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bioética y nutrigenómica 2008 (23)

bioética y nutrigenómica 2008 (23)

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Bioethical Considerationsfor Human Nutrigenomics
 Manuela M. Bergmann,
Ulf G ¨orman,
and John C. Mathers
Department of Epidemiology, German Institute of Human Nutrition,Potsdam-Rehbr ¨ucke, D-14558 Germany; email: bergmann@dife.de
Department of Ethics, Lund University, SE-221 00 Lund, Sweden;email: ulf.gorman@teol.lu.se
Human Nutrition Research Center, Newcastle University, Newcastle upon Tyne,NE2 4HH United Kingdom; email: john.mathers@ncl.ac.uk  Annu. Rev. Nutr. 2008.28:447–67First published online as a Review in Advance on April 25, 2008 The
Annual Review of Nutrition
is online atnutr.annualreviews.org This article’s doi:10.1146/annurev.nutr.28.061807.155344Copyrightc
2008 by Annual Reviews. All rights reserved0199-9885/08/0821-0447$20.00
Key Words
ethics, nutrigenomics, human studies, personalized nutrition
 This article gives an overview of the ethical issues in nutrigenomics re-searchandpersonalizednutrition.Theprinciplesofresearchethics,i.e.,autonomy, beneficence, nonmalfeasance, and justice, are challenged by rapidly growing cross-border research activities utilizing existing andupcoming biobanks for studies of the interaction of genes with dieton risk of common diseases. We highlight the ethical issues, some un-resolved, in international collaborative projects of which researchersshould be aware. Personalized nutrition (tailoring diet on the basis of genotype) is one possible application of nutrigenomics research. How-ever, until the scientific evidence concerning diet–gene interactions ismuch more robust, the provision of personalized dietary advice on thebasis of specific genotype remains questionable. From the ethical andsocialperspective,nutrigenomicsofferssignificantopportunitiestoim-prove public health by enhancing understanding of the mechanismsthroughwhichdietcanbeusedtoreducetheriskofcommonpolygenicdiseases.
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deoxyribonucleic acid
NUTRIGENOMICS—INTRODUCTION TO THE CONCEPT ................. 448HUMAN NUTRIGENOMICSRESEARCH—ETHICALCONSIDERATIONS ............. 450Underlying Ethical Principles ...... 450New Ethical Principles for a NewField in Nutritional Science? .... 450Informed Consentfor Genomic Research .......... 450Benets and Risks.................. 451Biobanks in Nutrigenomics......... 452 What Do ResearchParticipants Think?............. 454PERSONALIZEDNUTRITION—ETHICAL AND SOCIAL IMPLICATIONS .. 455 The Idea of PersonalizedNutrition....................... 455Observance........................ 456Public Expectationsfrom Personalized Nutrition..... 456Food, Health, and Well-Being...... 456“The Unhealthy Quest forHealth........................ 456 The Role of Genetic Testing ....... 457Genetic Counseling in Connectionto Personalized Nutrition ....... 457 Tests Directly Sold to the Public.... 458Individual or Population Approach?...................... 459Products Fabricatedfor Personalized Nutrition ...... 459 Justice Questions .................. 460CONCLUSIONS .................... 460
 Although it has been known for decadesthat certain nutrients can modify gene ex-pression (78), high-throughput, postgenomictechnologies—which twenty-first-century ad- vanceshavemadeavailableforstudyinginterac-tions between nutrition and the genome—havethe potential to revolutionize the understand-ingoflinksbetweenfoodandhealth.Thisistheniche occupied by the emergent science of nu-tritionalgenomics(nutrigenomics),whichaimsto reveal the intimate inter-relationships be-tween nutrition and the genome and to providethe scientific basis for improved public healththrough dietary means. Asillustratedin
,individualgeneticmakeup influences nutritional needs and may modify dietary choices (111). In addition, thenature and amounts of foods influence gene ex-pression at all levels of regulation, including viaalteredepigenomicmarkings(56).Genome- wide association studies are producing power-ful evidence for links between (novel) geneticloci and risk of common human diseases (103,121). However, since diet and other lifestylefactors are major determinants of these samediseases (125), it is highly likely that interac-tions between genotype and diet are impor-tant in determining the risk of most (if not all)common complex diseases. Proof of principlefor this hypothesis has been provided by obser- vational nutritional genetics studies where theoutcome measures have been markers of dis-ease risk, most notably cardiovascular disease(91). However, deoxyribonucleic acid (DNA)(andotherbiologicalmaterial)inbiobanksfromcohort (and other) studies investigating rela-tionships between dietary exposure and healthoutcomes provides a rich resource for novelstudies of diet–gene interactions (72). Suchstudies are particularly powerful when thestudies are large, dietary exposure (and otherlifestyle factors) is characterized robustly, andthere are hard end points such as diagnosis of disease or death from known causes. This hasencouraged the development of consortia thatcross national and continental borders to facil-itate the pooling of resources, including bio-logical samples and data as exemplified by theNational Cancer Institute Breast and ProstateCancer Cohort Consortium (22). To date, most studies have been relatively small scale, have focused on individual genes
 448 Bergmann
G¨ orman
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Figure 1
Conceptual model of interactions between nutrition and the genome underlying links between food and health. The science of nutrigenomics uses high throughput, postgenomics technologies to investigate these interactions.
(or haplotypes) and single nutrients, and havenot addressed the complexity inherent in in-teractions between multiple genetic and mul-tiple dietary factors (77). To determine causal-ity,anextensiveprogramofhumaninterventionstudies is needed, and its design should includeprospective genotyping of volunteers (82) tomaximize the likelihood of obtaining unequiv-ocal results.Until recently, much of the applicationof postgenomic technologies to understand-ing mechanistic interactions between nutritionand cell or tissue function and health has beendevoted to studies in cells or model organ-isms. Given the costs of some of these tech-nologies, the need to build expertise in theiruse, and the greater practical difficulties of hu-man studies, this prioritization is understand-able. However, over the past couple of yearsthere has been a welcome emergence of nu-trigenomics studies undertaken in human vol-unteers. Eady et al. (27) investigated the extentof, and factors responsible for, intra- and in-terindividual variation in transcription profilesfor approximately 14,000 genes in peripheralblood mononuclear cells; this work providesimportant information for the design of futurestudies. In an examination of responses to eat-ing breakfast (which included acetaminophen), van Erk et al. (114) observed 954 differentially expressed genes in blood, with approximately three times as many genes differentially ex-pressed after a high-protein meal than after ahigh-carbohydrate meal. Obtaining samples of tissue other than blood cells is often an im-pediment in human studies, but Polley et al.(93) demonstrated that it is possible to investi-gatetheproteomeofthehumancolorectalmu-cosa using biopsy samples and to identify po-tential novel biomarkers of bowel cancer risk.In principle, metabolomic studies on easily ac-cessiblebiofluids(e.g.,plasma,urine,andsaliva)couldbeincorporatedreadilyintoconventionalnutrition study designs and so provide an op-portunity to investigate the effect of the nutri-tional regime on a wide range of metabolites;such studies could greatlyenhance understand-ing of the impact of the intervention. Walshet al. (116) reported considerable inter- andintraindividual variation in metabolite profilesand concluded that the urinary metabolomeprovided a much better reflection of acute foodintake than did plasma or saliva. There is now significant international mo-mentum behind the development and exploita-tion of nutrigenomics approaches for both
Ethics of Nutrigenomics 449
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