Abstract
Awareness of ethical issues that may be raised by the implementation of nutrigenetic/nutrigenomic (NGx) testing and personalized nutrition, at an individual or a public health level, is crucial to ensure the latter's sound and effective implementation. NGx tests that are currently offered or developed have different natures and scopes. We provide an example of NGx testing on the MTHFR gene to illustrate the current challenges when it comes to grasp the meaning of the results of such testing. In addition, NGx testing is developed within an evolving landscape of new genomic technologies and occurs at a time when public health policies mainly focus on preventive and predictive healthcare, with an emphasis on increased individual responsibility. The ethical issues raised by such a context and the genetic nature of NGx testing both should be carefully evaluated.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 American College of Medical Genetics and Genomics. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet. Med. 17(6), 505–507 (2015).
- 2 Centers for Disease Control and Prevention, Office of Public Health Genomics. ACCE model list of 44 targeted questions aimed at a comprehensive review of genetic testing (2010). www.cdc.gov/genomics/gtesting/acce/acce_proj.htm.
- 3 . Risks of nutrigenomics and nutrigenetics? What the scientists say. Genes Nutr. 9(1), 370 (2014).
- 4 National Human Genome Research Institute. Frequently asked questions about genetic testing (2015). www.genome.gov/19516567.
- 5 Reporting incidental findings in genomic scale clinical sequencing – a clinical laboratory perspective. A report of the association for molecular pathology. J. Mol. Diagn. 17(2), 107–177 (2015). • An extensive review from the Incidental Findings Working Group of the Association for Molecular Pathology (AMP) Clinical Practice Committee and the Whole Genome Analysis Working Group. It describes the new challenges raised by next-generation sequencing technology, its potential benefits, but also the potential harms that could result from reporting incidental findings to patients.
- 6 Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am. J. Hum. Genet. 94(6), 818–826 (2014).
- 7 . Next generation sequencing in psychiatric research: what study participants need to know about research findings. Int. J. Neuropsychopharmacol. 16(9), 2119–2127 (2013).
- 8 . Use of next generation sequencing technologies in research and beyond: are participants with mental health disorders fully protected? BMC Med. Ethics 13, 36 (2012).
- 9 Reporting results from whole-genome and whole-exome sequencing in clinical practice: a proposal for Canada? J. Med. Genet. 51(1), 68–70 (2014).
- 10 . Return of results: ethical and legal distinctions between research and clinical care. Am. J. Med. Genet. C Semin. Med. Genet. 166C(1), 105–111 (2014).
- 11 . To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts. Eur. J. Hum. Genet. 21(3), 248–255 (2013).
- 12 . Patients’ views on incidental findings from clinical exome sequencing. Appl. Transl. Genom. 4, 38–43 (2015).
- 13 . Returning pleiotropic results from genetic testing to patients and research participants. JAMA 311(8), 795–796 (2014).
- 14 . State of play in direct-to-consumer genetic testing for lifestyle-related diseases: market, marketing content, user experiences and regulation. Proc. Nutr. Soc. 72(1), 53–60 (2013).
- 15 Canadian College of Medical Geneticists. Direct-to-consumer (DTC) genetic testing in this country. A letter to the Honourable Rona Ambrose, P.C., M.P, Health Canada (2015). www.ccmg-ccgm.org/news-article-11.html?id=230amp;catid=122.
- 16 . Negotiating the boundary between medicine and consumer culture: online marketing of nutrigenetic tests. Soc. Sci. Med. 70(5), 744–753 (2010).
- 17 . Nutrigenomics: definitions and advances of this new science. J. Nutr. Metab. 2014, 202759 (2014).
- 18 . Expert views on critical success and failure factors for nutrigenomics. Trends Food Sci. Technol. 18(4), 189–200 (2007).
- 19 Guide and position of the international society of nutrigenetics/nutrigenomics on personalized nutrition: part 2 – ethics, challenges and endeavors of precision nutrition. J. Nutrigenet. Nutrigenomics 9(1), 28–46 (2016). •• A position paper by the International Society of Nutrigenetics/Nutrigenomics that acknowledges current scientific challenges and an urgent need for ethical, social and legal considerations in the development of nutrigenetic/nutrigenomic applications.
- 20 . The future direction of personalised nutrition: my diet, my phenotype, my genes. Proc. Nutr. Soc. 72(2), 219–225 (2013).
- 21 Interaction between polyphenols intake and PON1 gene variants on markers of cardiovascular disease: a nutrigenetic observational study. J. Transl. Med. 14(1), 186 (2016). • A good example of a nutrigenetic study targeting a gene and polymorphisms that are already known or studied for their contribution to the onset of cardiovascular diseases. Such a study shows how NGx is expected to be used to modulate pre-existing genetic risks.
- 22 . A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake. Genes Nutr. 10(1), 445 (2015).
- 23 . Celiac disease, inflammation and oxidative damage: a nutrigenetic approach. Nutrients 4(4), 243–257 (2012).
- 24 . Nutrigenetics and personalized nutrition: are we ready for DNA-based dietary advice? Per. Med. 11(3), 297–3017 (2014).
- 25 . Moving towards specific nutrigenetic recommendation algorithms: caffeine, genetic variation and cardiovascular risk. J. Nutrigenet. Nutrigenomics 9(2–4), 106–115 (2016).
- 26 . Dietary patterns, genes, and health: challenges and obstacles to be overcome. Curr. Nutr. Rep. 4, 82–87 (2015).
- 27 . Are research papers reporting results from nutrigenetics clinical research a potential source of biohype? Account Res. 19(5), 285–307 (2012).
- 28 . Use of nutrigenomics endpoints in dietary interventions. Proc. Nutr. Soc. 72(3), 348–351 (2013).
- 29 Nutrition research to affect food and a healthy life span. J. Nutr. 143(8), 1349–1354 (2013).
- 30 . The developmental environment, epigenetic biomarkers and long-term health. J. Dev. Orig. Health Dis. 6(5), 399–406 (2015).
- 31 . Nutrigenetic testing. Considerations for clinicians. Altern. Complement. Ther. 20(2), 80–83 (2014).
- 32 Biomarkers of nutrition for development-folate review. J. Nutr. 145(7), S1636–S1680 (2015).
- 33 . Folate-genetics and colorectal neoplasia: what we know and need to know next. Mol. Nutr. Food Res. 57(4), 607–627 (2013).
- 34 Reduction in neural-tube defects after folic acid fortification in Canada. N. Engl. J. Med. 357(2), 135–142 (2007).
- 35 . The MTHFR C677T polymorphism is related to plasma concentration of oxidized low-density lipoprotein in adolescents with cardiovascular risk factors. J. Nutrigenet. Nutrigenomics 8(3), 105–113 (2015).
- 36 A Phase II randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer's disease. J. Alzheimers Dis. 45(2), 395–405 (2015).
- 37 . Alzheimer's disease and epigenetic diet. Neurochem. Int. 78, 105–116 (2014).
- 38 . Does the MTHFR 677C–>T variant affect the recommended dietary allowance for folate in the US population? Am. J. Clin. Nutr. 89(4), 1269–1273 (2009).
- 39 . Folate and folic acid in the periconceptional period: recommendations from official health organizations in thirty-six countries worldwide and WHO. Public Health Nutr. 19(1), 176–189 (2016).
- 40 Evidence from a randomized trial that exposure to supplemental folic acid at recommended levels during pregnancy does not lead to increased unmetabolized folic acid concentrations in maternal or cord blood. J. Nutr. 146(3), 494–500 (2016).
- 41 Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case–control studies. Tumour Biol. 36(11), 8953–8972 (2015).
- 42 U.S. National Library of Medicine. MTHFR (2016). https://ghr.nlm.nih.gov/gene/MTHFR.
- 43 . MTHFR: addressing genetic counseling dilemmas using evidence-based literature. J. Genet. Couns.
doi:10.1007/s10897-016-9956-9957 (2016) (Epub ahead of print). •• Presents a brief background of the MTHFR polymorphisms and their clinical significance. The authors address the challenges that MTHFR testing can raise in genetic counseling. - 44 . Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians. Gene 571(1), 28–32 (2015).
- 45 Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: an updated meta-analysis and review. Nephrology (Carlton) 21(1), 5–12 (2016).
- 46 . B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci. Biobehav. Rev. 47, 307–320 (2014).
- 47 . New criteria for supplementation of selected micronutrients in the era of nutrigenetics and nutrigenomics. Int. J. Food Sci. Nutr. 65(5), 529–538 (2014).
- 48 Genetic testing registry (GTR). www.ncbi.nlm.nih.gov/gtr/all/tests/?term=all[sb].
- 49 . Epigenetics in clinical practice: characterizing patient and provider experiences with MTHFR polymorphisms and methylfolate. J. Nutrigenet. Nutrigenomics 8(3), 137–150 (2015).
- 50 Guide and position of the international society of nutrigenetics/nutrigenomics on personalised nutrition: part 1 – fields of precision nutrition. J. Nutrigenet. Nutrigenomics 9(1), 12–27 (2016). • An excellent review on the current state of knowledge in NGx and associated new fields of science.
- 51 . Moral responsibility for (un)healthy behaviour. J. Med. Ethics 39(11), 695–698 (2013).
- 52 . Role of genomics on the path to personalized medicine. Metabolism 62(Suppl. 1), S2–S5 (2013).
- 53 . Genetics and personal responsibility for health. New Genet. Soc. 33(2), 113–125 (2014). •• An excellent and accessible article that describes the complex ethical implications of genetics on personal responsibility.
- 54 . The good life: living for health and a life without risks? On a prominent script of nutrigenomics. Br. J. Nutr. 101(3), 307–316 (2009). • Describes the considerable mismatch between how food and health are conceptualized by NGx (where food is exclusively interpreted in terms of disease prevention) compared with society and individuals.
- 55 . Coevolution of nutrigenomics and society: ethical considerations. Am. J. Clin. Nutr. 94(6 Suppl), S2025–S2029 (2011).
- 56 . Ethical issues raised by personalized nutrition based on genetic information. Genes Nutr. 1(1), 13–22 (2006).
- 57 . Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition. Genes Nutr. 8(4), 373–381 (2013).
- 58 . Disclosure of genetic information and change in dietary intake: a randomized controlled trial. PLoS ONE 9(11), e112665 (2014).
- 59 . The effect of communicating the genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome: a systematic review and meta-analysis of randomised controlled trials. Br. J. Nutr. 116(5), 924–934 (2016).
- 60 . The role of genes in talking about overweight: an analysis of discourse on genetics, overweight and health risks in relation to nutrigenomics. Public Underst. Sci. 23(8), 886–902 (2014).
- 61 . I eat healthfully but I am not a freak. Consumers’ everyday life perspective on healthful eating. Appetite 53(3), 390–398 (2009).
- 62 . An insight into the public acceptance of nutrigenomic-based personalised nutrition. Nutr. Res. Rev. 26(1), 39–48 (2013).
- 63 . Using ApoE genotyping to promote healthy lifestyles in Finland – psychological impacts: randomized controlled trial. J. Genet. Couns. 24(6), 908–921 (2015). • There is a need for more research on the impact of personal genetic information on lifestyle behavior changes. This study assessed the psychological effects of personal genetic information, provided by different APOE genotypes, as a tool to promote such lifestyle changes.
- 64 Consumer perceptions of interactions with primary care providers after direct-to-consumer personal genomic testing. Ann. Intern. Med.
doi:10.7326/M15-0995 (2016) (Epub ahead of print). - 65 . Ethical issues in obesity interventions for populations. NSW Public Health Bull. 23(5–6), 116–119 (2012).
- 66 . Unintended consequences of obesity-targeted health policy. Virtual Mentor 15(4), 339–346 (2013).
- 67 . Ethical aspects of obesity prevention. Best Pract. Res. Clin. Gastroenterol. 28(2), 303–314 (2014).
- 68 . The genetic counselor's role in managing ethical dilemmas arising in the laboratory setting. J. Genet. Couns. 25(5), 838–854 (2016).
- 69 . Captious certainties: makings, meanings and misreadings of consumer-oriented genetic testing. J. Community Genet. 5(1), 81–87 (2014).
- 70 . Translating personalized medicine using new genetic technologies in clinical practice: the ethical issues. Per. Med. 11(2), 211–222 (2014).
- 71 . Genetic counseling practice in next generation sequencing research: implications for the ethical oversight of the informed consent process. J. Genet. Couns. 23(4), 661–670 (2014).
- 72 . The deceptive appeal of direct-to-consumer genetics. Ann. Intern. Med.
doi:10.7326/M16-0257 (2016) (Epub ahead of print). - 73 . Internet-based direct-to-consumer genetic testing: a systematic review. J. Med. Internet Res. 17(12), e279 (2015).
- 74 . The on-line promotion and sale of nutrigenomic services. Genet. Med. 10(11), 784–796 (2008).
- 75 . The challenge of implementing genetic tests with clinical utility while avoiding unsound applications. J. Community Genet. 5(1), 7–12 (2014).
- 76 Nutrigenomics – perspectives from registered dietitians: a report from the Quebec-wide e-consultation on nutrigenomics among registered dietitians. J. Hum. Nutr. Diet. 27(4), 391–400 (2014).
- 77 . Canadian health care professionals’ knowledge, attitudes and perceptions of nutritional genomics. Br. J. Nutr. 104(8), 1112–1119 (2010).
- 78 . Position of the academy of nutrition and dietetics: nutritional genomics. J. Acad. Nutr. Diet. 114(2), 299–312 (2014).
- 79 . Factors associated with the intention of registered dietitians to discuss nutrigenetics with their patients/clients. Can. J. Diet. Pract. Res.
doi:10.3148/cjdpr-2016-005 (2016) (Epub ahead of print). - 80 . Bioethical considerations for human nutrigenomics. Annu. Rev. Nutr. 28, 447–467 (2008).
- 81 Consumers on the Internet: ethical and legal aspects of commercialization of personalized nutrition. Genes Nutr. 8(4), 349–355 (2013).