{"id":9349,"date":"2026-04-07T14:20:32","date_gmt":"2026-04-07T14:20:32","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/maya-schulpen\/"},"modified":"2026-04-23T08:14:25","modified_gmt":"2026-04-23T08:14:25","slug":"maya-schulpen","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/maya-schulpen\/","title":{"rendered":"Maya Schulpen"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":13345,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-9349","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Mediterranean diet adherence and cancer risk in the Netherlands","samenvatting":"De ziekte kanker heeft vanwege haar hoge incidentie en sterfte een nadelige invloed op het leven van veel mensen. Naar schatting had ongeveer tien procent van de gediagnosticeerde kankers in Nederland in 2010 voorkomen kunnen worden door gezonde voeding. Het traditionele mediterraan dieet (MD) kan worden gedefinieerd als het voedingspatroon dat eind jaren \u201950, begin jaren \u201960 van de vorige eeuw kenmerkend was voor gebieden grenzend aan de Middellandse Zee waar olijven werden geteeld (Hoofdstuk 1). Het MD was een plantaardig dieet dat werd gekarakteriseerd door een hoge inname van groenten, fruit, peulvruchten, noten, volkoren graanproducten en olijfolie (een bron van enkelvoudig onverzadigde vetzuren). De inname van vlees en zuivelproducten was daarentegen laag. Alcohol werd geconsumeerd in matige hoeveelheden, met name gedurende de maaltijd.\n\nEr zijn meerdere gezondheidsvoordelen toegeschreven aan het MD, waaronder een verlaagde sterfte en een verlaagd risico op hart- en vaatziekten. Hoewel het mogelijk gunstige effect van het MD op het risico op kanker de afgelopen jaren in toenemende mate is onderzocht, is het huidige bewijs voor de meeste kankersoorten nog beperkt. Daarnaast waren de resultaten van onderzoeken niet altijd consistent en hadden veel studies een pati\u00ebntcontrole-opzet. Het pati\u00ebntcontrole-onderzoeksdesign is gevoelig voor bias, om welke reden cohortonderzoeken de voorkeur hebben. Tot slot verschilt het verband met het MD mogelijk tussen de geslachten en\/of subtypen van kankersoorten. Dit is echter zelden in prospectieve studies onderzocht. Het doel van dit proefschrift was daarom om het verband tussen naleving van het MD en incidentie van zowel kanker in het algemeen als verscheidene kankersoorten (i.c. long-, borst-, slokdarm-, maag-, alvleesklier-, colorectaal-, prostaat- en blaaskanker) in Nederland te onderzoeken in een prospectieve setting. Hierbij hebben we ook aandacht besteed aan mogelijke verschillen in associaties tussen mannen en vrouwen en subtypen van de onderzochte kankersoorten. De mate van naleving van het MD werd vastgesteld met behulp van twee a priori gedefinieerde MD-scores, namelijk de \u2018alternate Mediterranean diet score\u2019 (aMED) en de \u2018modified Mediterranean diet score\u2019 (mMED). Alcoholconsumptie is een risicofactor voor meerdere vormen van kanker. Daarom hebben we gereduceerde varianten van aMED en mMED gecre\u00eberd (respectievelijk aMEDr en mMEDr) waar alcoholconsumptie geen deel van uitmaakt. Vervolgens hebben we de \u2018performance\u2019 van modellen met gereduceerde (zonder alcohol) en originele (met alcohol) MD-scores vergeleken. Onder \u2018model performance\u2019 verstaan we de mate waarin een statistisch model de geobserveerde data verklaart. Voor ons onderzoek hebben we met name gebruik gemaakt van data van de 120.852 deelnemers van de Nederlandse Cohortstudie naar voeding en kanker (NLCS). Bij aanvang van deze studie in september 1986 waren de deelnemers tussen de 55 en 69 jaar oud. Om de statistische power te vergroten, hebben we de relatie tussen naleving van het MD en het risico op alvleesklierkanker onderzocht door resultaten van de NLCS en het Nederlandse cohort van de European Prospective Investigation into Cancer and Nutrition (EPIC-NL) samen te voegen. Het EPIC-NL cohort is gevormd tussen 1993 en 1997 en bestaat uit 40.011 mannen en vrouwen in de leeftijd van 20-70 jaar. NLCS-deelnemers zijn voor maximaal 20,3 jaar gevolgd voor het optreden van kanker. De mediane follow-up in EPIC-NL was 19,2 jaar.\n\nDe performance van de modellen was voor de meeste kankersoorten vergelijkbaar of beter wanneer de naleving van het MD werd vastgesteld met behulp van aMEDr dan wanneer dit was gebeurd met mMEDr. Daarom hebben we besloten dat aMEDr onze belangrijkste maat was in de bepaling van naleving van het MD. Tevens heeft de score variant zonder alcohol de voorkeur, omdat alcoholconsumptie een risicofactor is voor verscheidene kankersoorten. Hogere MD-scores (aMEDr) waren geassocieerd met een niet statistisch significant verlaagd risico op longkanker bij mannen en vrouwen (Hoofdstuk 2). De inverse verbanden leken het sterkst bij vrouwen en nooit-rokers. De sterkte van de associatie leek ook te vari\u00ebren tussen de histologische longkanker-subtypen, met name bij mannen. Heterogeniteitstesten waren echter niet statistisch significant.\n\nEen toename in aMEDr was ook geassocieerd met een niet statistisch significant verlaagde incidentie van postmenopauzale borstkanker bij vrouwelijke NLCS-deelnemers (Hoofdstuk 3). Stratificatie op basis van oestrogeenreceptor (ER) status liet zien dat het inverse verband sterker en enkel statistisch significant was voor het ER-negatieve subtype. We zagen een vergelijkbaar patroon voor de progesteronreceptor (PR) en gecombineerde ER\/PR subtypen. Tot slot hebben we de resultaten van de NLCS gecombineerd met resultaten van eerder gepubliceerde cohortstudies in random-effects meta-analyses. De resultaten van deze meta-analyses kwamen overeen met de NLCS-bevindingen. MD-scores were invers geassocieerd met het risico op postmenopauzale borstkanker, met name van het ER-negatieve subtype.\n\nSlokdarm- en maagkanker-subtypen, gedefinieerd op basis van respectievelijk histologie en anatomische locatie, verschillen mogelijk in etiologie. De relatie tussen naleving van het MD en het risico op slokdarm- en maagkanker-subtypen was het onderwerp van Hoofdstuk 4. Hogere MD-scores waren bij mannen geassocieerd met een significant verlaagd risico op plaveiselcelcarcinoom van de slokdarm (ESCC). aMEDr was echter niet geassocieerd met het risico op ESCC bij vrouwen of het risico op adenocarcinoom van de slokdarm (EAC) bij zowel mannen als vrouwen. Wat betreft de maagkanker-subtypen vonden we inverse verbanden tussen aMEDr en risico\u2019s op cardia en non-cardia adenocarcinoom van de maag (respectievelijk GCA en GNCA) bij beide geslachten. De gevonden verbanden waren echter alleen statistisch significant bij mannen.\n\nHet verband tussen naleving van het MD en het risico op alvleesklierkanker werd in Hoofdstuk 5 onderzocht met behulp van data verzameld in de NLCS en EPIC-NL cohorten. aMEDr was niet statistisch significant geassocieerd met het risico op microscopisch bevestigde alvleesklierkanker (MCPC) in gepoolde en cohort-specifieke analyses, ongeacht geslacht. Er was sprake van mogelijke effectmodificatie door rookstatus. Er leek een zwak en niet significant invers verband aanwezig te zijn bij nooit-rokers, terwijl hiervoor geen aanwijzingen waren bij onderzoeksdeelnemers die wel ooit hadden gerookt. De conclusie was vergelijkbaar wanneer ook niet-microscopisch bevestigde gevallen van alvleesklierkanker in de analyses werden meegenomen.\n\naMEDr was eveneens niet statistisch significant geassocieerd met het risico op colorectaalkanker (Hoofdstuk 6). Dit was het geval voor alle onderzochte anatomische subtypen (i.e. colon, proximale colon, distale colon en rectum) bij zowel mannen als vrouwen.\n\nIn Hoofdstuk 7 hebben we associaties tussen naleving van het MD en het risico op prostaat- en blaaskanker onderzocht. Associaties met prostaatkankerrisico zijn apart geschat voor \u2018advanced\u2019 (oftewel van een gevorderd stadium) en \u2018nonadvanced\u2019 tumoren op het moment van diagnose. Deze tumoren verschillen mogelijk in etiologie en risicofactoren. De subgroep van \u2018nonadvanced\u2019 prostaatkankers bestaat met name uit minder agressieve tumoren die mogelijk nooit een klinisch relevant stadium zullen bereiken. Daarom beschouwen we het risico op \u2018advanced\u2019 prostaatkanker als de belangrijkste uitkomstmaat. aMEDr was in onze analyses niet geassocieerd met het risico op \u2018advanced\u2019 prostaatkanker. Een statistisch significant positief verband werd echter gevonden voor \u2018nonadvanced\u2019 prostaatkanker. Hierbij moet worden opgemerkt dat mannen met een hoger opleidingsniveau en een gezondere leefstijl zich mogelijk meer bewust zijn van prostaatkanker en wellicht ook eerder gebruik zullen maken van de zorg en deel zullen nemen aan screeningsprogramma\u2019s. Daarom is het aannemelijk dat \u2018nonadvanced\u2019 prostaattumoren in dit deel van de populatie vaker gediagnosticeerd worden. Er was geen indicatie voor een associatie tussen aMEDr en het risico op blaaskanker. Onze bevindingen waren vergelijkbaar voor blaaskanker in het algemeen, invasieve blaaskanker en niet-invasieve blaaskanker. De effectschattingen voor blaaskanker werden gebaseerd op zowel mannen als vrouwen.\n\nDe relatie tussen naleving van het MD en het risico op kanker in het algemeen was de focus van Hoofdstuk 8. Hogere MD-scores waren geassocieerd met een niet significant verlaagd risico op kanker bij vrouwen. Er was echter geen sprake van een relatie bij mannen. Tevens hebben we kankersoorten ingedeeld in subgroepen op basis van de relatie met roken, obesitas en alcoholconsumptie. Associaties met aMEDr waren bij vrouwen voor de verschillende subgroepen vergelijkbaar. Ofschoon ook bij mannen de verschillen tussen de subgroepen klein en irrelevant leken, waren heterogeniteitstesten bij mannen significant voor alle vergelijkingen. Deze observatie kan wellicht worden verklaard door de hoge statistische power. Zoals eerder beschreven was in dit proefschrift aMEDr (zonder alcohol) de primaire maat voor vaststelling van naleving van het MD. Grotendeels vergelijkbare resultaten werden verkregen wanneer we de originele aMED (inclusief alcohol) gebruikten. De model performance was in de meeste gevallen echter vergelijkbaar of beter voor de MD-score variant zonder alcohol.\n\nIn Hoofdstuk 9 hebben we geprobeerd om de bevindingen van dit proefschrift in perspectief te plaatsen door deze te relateren aan resultaten van eerdere studies en door beschouwing van enkele methodologische aspecten. Daarnaast worden hier implicaties voor de volksgezondheid en aanbevelingen voor vervolgonderzoek behandeld.\n\nOp basis van dit proefschrift kunnen we concluderen dat naleving van het MD mogelijk verband houdt met een verlaagd risico op verschillende kanker(sub)typen in Nederland. Het MD zou daarom wellicht een interessante voedingsstrategie zijn voor de preventie van kanker in de Nederlandse samenleving. Het huidige bewijs volstaat echter nog niet voor de formulering van definitieve conclusies omtrent het mogelijk risicoverlagend effect van het MD op kanker. De inverse verbanden die we in dit proefschrift vonden, waren niet altijd statistisch significant en het aantal prospectieve cohortstudies is voor sommige kanker(sub)typen nog steeds beperkt. Zowel onze bevindingen als de literatuur wekken de indruk dat associaties met naleving van het MD mogelijk verschillen tussen de geslachten en\/of afhankelijk zijn van het kankersubtype dat wordt onderzocht. Onderzoeksresultaten worden in studies helaas nog lang niet altijd gespecificeerd naar geslacht en subtype. Toekomstige goed uitgevoerde cohort- en interventiestudies kunnen wellicht het bewijs leveren dat noodzakelijk is om de promotie van het MD in het licht van kankerpreventie te rechtvaardigen. Totdat dit daadwerkelijk het geval is kunnen beleidsmakers in Nederland overwegen om het MD als uitgangspunt te nemen voor de ontwikkeling van een gezond plantaardig voedingspatroon gericht op de preventie van chronische ziekten in het algemeen.\n\nValorization\n\nThe term \u201cvalorization\u201d refers to the process of creating societal or economic value from scientific knowledge. In addition to education and research, valorization by law constitutes the third core task of Dutch universities. In this section, we will discuss how our key findings with regard to the potential cancer-protective effect of the Mediterranean diet (MD) in a non-Mediterranean population can be of significance to society apart from their scientific value through publication in impact journals.\n\nBefore elaborating on the valorization potential of our findings, we will first briefly introduce the concept of the MD and its key components. In this thesis, the traditional MD was defined as \u201cthe dietary pattern typical of the Mediterranean regions traditionally known for olive cultivation in the late 1950s and the early 1960s\u201d. Consumption of plant foods (e.g., vegetables, fruits, legumes, nuts, and whole grains) was abundant in this dietary pattern, whereas the intake of animal foods (e.g., meat and dairy) was limited. Other characteristics of the traditional MD were the high ratio of monounsaturated to saturated fatty acids resulting from the generous consumption of olive oil and a moderate consumption of alcohol during meals [1, 2].\n\nA considerable part of cancer cases is presumably preventable with healthy dietary habits. For the Dutch population, it has been estimated that approximately 10% of cancer diagnoses in 2010 could be ascribed to a less than optimal diet [3]. Society could benefit from nutritional research through the translation of results into dietary guidelines. For example, the World Cancer Research Fund\/American Institute for Cancer Research (WCRF\/ AICR) has formulated nine recommendations for cancer prevention in their Third Expert Report in 2018 [4] after systematic review of the scientific literature focusing on the relation of diet, nutrition, and physical activity to cancer. According to the Expert Panel, the evidence with respect to a \u201cMediterranean type\u201d dietary pattern was still inadequate to allow a meaningful recommendation. The findings of this thesis may be included in possible future Expert Reports of the WCRF\/AICR and in this way contribute to the formulation of international lifestyle guidelines for cancer prevention.\n\nRegarding the potential of the MD as a dietary strategy specifically aimed at cancer prevention, our results suggested that in the Netherlands, MD adherence may be associated with reduced risks of cancers of the lung, female breast (postmenopausal), esophagus (squamous cell carcinoma in men), and stomach. The prognosis of most of these cancer sites is relatively poor, stressing the importance of preventive strategies. However, as already discussed in Chapter 9 of this thesis, the currently available evidence does probably not suffice to recommend Dutch policymakers to promote the MD specifically for cancer prevention at this time.\n\nIn addition to its potentially favorable effect on cancer risk, MD adherence may be associated with various other health benefits, including reduced mortality and lower risks of several chronic diseases. This enables the formulation of a clear, consistent (with respect to disease risk) message to society and is likely to enhance the usability of the MD as a dietary strategy to improve the health status of the population. Furthermore, the MD is generally considered a palatable dietary pattern with a relatively low impact on the environment. Policymakers in the Netherlands could possibly use the MD as a framework to develop a healthy plant-based dietary pattern with the purpose of preventing chronic disease in general (see Chapter 9 for a more elaborate discussion).\n\nThe successful implementation of a healthy plant-oriented dietary pattern in the Dutch population most likely requires an integrative approach involving organized efforts of the government and society as a whole [4]. Policies are warranted that enable and encourage the adoption of the promoted dietary pattern by the community. In order to achieve these aims, such policy actions should influence the three domains of food environment, food system, and behavior change communication [4]. The behavior change domain encompasses educating people about health effects of food and nutrition by raising public awareness [4]. In this respect, (inter)national media attention has been paid to the health benefits of the MD in recent years. For example, our scientific article concerning MD adherence and postmenopausal breast cancer risk has been highlighted on (inter)national news websites. In addition to \u201cunregulated\u201d media attention, which is often concentrated on recent research papers showing positive health effects of MD adherence, Dutch authorities could play a role in promoting and disseminating a MD-derived plant-oriented dietary pattern in a more organized manner. In this instance, the Health Council of the Netherlands (\u201cGezondheidsraad\u201d) and the Netherlands Nutrition Centre (\u201cVoedingscentrum\u201d) could get involved. Over the past decades, the Health Council of the Netherlands has issued several recommendations for a healthy dietary pattern targeted at the general Dutch population, with the most recent update being published in 2015 [5]. The Dutch dietary guidelines 2015 [5] were formulated by taking the latest scientific evidence concerning chronic disease risk into consideration and integrate information regarding nutrients, foods, and dietary patterns. According to the Dutch dietary guidelines 2015, recommended dietary patterns (including the traditional MD) characterized by a higher consumption of plant foods and a lower consumption of foods from animal origin, positively affect health [5]. The Netherlands Nutrition Centre is a leading authority that is committed to advising the public and health care professionals about healthy and more sustainable dietary habits and aims to encourage people to change their current eating habits accordingly [6]. The Netherlands Nutrition Centre has created the \u201cWheel of Five\u201d (\u201cSchijf van Vijf\u201d) [5-7]. The \u201cWheel of Five\u201d 2016 is a practical translation of the Dutch dietary guidelines 2015 for use in nutritional counseling, which has been complemented with specific recommendations in order to make sure that people meet their energy and nutrient requirements. Activities of the Netherlands Nutrition Centre promoting the dissemination of the \u201cWheel of Five\u201d by health care professionals include educating this group about the \u201cWheel of Five\u201d and its components in general, as well as its development and expected health benefits. Furthermore, information, materials, and tools (e.g., leaflets, posters, and explanatory videos) are provided to support the use of the \u201cWheel of Five\u201d in clinical practice. For the general population, the website of the Netherlands Nutrition Centre contains a wealth of information and tools to help and encourage individuals to make healthier food choices. Along with a description of the \u201cWheel of Five\u201d, the website features advice, recipes, daily meal plans, and e-tools (e.g., \u201cSchijf van Vijf voor jou\u201d and \u201cMijn eet-update\u201d) to inspire people [6, 7].\n\nIn addition to the actions suggested above, informative presentations concerning the potential health benefits of the MD could be given at conferences for health care professionals, who could in turn transfer this knowledge to patients via nutritional counseling.\n\nWhen confirmed, the findings of this thesis could contribute to a decrease in morbidity and mortality due to cancer (and possibly other chronic diseases) in the Netherlands through the formulation of dietary guidelines and an increased public awareness of the impact of diet and other lifestyle factors on people\u2019s health. Interestingly, increasing adherence to the MD seemed to be especially associated with reduced risks of cancers with a relatively poor prognosis. In addition to a reduced social burden, the prevention of cancer may have economic benefits, such as decreased health care costs and a reduced loss of productivity at the workplace. Finally, adoption of a Mediterranean(-like) dietary pattern by the Dutch population is likely to have advantageous effects for the environment as well [8-13]. A study by Van Dooren et al. [11] compared greenhouse gas emissions and land use associated with six dietary patterns, including the average Dutch diet of 1998 and the MD, in female adults. Greenhouse gas emissions and land use for the MD were estimated to be clearly lower than for the average Dutch diet [11], which underscores the benefits of adopting a Mediterranean(-like) dietary pattern.","summary":"With its high incidence and mortality, cancer negatively affects many lives. According to estimations, about a tenth of the cancers diagnosed in the Netherlands in 2010 would have been preventable by the adoption of a healthy diet. The traditional Mediterranean diet (MD) can be defined as the dietary pattern typical of the olive-cultivating areas bordering the Mediterranean Sea in the late 1950s and the early 1960s, which was primarily based on plant foods (Chapter 1). The MD was characterized by a high consumption of vegetables, fruits, legumes, nuts, whole grains, and olive oil (rich in monounsaturated fatty acids). In contrast, the intake of meat and dairy products was low. Alcohol was consumed in moderate amounts and usually during meals. Adherence to the MD has been associated with numerous health benefits, including reduced all-cause mortality, and cardiovascular disease incidence and mortality. Despite the increasing interest in the potential cancer-protective effect of MD adherence in recent years, the evidence is still limited for most cancer sites. Additionally, results of conducted studies were not always consistent and had often been obtained using case-control designs, which are prone to bias. Moreover, potential heterogeneity of associations with MD adherence across the sexes or subtypes of specific cancer sites has been suggested, but has rarely been evaluated in prospective studies. Therefore, the principal aim of this thesis was to prospectively evaluate the association of MD adherence with incidence of specific cancer sites (i.e., lung, breast, esophagus, stomach, pancreas, colorectum, prostate, and bladder) as well as overall cancer incidence in the Netherlands. Specific attention was paid to possible differences in associations between men and women, and across subtypes of the investigated cancer sites. The relative level of MD adherence was assessed using two a priori defined MD scores, namely the alternate Mediterranean diet score (aMED) and the modified Mediterranean diet score (mMED). Alcohol consumption may increase the risk of multiple types of cancer even at low or moderate intake levels. Therefore, reduced variants of aMED and mMED were created that did not include the alcohol component (aMEDr and mMEDr, respectively) and models containing MD score variants with and without alcohol were compared in terms of performance. In order to investigate our aims, we primarily used data collected from the 120852 participants of the population-based Netherlands Cohort Study on Diet and Cancer (NLCS), who were between the ages of 55 and 69 years at baseline in September 1986. To increase statistical power, the association between MD adherence and pancreatic cancer risk was evaluated by pooling results from the NLCS and the Dutch cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-NL). The EPIC-NL cohort includes 40011 men and women, who were aged 20 to 70 years at enrolment between 1993 and 1997. NLCS participants were followed up for cancer incidence for a maximum of 20.3 years, whereas the median follow-up in EPIC-NL was 19.2 years.\n\nFor the majority of the cancer sites, aMEDr-containing models had an equal or better performance than mMEDr-containing models. Therefore, aMEDr was considered our principal measure of MD adherence. Furthermore, the score variant without alcohol component was preferred, because of the carcinogenic effect of alcohol in humans. Higher MD adherence (aMEDr) was associated with a non-significantly reduced lung cancer risk in men and women (Chapter 2). Subgroup analyses suggested that the non-significant inverse association was most pronounced in women and those who never smoked, but the interaction tests did not reach statistical significance. When comparing associations with aMEDr across the histological lung cancer subtypes, some variations in strength were observed, especially in men.\n\nIncreasing levels of MD adherence were also associated with a non-significantly reduced incidence of postmenopausal breast cancer in female NLCS participants (Chapter 3). Stratification by estrogen receptor (ER) status showed that the inverse association was strongest and only statistically significant for the ER negative subtype. Similar findings were obtained when we evaluated progesterone receptor (PR) and combined ER\/PR subtypes. Finally, we combined our results of the NLCS and results of previously published cohort studies in random-effects meta-analyses. Results of these meta-analyses were in line with the NLCS observations, showing inverse associations between MD adherence and postmenopausal breast cancer risk, particularly of the ER negative subtype.\n\nFor esophageal and gastric cancer (Chapter 4), associations with MD adherence were evaluated separately for subtypes defined by histology and anatomic location, respectively, which were suggested to have distinct etiological backgrounds. A significantly decreased risk of esophageal squamous cell carcinoma (ESCC) was observed among men with higher levels of MD adherence. In contrast, MD adherence was not associated with ESCC risk in women or risk of esophageal adenocarcinoma (EAC) in both men and women. Although statistical significance was only reached in men, MD adherence was inversely associated with risks of gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in both sexes.\n\nUsing data of both the NLCS and EPIC-NL cohorts, the relation of MD adherence with pancreatic cancer incidence was investigated in Chapter 5. MD adherence was not significantly associated with the risk of microscopically confirmed pancreatic cancer (MCPC) in pooled and cohort-specific analyses, irrespective of sex. Potential effect modification by smoking status was indicated. MD adherence was weakly and non-significantly inversely associated with MCPC risk in never smokers, but not in ever smokers. The overall conclusion did not change when we also included cases who were not microscopically confirmed in the analyses.\n\nFurthermore, MD adherence was not significantly associated with colorectal cancer risk in men and women, regardless of the anatomical subsite (i.e., colon, proximal colon, distal colon, and rectum) evaluated (Chapter 6).\n\nAssociations of MD adherence with risks of prostate and bladder cancer were examined in Chapter 7. For prostate cancer, associations were estimated separately for advanced and nonadvanced tumors at diagnosis, because differences in etiology and risk factor profiles have been suggested. The subgroup of nonadvanced prostate cancers at diagnosis mainly encompasses less aggressive tumors, which progress slowly and might never become clinically relevant. Therefore, we considered advanced prostate cancer risk to be the most interesting outcome. MD adherence was not associated with advanced prostate cancer risk in our analyses. For nonadvanced prostate cancer risk, a statistically significant positive association was observed. The prostate cancer awareness, likelihood to seek care, and screening attendance may be higher among well-educated men with healthier lifestyles and higher MD adherence. Consequently, nonadvanced prostate tumors may more commonly be diagnosed in this part of the population. Additionally, we evaluated the association between MD adherence and bladder cancer risk combining male and female NLCS participants, and showed that there was no evidence of a relation, irrespective of the malignancy grade at diagnosis.\n\nThe association of MD adherence with overall cancer incidence was the focus of Chapter 8. Higher MD adherence was associated with a non-significantly reduced cancer risk in women, but not in men. In women, similar associations with MD adherence were observed for subgroups of cancers related vs. not related to tobacco smoking, obesity, and alcohol consumption. Even though differences across the subgroups seemed small and irrelevant in men as well, heterogeneity tests in men were significant for all subgroup comparisons made, possibly because of the high statistical power.\n\nAs was described above, our primary measure of MD adherence was aMEDr, which does not include the alcohol component. Largely similar results were obtained when MD adherence was assessed using the original aMED including the alcohol component. However, in most cases an equal or better model performance was observed for the MD score variant without alcohol.\n\nIn Chapter 9, the findings of this thesis were put into perspective by relating them to results of previously published studies and discussing methodological considerations. Moreover, implications for public health and recommendations for future research were addressed. This thesis shows that higher MD adherence might be associated with a reduced risk of several cancer (sub)types in the Netherlands. Therefore, the MD could potentially be an interesting dietary approach in the prevention of cancer in the Dutch population. However, when looking at the totality of the evidence, no final conclusions regarding the cancer-preventive properties of the MD can be drawn at this time. Inverse associations in our analyses did not always reach statistical significance and the number of prospective cohort studies is still small for some cancer (sub)sites. In agreement with our findings, it has been suggested that associations with MD adherence might differ between the sexes and\/or depend on the cancer subsite evaluated, but unfortunately, it is not common practice yet to report sex- and subtype-specific results. Accordingly, in future, well-designed cohort studies and randomized controlled trials are warranted, which might provide the additional evidence required to justify the promotion of the MD with the specific aim to prevent cancer. Until this is the case, policymakers in the Netherlands could consider using the MD as a framework to develop a healthy plant-based dietary strategy for the prevention of chronic diseases in general.","auteur":"Maya Schulpen","auteur_slug":"maya-schulpen","publicatiedatum":"9 juli 2020","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/mayaschulpen?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604071416","isbn":"978-94-6380-802-6","doi_nummer":"","naam_universiteit":"Universiteit Maastricht","afbeeldingen":13345,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit Maastricht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9349","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=9349"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9349\/revisions"}],"predecessor-version":[{"id":9352,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9349\/revisions\/9352"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/13345"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=9349"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=9349"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}