Variations in predicted risks in personal genome testing for common complex diseases

Kalf, Rachel R. J.; Mihăescu, Raluca; Kundu, Suman; Knijff, Peter de; Green, Robert C.; Janssens, A. Cecile J.W.

doi:10.1038/gim.2013.80

Cited by 57 publications

(58 citation statements)

References 17 publications

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“…Many researchers and professional societies have expressed concerns about the unclear predictive ability and clinical utility of the tests; [1][2][3] others showed no evidence of adverse psychological or behavioral consequences. [4][5][6][7][8][9][10] Although the scientific studies conducted so far have indeed shown no evidence of adverse effects, they all had serious limitations that hampered the proper interpretation and generalizability of the findings.…”

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confidence: 99%

“…2 Most people have probably received risk estimates that were only slightly higher (or lower) than the average risk for a disease, and these were not sufficiently alarming to increase anxiety and distress. The findings of such studies can be generalized to other personal genome tests with limited predictive ability but not to tests that yield very informative test results.…”

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The hidden harm behind the return of results from personal genome services: a need for rigorous and responsible evaluation

Janssens

2015

Genetics in Medicine

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CommentaryWhether the delivery of genetic test results directly to consumers has harmful effects has been the subject of scientific debate since the first personal genome services became available. Many researchers and professional societies have expressed concerns about the unclear predictive ability and clinical utility of the tests;1-3 others showed no evidence of adverse psychological or behavioral consequences. [4][5][6][7][8][9][10] Although the scientific studies conducted so far have indeed shown no evidence of adverse effects, they all had serious limitations that hampered the proper interpretation and generalizability of the findings.Many studies were conducted among "early adopters" of personal genome services, who were most often white, better educated, and in better physical and mental health. [4][5][6][7] The largest study of its kind (n > 2,000) concluded that these early adopters may better understand the minor impact that genes have on the development of common diseases. 4,5 However, regarding the generalizability of their findings, the authors wrote that "given that [our sample] is quite homogenous (e.g., highly educated, high income), our conclusions may not be applicable to other groups of individuals should the market expand, or to the general population. " 5In a study reported in this issue of Genetics in Medicine, Hartz et al.8 investigate a population that is virtually the opposite of the early adopters. Of their population, 66% had levels of depression above clinical thresholds, all were nicotine-dependent smokers, and more than half were African American, did not have a college education, were unemployed, and had no health insurance. So far, so good. However, although the authors concluded that "even in an underserved population … subjects responded positively to personalized genetic results, " upon close analysis their results suggest that participants may not have understood the tests: The observed increase in smoking cessation attempts was unrelated to receiving test results of increased risk, and 95% of the participants considered their test results useful while they all received risks that were predicted for Caucasians, also the African-American customers.A major and unavoidable limitation of studies of consumer experiences with personal genome services is that tests for common diseases still have limited predictive ability.2 Most people have probably received risk estimates that were only slightly higher (or lower) than the average risk for a disease, and these were not sufficiently alarming to increase anxiety and distress. The findings of such studies can be generalized to other personal genome tests with limited predictive ability but not to tests that yield very informative test results.That even the return of results from highly predictive tests may not increase harm is often evidenced by citing the REVEAL study, 11 which investigated responses to receiving APOE results for the risk of Alzheimer disease. The study was conducted in children of patients with Alzheimer disease, ...

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The hidden harm behind the return of results from personal genome services: a need for rigorous and responsible evaluation

Janssens

2015

Genetics in Medicine

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“…Although the accuracy of the technology used is considered to be high, there are no agreed standards to which the company can conform for validating hundreds of simultaneous variant calls. There is also controversy about how to evaluate the accuracy of risks estimated using multiple variants or across ethnicities 2,3 . And consumers might not read or fully understand the company's clear statements that its tests identify only the most common genetic variants and cannot substitute for genetic testing ordered by physicians to assess specific indications, such as a family history of cancer.…”

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Regulation: The FDA is overcautious on consumer genomics

Green

Farahany

2014

Nature

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“…In addition, prostate cancer was one of the diseases included in direct-toconsumer genetic risk assessments for multiple diseases offered by deCODE, Navigenics, and 23andMe. 68 The offer of the all of the deCODE tests and the Navigenics test seems to have since been discontinued. In the United States, 23andMe no longer offers health-related genetic reports 69 ; in Canada and the United Kingdom, reports on over 100 conditions are offered, but prostate cancer is not listed.…”

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Multigene panels in prostate cancer risk assessment: a systematic review

Little

Wilson

Carter

et al. 2016

Genetics in Medicine

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Prostate cancer is the fourth most common malignancy worldwide, and the second most common among men.1 In 2014, it was estimated that more than a quarter of a million new cases were diagnosed in North America and that the disease accounted for more than 33,000 deaths. 2,3 These numbers are likely to increase with the aging of the population. On the basis of data from the Surveillance, Epidemiology, and End Results program, more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004-2005 than in the mid-late 1990s, and disparity between ethnic groups in cancer stage at diagnosis decreased. 4 Apart from age, 5 ethnic group, 5,6 and family history, 7-9 the risk factors associated with prostate cancer are unclear, 5 making primary prevention difficult. Prostate cancer is currently considered to be a complex, multifactorial disease, and the vast majority of familial clustering is attributed to the interaction of multiple shared susceptibility genes with moderate to low penetrance and shared environmental factors within these families.The natural history of prostate cancer is highly variable. 10 In a large proportion of men the disease is indolent, and it is difficult to predict which tumors will be aggressive. The value of aggressive management for localized prostate cancer is debated, [11][12][13][14] and only a small proportion of men with early-stage prostate cancer die from the disease within 10 to 15 years of diagnosis. Developing tools to differentiate aggressive and indolent disease is of key importance.Prostate-specific antigen (PSA) screening was introduced in the late 1980s.15 Meta-analyses of seven randomized controlled trials (RCTs) of screening using PSA testing alone or in combination with digital rectal examination suggested no evidence of benefit in reducing mortality 16,17 and some evidence of harm from overdiagnosis.17 Amid substantial debate, 18-20 the argument has been made for developing more accurate screening tests, including possible genetic markers. Purpose: Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels.Methods: Data sources comprised MEDLINE, Cochrane CEN-TRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers. Results:Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs.All had poor discriminative ability (overall area under receiver-operator characteristic curves, 5...

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Variations in predicted risks in personal genome testing for common complex diseases

Cited by 57 publications

References 17 publications

The hidden harm behind the return of results from personal genome services: a need for rigorous and responsible evaluation

The hidden harm behind the return of results from personal genome services: a need for rigorous and responsible evaluation

Regulation: The FDA is overcautious on consumer genomics

Multigene panels in prostate cancer risk assessment: a systematic review

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