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      Gene–Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case–Control Study in the Basque Country

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          Abstract

          Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze differences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p < 0.05), a lower intake of vitamin B 2 (0.86 ± 0.23 vs. 0.92 ± 0.23 mg/1000 kcal, p < 0.01) and calcium:phosphorus ratio (0.62 ± 0.12 vs. 0.65 ± 0.13, p < 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p < 0.001) or cholesterol (35.4% vs. 25.0%, p < 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.

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          Colorectal Cancer and Nutrition

          Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer.
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            Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence.

            The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels. Epidemiological studies show that the inclusion of wholegrain, fibre, fruits, and vegetables within diets are associated with reduced cancer risk, with diet during early life (age <8 years) having the strongest apparent association with cancer incidence. However, randomised controlled trials of diet-related factors have not yet shown any conclusive associations between diet and cancer incidence. Obesity is a key contributory factor associated with cancer risk and mortality, including in dose-response associations in endometrial and post-menopausal breast cancer, and in degree and duration of fatty liver disease-related hepatocellular carcinoma. Obesity produces an inflammatory state, characterised by macrophages clustered around enlarged hypertrophied, dead, and dying adipocytes, forming crown-like structures. Increased concentrations of aromatase and interleukin 6 in inflamed breast tissue and an increased number of macrophages, compared with healthy tissue, are also observed in women with normal body mass index, suggesting a metabolic obesity state. Emerging randomised controlled trials of physical activity and dietary factors and mechanistic studies of immunity, inflammation, extracellular matrix mechanics, epigenetic or transcriptional regulation, protein translation, circadian disruption, and interactions of the multibiome with lifestyle factors will be crucial to advance this field.
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              Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer.

              Sporadic colorectal cancer (CRC) is a somatic genetic disease in which pathogenesis is influenced by the local colonic environment and the patient's genetic background. Consolidating the knowledge of genetic and epigenetic events that occur with initiation, progression, and metastasis of sporadic CRC has identified some biomarkers that might be utilized to predict behavior and prognosis beyond staging, and inform treatment approaches. Modern next-generation sequencing of sporadic CRCs has confirmed prior identified genetic alterations and has classified new alterations. Each patient's CRC is genetically unique, propelled by 2-8 driver gene alterations that have accumulated within the CRC since initiation. Commonly observed alterations across sporadic CRCs have allowed classification into a (1) hypermutated group that includes defective DNA mismatch repair with microsatellite instability and POLE mutations in ∼15%, containing multiple frameshifted genes and BRAF(V600E); (2) nonhypermutated group with multiple somatic copy number alterations and aneuploidy in ∼85%, containing oncogenic activation of KRAS and PIK3CA and mutation and loss of heterozygosity of tumor suppressor genes, such as APC and TP53; (3) CpG island methylator phenotype CRCs in ∼20% that overlap greatly with microsatellite instability CRCs and some nonhypermutated CRCs; and (4) elevated microsatellite alterations at selected tetranucleotide repeats in ∼60% that associates with metastatic behavior in both hypermutated and nonhypermutated groups. Components from these classifications are now used as diagnostic, prognostic, and treatment biomarkers. Additional common biomarkers may come from genome-wide association studies and microRNAs among other sources, as well as from the unique alteration profile of an individual CRC to apply a precision medicine approach to care.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                07 August 2020
                August 2020
                : 12
                : 8
                : 2362
                Affiliations
                [1 ]Department of Pharmacy and Food Sciences. Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain; lertxundi83@ 123456gmail.com (I.A.-L.); anamaria.rocandio@ 123456ehu.eus (A.M.R.)
                [2 ]Pharmacovigilance Unit, Galdakao-Usansolo University Hospital, Osakidetza, 48960 Galdakao, Spain; carmelo.aguirregomez@ 123456osakidetza.eus
                [3 ]Department of Gastroenterology, Donostia University Hospital/Biodonostia Health Research Institute, University of the Basque Country UPV/EHU, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 20014 San Sebastian, Spain; luis.bujandafernandezdepierola@ 123456osakidetza.eus
                [4 ]Department of Gastroenterology, Galdakao-Usansolo University Hospital, Osakidetza, 48960 Galdakao, Spain; franciscojavier.fernandezfernandez@ 123456osakidetza.eus
                [5 ]Department of Gastroenterology, Basurto University Hospital, Osakidetza, 48013 Bilbao, Spain; franciscopolo2001@ 123456gmail.com
                [6 ]Nutrition and Genomics Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA; Jose.Ordovas@ 123456tufts.edu
                [7 ]Institute IMDEA Food, Institutos Madrileños de Estudios Avanzados (IMDEA), 28049 Madrid, Spain
                [8 ]Department of Pathology, Basurto University Hospital, Osakidetza, 48013 Bilbao, Spain; mariacarmen.etxezarragazuluaga@ 123456osakidetza.eus
                [9 ]Department of Physician and Surgeon Specialities, University of the Basque Country UPV/EHU, 48940 Leioa, Spain
                [10 ]Department of Pathology, Galdakao-Usansolo University Hospital, Osakidetza, 48960 Galdakao, Spain; ignacio.zabalzaestevez@ 123456osakidetza.eus
                [11 ]Department of Pathology, Donostia Hospital/Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 20014 San Sebastian, Spain; josemiguel.larzabalaramberri@ 123456osakidetza.net
                [12 ]Central Coordinating Center of the Bowel Cancer Screening Program, Healthcare subdirectorate, Osakidetza, 48011 Bilbao, Spain; mariaisabel.portillovillares@ 123456osakidetza.eus
                [13 ]BIOMICs Research Group, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain; marian.mdepancorbo@ 123456ehu.eus (M.M.d.P.); leire.palencia@ 123456ehu.eus (L.P.-M.)
                [14 ]Biodonostia Health Research Institute, Gastrointestional genetics group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 20014 San Sebastian, Spain; koldo.garcia@ 123456biodonostia.org
                Author notes
                [* ]Correspondence: marta.arroyo@ 123456ehu.eus
                Author information
                https://orcid.org/0000-0002-6702-9209
                https://orcid.org/0000-0002-7581-5680
                https://orcid.org/0000-0002-3871-3423
                https://orcid.org/0000-0002-4351-3450
                https://orcid.org/0000-0002-6107-9416
                https://orcid.org/0000-0001-5592-4241
                Article
                nutrients-12-02362
                10.3390/nu12082362
                7468855
                32784647
                a01b5579-e409-46e1-840b-1a5061495eea
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 July 2020
                : 31 July 2020
                Categories
                Article

                Nutrition & Dietetics
                colorectal cancer,diet,genetic factors,gene–diet interactions,risk-factors,case–control study

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