testing were disclosed to the patient.

Of the 2000 participants enrolled in the study, a high-risk pathogenic variant was uncovered in 6.9%, a moderate-risk variant in 5.3%, 1 or more VUS with no high- or moderate-risk variants in 36.1%, and no increased risks variant or VUS in 51.8%, which corresponded to a negative result. 

At least 1 question on the MICRA survey was completed by 1264 (66.4%) participants at 3-month follow-up, which included 7.4%, 5.5%, 35.0%, and 52.1% of persons with results falling into the category of pathogenic variant, moderate-risk variant, VUS, and negative results, respectively. Whether a participant responded to the survey was determined to be independent of the test result. However, factors shown to be associated with an increased likelihood of survey completion included female sex, increased age, higher level of education, non-Hispanic White race, being able to speak English, and no history of cancer.

Those who responded to the MICRA survey had a mean age at testing of 52.2 years, 79.8% were female, and approximately 70% had a history of cancer. The race/ethnicity of these patients was characterized as non-White Hispanic (44.9%), Hispanic (37.3%), Asian (9.7%), Black or African American (3.2%), and multiple/other (4.9%). Some college or at least a college degree was reported by 18.3% and 45.3% of participants, respectively.

A key study finding was that the majority of responders showed low overall levels of distress and uncertainty using the MICRA tool, including 74.4% of those with a pathogenic variant, 82.4% with a moderate risk variant, 94.1% in the VUS category, and 94.9% with negative testing results.

Multivariate analyses adjusting for potential confounders, including sex, race/ethnicity, age in years, cancer affected status, clinic site, education level, and language ability demonstrated that overall MICRA scores were significantly higher for those with high- (expected ratio [ER], 1.85; 95% CI, 1.590-2.158; P < .001) or moderate-risk pathogenic variants (ER, 1.56; 95% CI, 1.310-1.859; P < .001) compared with participants with negative results. Nevertheless, a comparison of overall (P =.125) and subset MICRA scores separately evaluating distress and uncertainty for those with high- and moderate-risk pathogenic variants did not show significant differences.

The latter finding was “contrary to our stated hypothesis that moderate-risk carriers would have higher uncertainty than high-risk carriers,” noted the study investigators.

In addition, overall MICRA scores were not significantly different for those identified as having 1 or more VUS compared with those with negative results (P =.103), although participants falling into this category were significantly more likely than those with negative results to have higher MICRA uncertainty subset scores (P =.045).

While neither language nor race/ethnicity were significantly associated with MICRA scores, persons with a college education or higher had significantly lower overall MICRA scores compared with those with a high school education or less (ER, 0.852; 95% CI, 0.748-0.969; P =.015).  

The study investigators noted, “This study offers novel, significant insights into psychological outcomes after multigene panel testing and helps to identify concerns of patients undergoing panel testing.”

They further noted, “Patients’ educational level should be considered when one is approaching panel testing and strategies for effective counseling used to meet the psychological needs that may arise.”

Disclosures: Multiple authors declared affiliation with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


1. Culver JO, Ricker CN, Bonner J, et al. Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients. Cancer. Published online December 15, 2020. doi:10.1002/cncr.33357

2. Cella D, Hughes C, Peterman A, et al. A brief assessment of concerns associated with genetic testing for cancer: the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire.Health Psychol. 2002;21(6):564-572. doi:10.1037/0278-6133.21.6.564