Food groups, diet quality and colorectal cancer risk in the Basque Country

World Journal of Gastroenterology ISSN 1007-9327 (print) ISSN 2219-2840 (online) World J Gastroenterol 2020 July 28; 26(28): 3998-4181 Published by Baishideng Publishing Group Inc WJG https://www.wjgnet.com IJuly 28, 2020 Volume 26 Issue 28 World Journal of Gastroenterology W J G Contents Weekly Volume 26 Number 28 July 28, 2020 REVIEW Secondary causes of inflammatory bowel diseases 3998 Ghouri YA, Tahan V, Shen B Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis preand posttransplant: A multi-system challenge 4018 Steggerda JA, Mahendraraj K, Todo T, Noureddin M Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations 4036 Mpilla GB, Philip PA, El-Rayes B, Azmi AS Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease 4055 Cordes F, Foell D, Ding JN, Varga G, Bettenworth D MINIREVIEWS Helicobacter pylori infection: Beyond gastric manifestations 4076 Santos MLC, de Brito BB, da Silva FAF, Sampaio MM, Marques HS, Oliveira e Silva N, de Magalhães Queiroz DM, de Melo FF ORIGINAL ARTICLE Basic Study Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamideinduced cirrhotic rats 4094 Su W, Tai Y, Tang SH, Ye YT, Zhao C, Gao JH, Tuo BG, Tang CW Case Control Study Food groups, diet quality and colorectal cancer risk in the Basque Country 4108 Alegria-Lertxundi I, Aguirre C, Bujanda L, Fernández FJ, Polo F, Ordovás JM, Etxezarraga MC, Zabalza I, Larzabal M, Portillo I, de Pancorbo MM, Garcia-Etxebarria K, Rocandio AM, Arroyo-Izaga M Retrospective Study Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation 4126 Aranake-Chrisinger J, Dassopoulos T, Yan Y, Nalbantoglu I Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression 4140 Lomperta K, Jakubowska K, Grudzinska M, Kanczuga-Koda L, Wincewicz A, Surmacz E, Sulkowski S, Koda M WJG https://www.wjgnet.com II July 28, 2020 Volume 26 Issue 28 World Journal of Gastroenterology Contents Weekly Volume 26 Number 28 July 28, 2020 Enhancement parameters of contrast-enhanced computed tomography for pancreatic ductal adenocarcinoma: Correlation with pathologic grading 4151 Seo W, Kim YC, Min SJ, Lee SM Observational Study Detection of reflux-symptom association in children with esophageal atresia by video-pH-impedance study 4159 Maholarnkij S, Sanpavat A, Decharun K, Dumrisilp T, Tubjareon C, Kanghom B, Patcharatrakul T, Chaijitraruch N, Chongsrisawat V, Sintusek P Randomized Controlled Trial Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules 4170 Wen YD, Lu F, Zhao YP, Wang P, Yang Q, Li JX, Li HZ, Chi LL, Zhou ZH, Tang YP, Xu JK, Zhao Y, Tang XD WJG https://www.wjgnet.com III July 28, 2020 Volume 26 Issue 28 World Journal of Gastroenterology Contents Weekly Volume 26 Number 28 July 28, 2020 ABOUT COVER Editorial board member of World Journal of Gastroenterology, Dr. Osamu Toyoshima is a Director of Toyoshima Endoscopy Clinic in Tokyo, Japan. Dr. Toyoshima graduated from the University of Tokyo with his master´s degree in Medicine. After graduating, he joined the Department of Gastroenterology and Surgical Oncology at the University of Tokyo Hospital and engaged in clinical practice and medical research. After that, he established the Toyoshima Endoscopy Clinic with his father, Dr. Hiroshi Toyoshima. Toyoshima Endoscopy Clinic is an endoscopy-specialized clinic, which performs 10000 endoscopies annually. Dr. Osamu Toyoshima mainly conducts research using clinical data from Toyoshima Endoscopy Clinic. He is an expert in the field of gastroenterology, especially of gastric cancer risk evaluation based on the endoscopic gastritis and of quality indicators of colonoscopy such as colorectal polyp detection. AIMS AND SCOPE The primary aim of World Journal of Gastroenterology (WJG, World J Gastroenterol) is to provide scholars and readers from various fields of gastroenterology and hepatology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online. WJG mainly publishes articles reporting research results and findings obtained in the field of gastroenterology and hepatology and covering a wide range of topics including gastroenterology, hepatology, gastrointestinal endoscopy, gastrointestinal surgery, gastrointestinal oncology, and pediatric gastroenterology. INDEXING/ABSTRACTING The WJG is now indexed in Current Contents®/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch®), Journal Citation Reports®, Index Medicus, MEDLINE, PubMed, PubMed Central, and Scopus. The 2020 edition of Journal Citation Report® cites the 2019 impact factor (IF) for WJG as 3.665; IF without journal self cites: 3.534; 5-year IF: 4.048; Ranking: 35 among 88 journals in gastroenterology and hepatology; and Quartile category: Q2. RESPONSIBLE EDITORS FOR THIS ISSUE Electronic Editor: Yan-Liang Zhang; Production Department Director: Yun-Xiaojian Wu; Editorial Office Director: Ze-Mao Gong. NAME OF JOURNAL INSTRUCTIONS TO AUTHORS World Journal of Gastroenterology https://www.wjgnet.com/bpg/gerinfo/204 ISSN GUIDELINES FOR ETHICS DOCUMENTS ISSN 1007-9327 (print) ISSN 2219-2840 (online) https://www.wjgnet.com/bpg/GerInfo/287 LAUNCH DATE GUIDELINES FOR NON-NATIVE SPEAKERS OF ENGLISH October 1, 1995 https://www.wjgnet.com/bpg/gerinfo/240 FREQUENCY PUBLICATION ETHICS Weekly https://www.wjgnet.com/bpg/GerInfo/288 EDITORS-IN-CHIEF PUBLICATION MISCONDUCT Andrzej S Tarnawski, Subrata Ghosh https://www.wjgnet.com/bpg/gerinfo/208 EDITORIAL BOARD MEMBERS ARTICLE PROCESSING CHARGE http://www.wjgnet.com/1007-9327/editorialboard.htm https://www.wjgnet.com/bpg/gerinfo/242 PUBLICATION DATE STEPS FOR SUBMITTING MANUSCRIPTS July 28, 2020 https://www.wjgnet.com/bpg/GerInfo/239 COPYRIGHT ONLINE SUBMISSION © 2020 Baishideng Publishing Group Inc https://www.f6publishing.com © 2020 Baishideng Publishing Group Inc. All rights reserved. 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA E-mail: [email protected] https://www.wjgnet.com WJG https://www.wjgnet.com 4108 July 28, 2020 Volume 26 Issue 28 World Journal of Gastroenterology W J G Submit a Manuscript: https://www.f6publishing.com World J Gastroenterol 2020 July 28; 26(28): 4108-4125 DOI: 10.3748/wjg.v26.i28.4108 ISSN 1007-9327 (print) ISSN 2219-2840 (online) ORIGINAL ARTICLE Case Control Study Food groups, diet quality and colorectal cancer risk in the Basque Country Iker Alegria-Lertxundi, Carmelo Aguirre, Luis Bujanda, Francisco J Fernández, Francisco Polo, José Mª Ordovás, Mª Carmen Etxezarraga, Iñaki Zabalza, Mikel Larzabal, Isabel Portillo, Marian M de Pancorbo, Koldo Garcia-Etxebarria, Ana Mª Rocandio, Marta Arroyo-Izaga ORCID number: Iker AlegriaLertxundi 0000-0002-6702-9209; Carmelo Aguirre 0000-0003-35551550; Luis Bujanda 0000-0002-43539968; Francisco J Fernández 00000002-2230-2806; Francisco Polo 0000-0003-3305-1210; José Mª Ordovás 0000-0002-7581-5680; Mª Carmen Etxezarraga 0000-0002-49609429; Iñaki Zabalza 0000-0001-78924447; Isabel Portillo 0000-0002-38713423; Marian M de Pancorbo 00000002-8081-0702; Koldo GarciaEtxebarria 0000-0002-6107-9416; Ana Mª Rocandio 0000-0002-7803-8039; Marta Arroyo-Izaga 0000-0001-55924241. Author contributions: Arroyo-Izaga M, de Pancorbo MM, Aguirre C, Alegria-Lertxundi I, Bujanda L, Fernández FJ, Polo F, Etxezarraga MC, Zabalza I, Larzabal M, Rocandio AM, Garcia-Etxebarria K and Portillo I contributed to the conception, design and data acquisition; Arroyo-Izaga M, Alegria-Lertxundi I and Ordovás JM analysed the data, interpreted the results, and drafted the manuscript; and all the authors critically revised the paper and approved the final version of the manuscript. Supported by the Department of Health and Consumer Affairs, Iker Alegria-Lertxundi, Marta Arroyo-Izaga, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz 01006, Spain Carmelo Aguirre, Pharmacovigilance Unit, Galdakao-Usansolo University Hospital, Osakidetza, Galdakao 48960, Spain Luis Bujanda, Department of Gastroenterology, Donostia University Hospital / Biodonostia, University of the Basque Country UPV/EHU, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastian 20014, Spain Francisco J Fernández, Department of Gastroenterology, Galdakao-Usansolo University Hospital, Osakidetza, Galdakao 48960, Spain Francisco Polo, Department of Gastroenterology, Basurto University Hospital, Osakidetza, Bilbao 48013, Spain José Mª Ordovás, Nutrition and Genomics Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, United States of America; IMDEA Food, Madrid 28049, Spain Mª Carmen Etxezarraga, Department of Pathology, Basurto University Hospital, Osakidetza, Bilbao 48013, Spain; Department of Physician and Surgeon Specialities, University of the Basque Country UPV/EHU, Leioa 48940, Spain Iñaki Zabalza, Department of Pathology, Galdakao-Usansolo University Hospital, Osakidetza, Galdakao 48960, Spain Mikel Larzabal, Department of Pathology, Donostia Hospital / Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastian 20014, Spain Isabel Portillo, Colorectal cancer screening programme, Osakidetza, Bilbao 48011, Spain Marian M de Pancorbo, Ana Mª Rocandio, BIOMICs Research Group, University of the Basque Country UPV/EHU, Vitoria-Gasteiz 01006, Spain Koldo Garcia-Etxebarria, Biodonostia, Gastrointestinal genetics group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastian 20014, Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4109 July 28, 2020 Volume 26 Issue 28 Basque Government, No. 2011111153; Saiotek, Basque Government, No. S-PE12UN058; Pre-doctoral grant from the Basque Government, No. PRE_2015_2_0084; and United States Department of Agriculture— Agricultural Research Service, No. 58-1950-4-003. Institutional review board statement: This study was approved by the Clinical Research Ethics Committee of the Basque Country (reference numbers PI2011006 and PI2014042). Informed consent statement: Written informed consent was obtained from all the study participants. Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Data sharing statement: Dataset available from the corresponding author at [email protected]. STROBE statement: The authors have read the STROBE Statementchecklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items. Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: htt p://creativecommons.org/licenses /by-nc/4.0/ Manuscript source: Invited manuscript Received: February 28, 2020 Peer-review started: February 28, Spain Corresponding author: Marta Arroyo-Izaga, PharmD, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad, No. 7, Vitoria-Gasteiz 01006, Spain. [email protected] Abstract BACKGROUND The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations. AIM To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). METHODS This observational study included 308 patients diagnosed with CRC and 308 ageand sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. RESULTS The adjusted models for potential confounding factors showed a direct association between milk and dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR third tertile vs first tertile = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR third tertile vs first tertile = 0.40, 95%CI: 0.20-0.80). CONCLUSION Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern. Key words: Colorectal cancer; Food group; Dietary quality; Mediterranean diet; Riskfactors; Case-control study ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. Core tip: This matched case-control study supports the role of diet in colorectal cancer (CRC) risk. The results suggest that high consumption of high-fat cheeses is associated with CRC risk, whereas, a high intake of fiber-containing foods, especially whole grains, and fatty fish, as well as adherence to the Mediterranean dietary pattern, was associated with a lower risk for CRC. Future studies are needed to better understand the influence of the dietary habits on CRC prevention in this population that can provide leads for the design and tailoring of future interventions, and guide counselling strategies for promoting a healthy lifestyle. Citation: Alegria-Lertxundi I, Aguirre C, Bujanda L, Fernández FJ, Polo F, Ordovás JM, Etxezarraga MC, Zabalza I, Larzabal M, Portillo I, de Pancorbo MM, Garcia-Etxebarria K, Rocandio AM, Arroyo-Izaga M. Food groups, diet quality and colorectal cancer risk in the Basque Country. World J Gastroenterol 2020; 26(28): 4108-4125 Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4110 July 28, 2020 Volume 26 Issue 28 2020 First decision: March 21, 2020 Revised: April 3, 2020 Accepted: July 16, 2020 Article in press: July 16, 2020 Published online: July 28, 2020 P-Reviewer: Bordonaro M, Khajehei M S-Editor: Zhang L L-Editor: A E-Editor: Zhang YL URL: https://www.wjgnet.com/1007-9327/full/v26/i28/4108.htm DOI: https://dx.doi.org/10.3748/wjg.v26.i28.4108 INTRODUCTION Colorectal cancer (CRC) is a major public health challenge worldwide. CRC is the third-most commonly diagnosed malignancy and the fourth leading cause of cancer deaths in the world, accounting for approximately 1.8 million new cases and almost 900000 deaths in 2018[1]. In Europe, CRC is the leading malignancy in terms of incidence and the second in mortality in both sexes[2]. CRC is linked to western lifestyles, in particular, to diet, physical inactivity, smoking, alcohol consumption, and body weight[3,4]. Epidemiological evidence suggests that dietary factors may both protect against and promote the development of CRC. A comprehensive review[5] shows robust evidence about the protective role of dietary fiber. Other foods, such as milk or garlic, also may be protective. Conversely, red meat and processed meat intake and alcoholic drinks increase CRC risk. This food group approach has the advantage of reducing some of the problems inherent to analyses of nutrient intake (e.g., inaccuracy and incompleteness of food-composition tables). Furthermore, it offers an advantage from a preventive perspective since food group results are easier to transform into dietary recommendations than those of nutrients[6]. In this regard, foods are not consumed in isolation but as part of a dietary pattern; therefore, the actual effect of diet on disease risk may be observed only when all components are considered jointly[6]. For this purpose, several diet quality indexes have been developed using point systems to measure whole diet quality based on the alignment of food choices with dietary recommendations. Some of these indices have been used to begin assessing the relationships between overall diet quality and CRC risk, and the results show that high scores in these indices are associated with a lower CRC risk[7-10]. However, the results vary considerably according to the index used and other factors such as sex and age. Therefore, there is a need to further examine these relationships in diverse population studies. The current case-control study was undertaken in the North of Spain to elucidate the relationships between food group consumption, diet quality and CRC risk, and identify possible differences in consumption depending on tumor location, in an adult population that participated in a CRC screening programme (CRCSP) in the Basque Country. To our knowledge, this is the first study in the Basque country population, in which both CRC incidence and mortality have increased in recent years[11]. There are few studies in this regard in Spain[12,13]. And both in these Spanish studies and in others carried out in other Mediterranean countries controls were apparently healthy subjects without clinical symptoms or signs of any type of cancer[14]. MATERIALS AND METHODS Study subjects This is an observational, matched case-control study in a population group residing in the Basque Country (North of Spain). Participants in this study were recruited from among patients attending any of the three hospitals of the Osakidetza/Basque Health Service (Basurto, Galdakao and Donostia) members of the Basque Country CRCSP. To be eligible for this CRCSP, the patients had to be aged between 50 and 69, asymptomatic for colorectal symptoms and registered with the Osakidetza/Basque Health Service[11]. These inclusion criteria were applied to both case and control group, that is, controls fulfilled the same eligibility criteria defined for the cases, with the exception of the disease (outcome). Recruitment and data collection for the present study were conducted between 2014 and 2016. All the patients who were newly diagnosed with CRC (n = 601) were invited to participate in this study. Of those, 283 refused to participate in the study, and 10 were excluded due to missing information. Ultimately, 308 subjects (66.2% men) consented to participate in the survey and completed all the questionnaires. In addition, for each case, three age- (± 9.0 years) and sex-matched control patients were randomly sought from the list of CRC-free subjects (n = 1836) who participated in the CRCSP during the same period as the cases. The matched controls were patients with positive results Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4111 July 28, 2020 Volume 26 Issue 28 (abnormal) for immunochemical fecal occult blood test and negative colonoscopy results (normal). The participation rate of the controls was 37.6%, and 17 subjects were excluded due to missing information. Finally, the matched case-to-control ratio was 1:1, and the final data set included 308 cases who were diagnosed with CRC and 308 ageand sex-matched controls. Further details on recruitment and data collection have been described elsewhere[15]. The main advantage of the present study compared to other above-mentioned researches[12-14] is that we confirmed that controls were free of the disease through colonoscopy. Colonoscopy was used as diagnostic criteria to identify the cases in order to avoid false positives and negatives. The pathological staging was based on the 7th edition of the AJCC cancer staging manual[16] as follows: I (57.1%), IIA (13.6%), IIB (1.0%), IIC (0.3%), IIIA (7.5%), IIIB (14.6%), IIIC (1.9%), IVA (2.9%), and IVB (1.0%). The location of the cancer was distal in 76% and proximal (to the splenic flexure of the colon) in 24.0% of the samples. Concerning the tumor grade classification, we adopted a two-grade classification that was divided into low grade (well or moderately differentiated) (80.5%) and high grade (poorly differentiated, anaplastic, or undifferentiated) (4.5%); the percentage of missing data for this classification was 14.9%. Some of the cases had undergone surgical resection (73.7%) and/or adjuvant treatments, chemotherapy (34.1%), and chemotherapy and radiation (6.8%). The percentages of subjects according to the type of surgical procedure were as follows: 26.3% sigmoidectomy, 17.5% right hemicolectomy resection, 18.8% low anterior resection, 6.5% left hemicolectomy resection, 2.3% transverse colectomy, 1.0% abdominoperineal resection, 1.0% total colectomy, and 0.3% transanal endoscopic operation. The cases were invited to take part in this survey at least one month after finishing their last treatment (surgery, chemotherapy or radiotherapy) (median, 1.3 years; range, 0.1 to 4.2 years). All the clinical data were obtained from the Basque Country's population-based CRCSP database, which links patient medical records and clinical databases and reviewed by expert staff. This review allowed the monitorization of all cases from the submission of the sample through the analysis, colonoscopy, pathology and follow-up. This study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving patients were approved by the Clinical Research Ethics Committee of the Basque Country (reference numbers PI2011006 and PI2014042). Written informed consent was obtained from all the study participants. Consenting participants self-completed and returned a detailed food frequency questionnaire (FFQ) and one general questionnaire. The questions referred to the behaviors before participating in the CRCSP. Assistance from the study staff was available to help the patients to understand the items on the questionnaires. The quality management applied in the present study has been described in a previous article[15]. Dietary assessment Diets were assessed using a short FFQ that was a modified version of the Rodríguez et al[17] (2008) questionnaire. This adaptation was validated with multiple 24-h recalls in the Basque general population[18] and in CRC diagnosed patients in a pilot of the present study[19]. It consists of 67 items and requires the subjects to recall the number of times each food item was consumed either per week or per month. This FFQ included specific questions about the frequency of intake of alcoholic beverages. Moreover, the respondents could also record the consumption of other foods that were not included on the food list. Consumption frequencies were standardized to “per day” and multiplied by standard serving sizes (grams)[20]. For items that included several foods, each food’s contribution was estimated with weighting coefficients that were obtained from the usual consumption data[21]. Food items were then regrouped according to nutritional characteristics[22] and considering the potential contribution of food to the pathogenesis of CRC[23,24]. Details on the items included in each food group are shown in Table 1. All food items that were consumed were entered into DIAL 2.12 (2011 ALCE INGENIERIA)[25], a type of dietary assessment software, to estimate energy intake ( kilocalories/day, kcal/d). Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for Spanish Diet (HEISD)[26] and the MedDietScore (MDS)[27], as previously described[19]. The theoretical range of the HEISD is 0-100 and of the MDS 055, higher values of these scores indicate greater adherence to the dietary recommendations for the Spanish population and the Mediterranean diet pattern, respectively. HEISD was divided into the following categories: Poor diet (< 50 points), needs improvement (50-80 points) and proper diet (> 80 points)[26]; and the MDS into Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4112 July 28, 2020 Volume 26 Issue 28 Table 1 Food group definitions Food group Food items Red and processed meat Red meat Beef, pork and lamb, minced meat, hamburgers, meatballs Processed meat Ham, sausage, salami, mortadella, black pudding or blood sausage Egg Egg Fish White fish (hake, grouper, sole, cod) and fatty fish (sardine, tuna, salmon, mackerel) Milk/dairy products Non-cheese products Whole milk, semi-skimmed milk, skimmed milk, whole yogurt, skimmed yogurt and dairy desserts Cheese Burgos cheese, curd, cottage and cheeses low in calories, mature, semi-mature and creamy cheese Fiber-containing foods Fruits Orange, tangerine, apple, pear, banana, peach, raisins, prunes, dried figs... natural fruit juices Vegetables Salads, green beans, chard, spinach... garnish vegetables (eggplant, mushrooms, peppers...), garlic, onion Whole grains Whole grain pasta, brown rice, whole grain cookies, whole breakfast cereals (Muesli, All-Bran) Nuts Walnuts, almonds, hazelnuts, peanuts Fat Vegetable oils (olive, sunflower, corn, soy), butter, margarine, mayonnaise Sweet and added sugar Chocolate, breakfast cereals, cookies, muffins, donuts, honey, sugar, commercial fruit juice, soft-drinks, cakes, pies Alcoholic beverages Beer, wine, hard cider, vermouth, whiskey, rum, gin, brandy, cocktails the following ones: Low adherence to MD (0-34 points) and high adherence (> 35 points). The cut-off point of MDS was established taking into account that scores below 34 points were associated with a higher risk of coronary heart disease, being the relative odds ≥ 1.42[27]. General questionnaire A general questionnaire was used to gather information on weight status (selfreported weight and height) and environmental factors [demographic factors: Age and sex; and lifestyle information: Physical exercise (PE) and smoking consumption]. These questions were taken from the Spanish Health Questionnaire[28]. Body mass index (BMI) estimated from self-reported height and weight was classified according to the World Health Organization criteria for those under 65 years of age[29] and according to the criteria proposed by Silva Silva Rodrigues et al[30] for those 65 years and older. Additionally, socioeconomic and health status data were assessed with two indices that were obtained from the clinical databases developed by the Health Department of the Basque Government, namely the socioeconomic deprivation index (DI) and predictive risk modelling (PRM), respectively. The first one was estimated using the MEDEA project criteria[31], as has been described elsewhere[12] and was divided into quintiles (Q), with the first being the least disadvantaged and the fifth being the most disadvantaged. The DI was successfully assigned to 80.2% of participants, while the quality of the registered information did not permit the linking of the remaining 19.8%. The PRM is an index that is based on Adjusted Clinical Groups[32], Diagnostic Cost Groups/Hierarchical Condition Categories[33] and Clinical Risk Groups[34]. This index combines information about diagnoses, prescriptions, previous costs and the use of specific procedures. It is capable of predicting the use of health resources[35], and it was stratified into four levels (L); the first included participants with a risk of high health resource consumption and the fourth included those with low health resource consumption. The PRM was successfully assigned to 95.1% of participants, while the quality of the registered information did not permit the linking of the remaining 4.9%. Statistical analysis Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, United States) and STATA 13.0 (StataCorp LP, TX, United States). Categorical variables are shown as a percentage, and continuous variables are shown as the means and standard deviations (SD). Normality was Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4119 July 28, 2020 Volume 26 Issue 28 P0.789 < 0.001 - Whole grains T1144/128 1.00 1.00 1.00 T283/77 0.92 (0.62-1.38) 0.86 (0.52-1.42) 0.98 (0.58-1.65) T381/103 0.68 (0.46-1.01) 0.62 (0.37-1.06) 0.62 (0.39-0.98) P0.135 < 0.001 1Food groups consumption was categorized into tertiles according to the distribution in controls, and by sexes for food groups with significant differences according to sex; Tertiles of food groups: Red meat, T1 < 33.5, T2 33.5-54.9, T3 > 54.9; Processed meat, T1 < 11.6, T2 11.6-22.8, T3 > 22.8; non-cheese dairy, T1 < 225.0, T2 225.0-325.0, T3 > 325.0; Cheese, T1 < 7.5, T2 7.5-20.0, T3 > 20.0; Vegetables, T1 < 152.9, T2 152.9-237.2, T3 > 237.2;Tertiles of food groups for men: Fruits, T1 < 207.5, T2 207.5-392.9, T3 > 392.9; Whole grains, T1 < 1.0, T2 1.0-17.5, T3 > 17.5; Tertiles of food groups for women: Fruits T1 < 242.9, T2 242.9425.0,: Whole grains, T1 < 2.0, T2 2.0-30.0, T3 > 30.0. 2Model I, analyses were performed using crude conditional logistic regression, without taking into account confounding factors. 3Model II, analyses were performed using conditional logistic regression analysis adjusted for age (50-59 years old, 60-69 years old), sex, body mass index (underweight/normal weight, overweight/obesity), energy intake (kcal/d), physical exercise level (< 15 min/d of cycling/sports, ≥ 15 min/d), smoking status and intensity of smoking (never; past: quit smoking ≥ 11 years ago, quit < 11 years ago; Smoker: ≤ 15 cigarettes/d, > 15 cigarettes/d), Deprivation Index (quintile 1-3, quintile 4-5) and Predictive Risk Modelling (level 1-2, level 3-4), including food groups separately; Participants with missing data for the confounding variables were included as a separate category for these variables. 4Model III, model II including all the mean food groups. CI: Confidence interval; OR: Odd ratio; T: Tertile. interfering absorption of those, and lowering intestinal acidity[51]. In addition, fermentation of fiber produced butyrate. This short-chain fatty acid showed antiinflammatory, anti-proliferation and antineoplastic properties in colonocyte cells metabolism through microbiota homeostasis and genetic/epigenetic regulation[52]. Furthermore, our findings suggest that high consumption of whole grains (higher than 17.5 g/d in men and 30.0 g/d in women) may decrease the risk of CRC, after controlling confounding factors. There is convincing evidence that whole grains help to reduce CRC risk[5,53]. The observed reduction in CRC risk associated with high consumption of whole grains may partly be attributed to dietary fiber, resistant starch, and oligosaccharides that can influence the gut environment. Insoluble fiber increases the bulk of luminal contents, diluting potential carcinogens and promoters in the colon and decreasing transit time, and, consequently, reduces the exposure of the colonic epithelium to harmful compounds[54,55]. Additionally, other components such as vitamins (especially B-vitamins), minerals (e.g., magnesium and zinc), phenolic compounds, antinutrients (e.g., tannins), and phytoestrogens may also contribute to this protection[54]. On the other hand, the consumption of fatty fish (higher than 42.8 g/d) was associated with a decreased risk in CRC by about 50% (OR approximately 0.5) compared to lower consumption, after adjusting models for covariates. It should be noted that the Basque Country population has a higher consumption of total fish and fatty fish compared to other Spanish autonomous communities[55,56]. Recent cohort studies have observed that fatty fish was inversely associated with CRC incidence[57,58] and they have related this association with exposure to long-chain n-3 polyunsaturated fatty acids[57]. Evidence from animal and in vitro studies indicates that n-3 fatty acids present in fatty fish may inhibit carcinogenesis[59]. High intake of n-3 fatty acids suppresses the production of arachidonic acid-derived eicosanoids such as prostaglandin E2 and leukotriene B431. N-3 fatty acids could also suppress the expression of inducible nitric oxide synthase and nuclear transcription factor κ B (NF-κ B)[60]. In relation to the diet quality, our findings on the MDS and CRC risk are supported by those of other researchers[13,61-63], who found significant associations between lower risk of CRC and adherence to Mediterranean dietary pattern. However the HEISD was not associated with CRC risk, discrepancies in results obtained with the two dietary quality indices analysed are probably due to differences in their constructs and scoring criteria. The overall MDS was inversely associated with CRC risk, being higher the total score in cases with the proximal location of cancer than for those with the distal location. These last results contrast with previous findings, which showed that the protective effects of adherence to the MD were mainly for distal colon and rectal cancer and not for proximal colon cancer[64]. In the total sample, investigation of the separate score components showed that whole grain score was lower for cases than for controls. This result is consistent with that obtained for the association between whole grains consumption and CRC risk. Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4120 July 28, 2020 Volume 26 Issue 28 Table 6 Diet quality indices in the sample studied Cases (n = 308) Controls (n = 308) mean SD mean SD P value HEISD components1 Meats 3.1 1.7 3.1 1.7 0.811 Processed meats 2.8 2.0 3.1 2.2 0.162 Legumes 8.6 2.1 8.5 2.3 0.716 Milk/Dairy 9.8 1.2 9.8 1.1 0.797 Fruits 9.1 1.8 9.1 1.9 0.464 Vegetables 8.9 1.7 8.9 1.6 0.816 Grains 9.9 0.9 9.9 1.9 0.862 Sweets 1.6 3.1 1.6 3.0 0.847 Soft-drink 8.8 2.5 8.7 2.6 0.583 Variety 8.0 1.7 8.0 1.7 0.646 Total HEISD 70.7 7.2 70.8 7.9 0.906 MDS components2 Red meats and processed meats 0.7 1.0 0.8 1.2 0.134 Poultry 2.9 1.2 2.9 1.2 0.335 Fish 3.8 1.1 3.8 1.2 0.771 Legumes 2.4 1.2 2.3 1.1 0.482 Full fat dairy 2.0 1.8 2.0 1.9 0.618 Vegetables 4.9 0.6 4.9 0.5 0.599 Fruits 4.6 1.0 4.6 1.0 0.726 Potatoes 2.2 1.5 2.4 1.5 0.054 Whole grains 2.0 2.2 2.3 2.3 0.044 Alcoholic beverages 4.9 0.4 4.9 0.4 0.729 Olive oil 4.9 0.6 4.8 0.8 0.446 Total MDS 35.3 4.5 36.0 4.3 0.027 1Each component can contribute 10 points to the total score and the theoretical range is 0–100. 2Each component can contribute five points to the total score and the theoretical range is 0–55. HEISD: Healthy Eating Index for Spanish Diet; MDS: Med Diet Score; SD: Standard deviation. Our study has several limitations. First, recall bias inherent in a case-control study design cannot be ruled out. The primary concern of this study is the low participation rate, which may have limited the representativeness of study samples. The decision to participate or not may be influenced by several factors, including social, educational and health conditions, which may again correlate with outcome risk factors. Second, self-reported data could be subject to measurement errors and the problem of food omissions due to memory failure and underreporting of unhealthy habits among disease subjects. However, previous validation studies indicate that the self-reported dietary information is reported with sufficient accuracy for use in epidemiology analyses[65]; and it should be noted that dietary changes are usually modest after participating in the CRCSP due to a lack of information and personalized advice[66,67]. Another limitation of this type of study could be the selection of controls (selection bias). To avoid this type of bias, we obtained controls from the same CRCSP and in the same period as cases, thus, it was confirmed that they did not suffer from CRC by colonoscopy. Despite these limitations, the results allow us to conclude that high consumption of high-fat cheeses is associated with CRC risk, whereas, a high intake of fiber-containing Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4121 July 28, 2020 Volume 26 Issue 28 foods, especially whole grains, and fatty fish, and adherence to the Mediterranean dietary pattern was associated with a lower risk for CRC. Future studies are needed to better understand the influence of the dietary habits on CRC prevention in this population that can provide leads for the design and tailoring of future interventions, and guide counselling strategies for promoting a healthy lifestyle. ARTICLE HIGHLIGHTS Research background Epidemiological evidence suggests that some foods may both protect against and promote the development of colorectal cancer (CRC). However, foods are not consumed in isolation but as part of a dietary pattern; therefore, the actual effect of diet on disease risk may be observed only when all components are considered jointly. For this purpose, several diet quality indexes have been developed using point systems to measure whole diet quality based on the alignment of food choices with dietary recommendations. Research motivation Some diet quality indexes have been used to begin assessing the relationships between overall diet quality and CRC risk, and the results show that high scores in these indices are associated with a lower CRC risk. However, the results vary considerably according to the index used and other factors such as sex and age. Therefore, there is a need to further examine these relationships in diverse population studies. Research objectives To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). Research methods This observational study included 308 patients diagnosed with CRC and 308 ageand sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Dietary intake was assessed using a short food frequency questionnaire that was adapted and validated for this population. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, United States) and STATA 13.0 (StataCorp LP, TX, United States). Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. Research results The adjusted models for potential confounding factors showed a direct association between milk/dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR = 0.40, 95%CI: 0.20-0.80). Research conclusions Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern. Research perspectives Future studies are needed to better understand the influence of the dietary habits on CRC prevention in this population that can provide leads for the design and tailoring of future interventions, and guide counselling strategies for promoting a healthy lifestyle. Alegria-Lertxundi I et al. Diet and colorectal cancer risk WJG https://www.wjgnet.com 4122 July 28, 2020 Volume 26 Issue 28 REFERENCES Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424 [PMID: 30207593 DOI: 10.3322/caac.21492] 1 Altobelli E, Lattanzi A, Paduano R, Varassi G, di Orio F. Colorectal cancer prevention in Europe: burden of disease and status of screening programs. Prev Med 2014; 62: 132-141 [PMID: 24530610 DOI: 10.1016/j.ypmed.2014.02.010] 2 Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. 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