Colorectal Cancer Risk Perception on the Basis of Genetic Test Results in Individuals at Risk for Lynch Syndrome

Abstract

A B S T R A C T PurposeLynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. Patients and MethodsA total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. ResultsOf the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as "high" or "very high" compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome-associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. ConclusionPatients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.

Cancer screening behaviors and risk perceptions among family members of colorectal cancer patients with unexplained mismatch repair deficiency

“…This is particularly surprising given that almost 70% of our participants perceived their risk of developing CRC to be higher or much higher than other people their age based on their family history. This rate is concordant with the 62% previously described by Grover et al [23] among individuals who met the Revised Bethesda Guidelines and had an indeterminate genetic test result; however, it is lower than the 90% who perceived high or very high risk for having CRC among patients with pathogenic mutation in the MMR genes.…”

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…It is characterised by an increased predisposition to most notably CRC and endometrial cancer, but also gastric cancer, ovarian cancer, hepatobiliary tract cancer, urinary tract cancer, brain cancer and skin cancers, and the cancers often occur at a younger age (See Fig. 1) (Aarnio et al, 1999;Abdel-Rahman et al, 2006;Grover et al, 2009;Hampel et al, 2005;Vasen et al, 2007;Vasen et al, 2001b). This risk varies depending both on the affected MMR gene and on the gene loci involved (Plaschke et al, 2004;ten Broeke et al, 2015;Vasen et al, 2001a;Wijnen et al, 2009).…”

“…2) . However, in clinical practice detailed family histories can be limited by recall bias, time constraints, an unwillingness to discuss genetic illnesses within families and patients (Aarnio et al, 1999;Abdel-Rahman et al, 2006;Grover et al, 2009;Hampel et al, 2005;Vasen et al, 2007;Vasen et al, 2001b). N.B.…”

Microsatellite instability in colorectal cancer: from molecular oncogenic mechanisms to clinical implications

“…The mean age at diagnosis for CRC is 43-46 years for MSH2 or MLH1 mutations carriers [15,80,147], and 51-57 years for MSH6 mutation carriers [15,80]. Regarding MLH1 and MSH2 mutation carriers, the lifetime risk for CRC is estimated to be 60-80% [2,69,75,174].…”