Michele C. Gornick

How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study.

Aim: To assess customer comprehension of health-related personal genomic testing (PGT) results. Methods: We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimers disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. Results: Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1-97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6-74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥60 years) was associated with lower comprehension scores. Conclusions: Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics.

Adiponectin gene and risk of colorectal cancer

Background:Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.Methods:The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case–control study in Israel.Results:No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88–1.23.Conclusion:The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel.

Direct-to-Consumer Genetic Testing: User Motivations, Decision Making, and Perceived Utility of Results

Background/Aims: To describe the interests, decision making, and responses of consumers of direct-to-consumer personal genomic testing (DTC-PGT) services. Methods: Prior to 2013 regulatory restrictions on DTC-PGT services, 1,648 consumers from 2 leading companies completed Web surveys before and after receiving test results. Results: Prior to testing, DTC-PGT consumers were as interested in ancestry (74% very interested) and trait information (72%) as they were in disease risks (72%). Among disease risks, heart disease (68% very interested), breast cancer (67%), and Alzheimer disease (66%) were of greatest interest prior to testing. Interest in disease risks was associated with female gender and poorer self-reported health (p < 0.01). Many consumers (38%) did not consider the possibility of unwanted information before purchasing services; this group was more likely to be older, male, and less educated (p < 0.05). After receiving results, 59% of respondents said test information would influence management of their health; 2% reported regret about seeking testing and 1% reported harm from results. Conclusion: DTC-PGT has attracted controversy because of the health-related information it provides, but nonmedical information is of equal or greater interest to consumers. Although many consumers did not fully consider potential risks prior to testing, DTC-PGT was generally perceived as useful in informing future health decisions.

A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories

Purpose:While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization.Methods:Surveys and follow-up interviews were conducted with laboratories offering exome and/or genome sequencing to support a research program or for routine clinical services. The 73-item survey elicited multiple choice and free-text responses that were later clarified with phone interviews.Results:Twenty-one laboratories participated. Practices highly concordant across all groups included consent documentation, multiperson case review, and enabling patient opt-out of incidental or secondary findings analysis. Noted divergence included use of phenotypic data to inform case analysis and interpretation and reporting of case-specific quality metrics and methods. Few laboratory policies detailed procedures for data reanalysis, data sharing, or patient access to data.Conclusion:This study provides an overview of practices and policies of experienced exome and genome sequencing laboratories. The results enable broader consideration of which practices are becoming standard approaches, where divergence remains, and areas of development in best practice guidelines that may be helpful.Genet Med advance online publication 03 Novemeber 2016

Impact of Non-Welfare Interests on Willingness to Donate to Biobanks An Experimental Survey

The ethical debate surrounding biobanks has focused on protecting donors’ welfare and privacy. However, little attention has been given to the ethical significance of donor interests that go beyond privacy and welfare (non-welfare interests [NWIs]), such as their concerns about the moral or religious implications of researchers using their donated samples. Using an experimental survey design with 1,276 participants recruited via Amazon Mechanical Turk (MTurk), we studied the potential impact of eight NWI scenarios on people’s attitudes toward research studies being performed on samples donated to biobanks by assessing willingness to donate, attitudes toward disclosure of NWIs, impact of timing and format of disclosure (number of NWIs disclosed on a page), and participant factors associated with willingness to donate. Baseline willingness to donate to biobanks prior to any mention of NWIs was comparable with previous studies, at 85% to 89%. Most participants wanted NWI disclosures prior to donation to biobanks, but far fewer favored specific consent. Overall pattern of responses showed that as participants receive more information about NWIs, willingness to donate decreases in a scenario dependent manner. Specifically, NWI concerns about profit seeking research and insurance risk assessment had the strongest impact, even greater than controversial issues such as reproductive research, regardless of political, religious, and most other characteristics of respondents. Based on the results, a schema of NWI types is proposed that could be used for further research and policy discussions.

Inflammatory bowel disease and familial adenomatous polyposis.

BACKGROUND Inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP) are uncommon diseases and both are associated with marked increased risk of colorectal cancer. METHODS We present a patient diagnosed in parallel with ulcerative colitis and FAP. Mutational analysis of the APC germline and somatic DNA was performed by sequencing. RESULTS This patients phenotype consisted of polyps only on the right side of the colon (cecum and ascending colon) whereas the area affected by ulcerative colitis (descending colon and rectum) was free of polyps on endoscopy and microscopic adenomas on histology. This raises the possibility that mosaicism or inflammation in the presence of active ulcerative colitis modified the phenotypic expression of adenomatous polyposis in the left colon. Mosaicism was excluded by DNA analysis. DISCUSSION This case of a patient diagnosed with both inflammatory bowel disease and familial adenomatous polyposis offers potential insights into the distinct pathogenesis of cancer susceptibility within these syndromes, and suggests that a collision of phenotypes may influence their mutual presentation. Both of these conditions independently increase the risk of colorectal cancer.

Interpretations of the Term “Actionable” when Discussing Genetic Test Results: What you Mean Is Not What I Heard

In genomic medicine, the familiarity and inexactness of the term “actionable” can lead to multiple interpretations and mistaken beliefs about realistic treatment options. As part of a larger study focusing on public attitudes toward policies for the return of secondary genomic results, we looked at how members of the lay public interpret the term “medically actionable” in the context of genetic testing. We also surveyed a convenience sample of oncologists as part of a separate study and asked them to define the term “medically actionable.” After being provided with a definition of the term, 21 out of 60 (35%) layperson respondents wrote an additional action not specified in the provided definition (12 mentioned “cure” and 9 mentioned environment or behavioral change) and 17 (28%) indicated “something can be done” with no action specified. In contrast, 52 surveyed oncologists did not mention environment, behavioral change, or cure. Based on our findings, we propose that rather than using the term “actionable” alone, providers should also say “what they mean” to reduce miscommunication and confusion that could negatively impact medical decision-making. Lastly, to guide clinicians during patient-provider discussion about genetic test results, we provide examples of phrasing to facilitate clearer communication and understanding of the term “actionable.”

Family History Collection Practices: National Survey of Pediatric Primary Care Providers

While family history (FH) collection is a core responsibility of pediatric primary care providers (PCPs), few details about this practice are known. We surveyed a random national sample of 1200 pediatricians and family medicine physicians about FH collection practices. A total of 86% of respondents (n = 289 pediatricians; n = 152 family medicine physicians) indicated that they collect a FH “always” or “most of the time” with 77% reporting collection at the first visit, regardless of whether it is a health maintenance or problem-focused visit. Less than half ask about relatives other than parents, siblings, or grandparents (36.3%). Among respondents, 42% routinely update the FH at every health maintenance visit while 6% updated FH at every visit. Pediatric PCPs use a variety of methods to collect a FH that is limited in scope and variably updated. Our results suggest that interventions are needed to help pediatric PCPs collect a systematic, efficient, and updated FH.

Knowledge Regarding and Patterns of Genetic Testing in Patients Newly Diagnosed With Breast Cancer Participating in the iCanDecide Trial: Knowledge of Breast Cancer Genetic Testing

The current study reports rates of knowledge regarding the probability of a BRCA1 and/or S pathogenic variant and genetic testing in patients with breast cancer, collected as part of a randomized controlled trial of a tailored, comprehensive, and interactive decision tool (iCanDecide).

Estimating probability of germline mismatch repair mutations in colorectal cancer patients with microsatellite stable tumors

identified in patients from families that met the Amsterdam Criteria (AC I/II), whereas 3 mutations were found in patients from families that were AC I/II negative. The modified likelihood for a germline mutation (+LRmod )i n an AC I/II patient was 1.56 (95% CI: 0.47 - 5.18) and the modified negative likelihood ratio (-LRmod )f or ap atient not meeting the AC I/II criteria was 0.81 (95% CI: 0.39 1.69). We quantified the meaning of the AC I/II criteria to guide clinical choices about genetic testing in MSS tumors by multiplying the pretest odds by the +LRmod and the -LRmod. The probability of a mutation was modified from a baseline of 11.4% to 16.7% in AC I/II families, compared to 9.4% in AC I/II-negative families. Conclusions Germline MMR testing in high risk patients with MSS colorectal tumors identifies mutations in a small, but meaningful proportion of patients. The diagnostic yield is dependent on the strength of the family history. Modified likelihood ratios can be helpful to quantify the probability of a positive gene test for Lynch Syndrome, and can be applied to pre-test probabilities derived from clinical models.