Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

Abstract

Family history-based risk assessment (FHRA) is a genetic tool for identifying those at risk of disease. Genome-wide association studies have shown that single nucleotide polymorphisms (SNP) are statistically associated with low-to moderate-level risks of diseases. There has been limited study of complementarity for these two assessment methods. We sought to compare cancer risk categorizations from FHRA and from Navigenics Personal Genome Screening (PGS). We compared FHRA with PGS for breast (22 females), prostate (22 males), and colon cancer (44 males and females) assessed by kappa (j) statistic. We also assessed each participant's hereditary risk based on clinical criteria and/or gene-test results. Both FHRA and PGS placed 59%, 68% and 44% of participants into the same risk categories for breast, prostate, and colon cancer, respectively. Overall, however, there was little concordance in FHRA versus PGS for all three cancer risks (jo0.2). FHRA assigned 22 with hereditary risk compared with PGS, which identified one as high risk (Po0.0001). We assessed nine with hereditary colorectal cancer risk, five with germline mutations, but none were classified as PGS high risk (P¼0.0001). FHRA and PGS may be complementary tools for cancer risk assessment. However, evaluation of family history remains the standard to evaluate an individual's cancer risk until further research.

Risk estimates for complex disorders: comparing personal genome testing and family history

“…The results of our study are consistent with those found by Heald et al, 14 which reported poor concordance between risk assessment methods for three conditions tested in Navigenics PGT (breast cancer, prostate cancer, and colon cancer). We expand on their work by analyzing more conditions included in the PGT panel and in a larger sample of individuals.…”

“…This is reflected by our finding that for the majority of the conditions, significantly more individuals were grouped into higher risk categories by PGT risk assessment (see Supplementary Table S1a,b online). For a more accurate comparison of risks between PGT and family history, further long-term studies should be undertaken looking at In summary, our data along with other studies 13,14 suggest that these two methods of risk assessment for common complex disorders provide different and perhaps complementary information. Our study provides one of the most extensive analyses to date of concordance between risk estimates provided by PGT and family history assessments and finds little to no concordance for 20 of the multifactorial conditions included in Navigenics PGT.…”

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

“…There are concerns that overstated claims create unrealistic consumer expectations, may harm privacy and induce confusion and anxiety. For example, one recent study 3 finds little concordance in results for cancer risk from personal genome screening and the family history-based risk assessment commonly used in genetic counselling services. There have been several initiatives by professional or advisory bodies to identify the issues for managing such tests, most notably by the European Society of Human Genetics (ESHG) 4 but also, for example, in the UK by the Human Genetics Commission 5 and in the United States by the American Medical Association.…”

Is It Desirable that I Must Disclose My Genetic Data to Swiss Private Medical Insurances?

“…It is also important to note that, in spite of the excitement surrounding the genomic era, genetic prediction should not be given undue weight. Brandie et al [14] compared family history and genomic screening in the assessment of breast, prostate, or colorectal cancer risk, and concluded that genetic data is not a substitute for family history, and, in fact, family history remains the clinical standard.…”