Pathogenic Variants in Less Familiar Cancer Susceptibility Genes: What Happens After Genetic Testing?

Purpose: As genetic testing expands, patients are increasingly found to carry pathogenic variants in cancer susceptibility genes that are less familiar to most clinicians, specifically genes other than those causing hereditary breast ovarian cancer syndrome ( and ) and Lynch syndrome. Little is known about the subsequent behaviors of such patients in terms of managing cancer risks and informing relatives.

Methods: All adult patients who were counseled and tested at the Stanford Cancer Genetics Clinic from January 2013 to July 2015 and had a pathogenic variant in a non-, non-Lynch syndrome gene were invited to participate in a telephone interview about adherence to risk-reducing recommendations, genetic testing by relatives, and new cancer incidence.

Results: Fifty-seven (40%) of 142 eligible patients were successfully contacted, and all 57 patients participated; median follow-up was 677 days (range, 247 to 1,401 days). Most patients (82%; 95% CI, 70% to 90%) recalled that a risk-reducing intervention (screening, medication, or surgery) was recommended, and most patients (85%; 95% CI, 72% to 93%) adhered to the recommendation. Nearly all patients (91%; 95% CI, 81% to 97%) shared results with relatives, and most patients (78%; 95% CI, 64% to 88%) reported that a relative was subsequently tested. During the follow-up period, 9% of patients (95% CI, 3% to 19%) developed second cancers, and in 14% of patients (95% CI, 7% to 26%), a first-degree relative developed cancer, some of which were detected by recommended screening.

Conclusion: Patients with a pathogenic variant in a less familiar cancer susceptibility gene report high adherence to risk-reducing interventions. Furthermore, in the 57 carriers and subsequently tested relatives with two years of follow-up, a total of three cancers (one in a proband and two in relatives) were detected through interventions recommended on the basis of the pathogenic variant. These results suggest a potential benefit of genetic counseling and testing for pathogenic variants in less familiar genes.