Top

Open Access 23-04-2024 | Colorectal Cancer | Original Contribution

Interactions between folate metabolism-related nutrients and polymorphisms on colorectal cancer risk: a case-control study in the Basque country

Authors: Sara Corchero-Palacios, Iker Alegria-Lertxundi, Marian M. de Pancorbo, Marta Arroyo-Izaga

Published in: European Journal of Nutrition

Abstract

Folate-mediated one-carbon metabolism (FOCM) plays an important role in colorectal carcinogenesis. Previous studies have assessed the role of folate-mediated one-carbon metabolism (FOCM)-related gene-diet interaction in the aetiology of colorectal cancer (CRC), however, the results remained inconclusive. Thus, this study aimed to investigate dietary factors and genetic variants related to FOCM, as well as potential nutrient-gene and nutrient-lifestyle interactions, on CRC risk. This observational study included 229 patients diagnosed with CRC and 229 age- and sex-matched subjects as controls from a population-based bowel cancer screening program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) for CRC risk. A Bonferroni-corrected threshold of α = 0.005 was considered significant, and P values less than 0.05 were considered to be suggestive of an association. After Bonferroni correction, a high dietary intake of betaine was associated with a decreased risk of CRC in the adjusted model (OR, 95% CI: 0.21, 0.10–0.40, P < 0.001). Two SNPs, rs1476413 and rs17824591, exhibited significant gene-diet interactions with total choline ad vitamin B₁₂ intakes, respectively, in adjusted models (total choline, tertile 3 vs. 1, OR, 95% CI: 0.25, 0.11–0.66, P_interaction = 0.012; vitamin B₁₂, tertile 2 vs. tertile 1, OR, 95% CI: 2.48, 1.04-5.00, P_interaction = 0.003). These findings suggest that betaine intake and interactions between some dietary factors and variants in MTHFR and MTHFD1 genes have an influence on CRC risk in the population studied. If these results are confirmed, specific nutritional intervention strategies could be designed.

Available only for authorised users

Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, Vignat J, Ferlay J, Murphy N, Bray F (2023) Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut 72(2):338–344. https://doi.org/10.1136/gutjnl-2022-327736CrossRefPubMed

Cancer Observatory of the Spanish Association against Cancer (2022) Accessed December 28, 2023. https://observatorio.contraelcancer.es/

World Health Organization. Cancer Today. Global Cancer Observatory [GCO] (2020) Accessed December 28, 2023. http://gco.iarc.fr/today

Keum N, Giovannucci E (2019) Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol 16(12):713–732. https://doi.org/10.1038/s41575-019-0189-8CrossRefPubMed

Choi SW, Mason JB (2002) Folate status: effects on pathways of colorectal carcinogenesis. J Nutr 132(8 Suppl). https://doi.org/10.1093/jn/132.8.2413s. :2413S-2418S

Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, Negri E, Straif K, Romieu I, La Vecchia C, Boffetta P, Jenab M (2011) Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol 22(9):1958–1972. https://doi.org/10.1093/annonc/mdq653CrossRefPubMed

Liu AY, Scherer D, Poole E, Potter JD, Curtin K, Makar K, Slattery ML, Caan BJ, Ulrich CM (2013) Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon cancer risk. Mol Nutr Food Res 57(4):721–734. https://doi.org/10.1002/mnfr.201200180CrossRefPubMed

Alegria-Lertxundi I, Aguirre C, Bujanda L, Fernández FJ, Polo F, Ordovás JM, Etxezarraga MC, Zabalza I, Larzabal M, Portillo I, M de Pancorbo M, Palencia-Madrid L, Garcia-Etxebarria K, Rocandio AM, Arroyo-Izaga M (2020) Gene-diet interactions in colorectal cancer: survey design, instruments, participants and descriptive data of a case-control study in the Basque Country. Nutrients 12(8):2362. https://doi.org/10.3390/nu12082362CrossRefPubMedPubMedCentral

Rodríguez IT, Ballart JF, Pastor GC, Jordà EB, Val VA (2008) Validación De Un Cuestionario De frecuencia de consumo alimentario corto: reproducibilidad y validez [Validation of a short questionnaire on frequency of dietary intake: reproducibility and validity]. Nutr Hosp 23(3):242–252 PMID: 18560701PubMed

10.

Telleria-Aramburu N, Alegria-Lertxundi I, Arroyo-Izaga M (2021) Adaptation, validation and reproducibility of a short FFQ to assess food group intake in the population resident in the basque country (Spain). Public Health Nutr 24(3):436–448. https://doi.org/10.1017/s1368980020001822CrossRefPubMed

11.

Alegria-Lertxundi I, Alvarez M, Rocandio AM, de Pancorbo MM, Arroyo-Izaga M (2016) Nutritional adequacy and diet quality in colorectal cancer patients postsurgery: a pilot study. Nutr Cancer 68(4):577–588. https://doi.org/10.1080/01635581.2016.1158299CrossRefPubMed

12.

Carbajal A, Sánchez-Muniz FJ, Secretariat of Publications and Audiovisual Media (2003) Guía de prácticas en Nutrición y Dietética [Guide to Practices in Nutrition and Dietetics]. University of León, ; :1–3. Accessed December 10, 2020. https://www.ucm.es/data/cont/docs/458-2019-01-04-Guia-Practicas-2019-web.pdf

13.

Department of Agriculture, Fisheries and Food, Basque Government. Estudio cuantitativo del consumo de alimentos en la CAPV [Quantitative study of food consumption in the autonomous community of the Basque Country]. Basque Government: Central Publication Service (2008) Accessed December 9, 2020. https://www.euskadi.eus/contenidos/informacion/coleccion_elika/es_dapa/adjuntos/Guia_Elika_8.pdf

14.

U.S. Department of Agriculture, Agricultural Research Service. USDA’s FoodData Central (2017) Accessed August 9, 2018. https://fdc.nal.usda.gov/

15.

Zeisel SH, Mar MH, Howe JC, Holden JM (2003) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133(5):1302–1307. https://doi.org/10.1093/jn/133.5.1302CrossRefPubMed

16.

Iles-Shih L, Collins JF, Holub JL, Lieberman DA (2010) Prevalence of significant neoplasia in FOBT-positive patients on warfarin compared with those not on warfarin. Am J Gastroenterol 105(9):2030–2035. https://doi.org/10.1038/ajg.2010.264CrossRefPubMed

17.

Ministry of Health, Social Services and Equality, Government of Spain / National Statistics Institute. Encuesta Nacional de Salud. España 2011/12 [National Health Survey, Spain 2011/12]. Accessed December 20 (2019) http://www.msssi.gob.es/estadEstudios/estadisticas/sisInfSanSNS/nivelSalud.htm

18.

World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO consultation, 2000. Accessed December 5 (2019) https://apps.who.int/iris/handle/10665/42330

19.

Silva Rodrigues RA, Martinez Espinosa M, Duarte Melo C, Rodrigues Perracini M, Rezende Fett WC, Fett CA (2014) New values anthropometry for classification of nutritional status in the elderly. J Nutr Health Aging 18(7):655–661. https://doi.org/10.1007/s12603-014-0451-2CrossRefPubMed

20.

Serra-Majem L, Aranceta J, SENC Working Group on Nutritional Objectives for the Spanish Population (2001) Spanish Society of Community Nutrition. Nutritional objectives for the Spanish population. Consensus from the Spanish Society of Community Nutrition. Public Health Nutr 4(6A):1409–1413. https://doi.org/10.1079/phn2001229CrossRefPubMed

21.

Ministry of Health and Consumption, Government of Spain. Informes de la Comisión Clínica 2017: Alcohol [Clinical Commission Reports: Alcohol]. Accessed December 10 (2019) http://www.pnsd.msc.es/Categoria2/publica/pdf/InformeAlcohol.pdf

22.

Alegria-Lertxundi I, Aguirre C, Bujanda L, Fernández FJ, Polo F, Ordovás JM, Etxezarraga MC, Zabalza I, Larzabal M, Portillo I, de Pancorbo MM, Palencia-Madrid L, Rocandio AM, Arroyo-Izaga M (2019) Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: case-control study in a basque population. PLoS ONE 14(12):e0225779. https://doi.org/10.1371/journal.pone.0225779CrossRefPubMedPubMedCentral

23.

Orueta JF, Nuño-Solinis R, Mateos M, Vergara I, Grandes G, Esnaola S (2013) Predictive risk modelling in the Spanish population: a cross-sectional study. BMC Health Serv Res 13:269. https://doi.org/10.1186/1472-6963-13-269CrossRefPubMedPubMedCentral

24.

School of Public Health, Johns Hopkins University. The Johns Hopkins University ACG Case-Mix System. Accessed August 10 (2012) http://www.acg.jhsph.org/index.php?option=com_content&view=article&id=46&Itemid=61

25.

Verisk Analytics, Inc. DxCG® Introduces Disease Management Calculator. Accessed August 10 (2012) https://www.verisk.com/archived/dxcg-introduces-disease-management-calculator/

26.

de Vogel S, Wouters KA, Gottschalk RW, van Schooten FJ, de Goeij AF, de Bruïne AP, Goldbohm RA, van den Brandt PA, van Engeland M, Weijenberg MP (2011) Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet-gene interactions and promoter CpG island hypermethylation in colorectal cancer. Cancer Causes Control 22(1):1–12. https://doi.org/10.1007/s10552-010-9659-6CrossRefPubMed

27.

Li H, Liu JW, Sun LP, Yuan Y (2017) A Meta-analysis of the association between DNMT1 polymorphisms and cancer risk. Biomed Res Int 2017:3971259. https://doi.org/10.1155/2017/3971259CrossRefPubMedPubMedCentral

28.

Ashmore JH, Lesko SM, Muscat JE, Gallagher CJ, Berg AS, Miller PE, Hartman TJ, Lazarus P (2013) Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population-based case-control study. Genes Chromosomes Cancer 52(10):945–953. https://doi.org/10.1002/gcc.22089CrossRefPubMed

29.

Pardini B, Kumar R, Naccarati A, Prasad RB, Forsti A, Polakova V, Vodickova L, Novotny J, Hemminki K, Vodicka P (2011) MTHFR and MTRR genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from the Czech Republic. Mutat Res 721(1):74–80. https://doi.org/10.1016/j.mrgentox.2010.12.008CrossRefPubMed

30.

Service of Epidemiology (2004) Dirección Xeral de Saúde Pública, Consellería de Sanidade, Xunta de Galicia, Spain; Unit of Health Analysis and Information Systems, Pan-American Health Organization (PAHO), Washington, DC. Epidat 3.0 program. Santiago de Compostela, A Coruña, Spain

31.

Torres Stone RA, Waring ME, Cutrona SL, Kiefe CI, Allison J, Doubeni CA (2017) The association of dietary quality with colorectal cancer among normal weight, overweight and obese men and women: a prospective longitudinal study in the USA. BMJ Open 7(6):e015619. https://doi.org/10.1136/bmjopen-2016-015619CrossRefPubMedPubMedCentral

32.

Doubeni CA, Laiyemo AO, Major JM, Schootman M, Lian M, Park Y, Graubard BI, Hollenbeck AR, Sinha R (2012) Socioeconomic status and the risk of colorectal cancer: an analysis of more than a half million adults in the National Institutes of Health-AARP Diet and Health Study. Cancer 118(14):3636–3644. https://doi.org/10.1002/cncr.26677CrossRefPubMed

33.

Romaguera D, Vergnaud AC, Peeters PH, van Gils CH, Chan DS, Ferrari P, Romieu I, Jenab M, Slimani N, Clavel-Chapelon F, Fagherazzi G, Perquier F, Kaaks R, Teucher B, Boeing H, von Rüsten A, Tjønneland A, Olsen A, Dahm CC, Overvad K, Quirós JR, Gonzalez CA, Sánchez MJ, Navarro C, Barricarte A, Dorronsoro M, Khaw KT, Wareham NJ, Crowe FL, Key TJ, Trichopoulou A, Lagiou P, Bamia C, Masala G, Vineis P, Tumino R, Sieri S, Panico S, May AM, Bueno-de-Mesquita HB, Büchner FL, Wirfält E, Manjer J, Johansson I, Hallmans G, Skeie G, Benjaminsen Borch K, Parr CL, Riboli E, Norat T (2012) Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study. Am J Clin Nutr 96(1):150–163. https://doi.org/10.3945/ajcn.111.031674CrossRefPubMed

34.

Zhang CX, Pan MX, Li B, Wang L, Mo XF, Chen YM, Lin FY, Ho SC (2013) Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case-control study in China. Cancer Sci 104(2):250–258. https://doi.org/10.1111/cas.12064CrossRefPubMed

35.

Cho E, Holmes MD, Hankinson SE, Willett WC (2010) Choline and betaine intake and risk of breast cancer among post-menopausal women. Br J Cancer 102(3):489–494. https://doi.org/10.1038/sj.bjc.6605510CrossRefPubMedPubMedCentral

36.

Ying J, Rahbar MH, Hallman DM, Hernandez LM, Spitz MR, Forman MR, Gorlova OY (2013) Associations between dietary intake of choline and betaine and lung cancer risk. PLoS ONE 8(2):e54561. https://doi.org/10.1371/journal.pone.0054561CrossRefPubMedPubMedCentral

37.

Kotsopoulos J, Hankinson SE, Tworoger SS (2010) Dietary betaine and choline intake are not associated with risk of epithelial ovarian cancer. Eur J Clin Nutr 64(1):111–114. https://doi.org/10.1038/ejcn.2009.109CrossRefPubMed

38.

Lee JE, Giovannucci E, Fuchs CS, Willett WC, Zeisel SH, Cho E (2010) Choline and betaine intake and the risk of colorectal cancer in men. Cancer Epidemiol Biomarkers Prev 19(3):884–887. https://doi.org/10.1158/1055-9965.EPI-09-1295CrossRefPubMedPubMedCentral

39.

Lu MS, Fang YJ, Pan ZZ, Zhong X, Zheng MC, Chen YM, Zhang CX (2015) Choline and betaine intake and colorectal cancer risk in Chinese population: a case-control study. PLoS ONE 10(3):e0118661. https://doi.org/10.1371/journal.pone.0118661CrossRefPubMedPubMedCentral

40.

Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Stabler SP, Allen RH, Caudill MA (2012) Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr 95(5):1060–1071. https://doi.org/10.3945/ajcn.111.022772CrossRefPubMed

41.

Myte R, Gylling B, Schneede J, Ueland PM, Häggström J, Hultdin J, Hallmans G, Johansson I, Palmqvist R, Van Guelpen B (2016) Components of one-carbon Metabolism Other than Folate and Colorectal Cancer Risk. Epidemiology 27(6):787–796. https://doi.org/10.1097/EDE.0000000000000529CrossRefPubMed

42.

Bao Q, He BS, Chen LP, Gu L, Nie ZL, Wang SK (2012) Correlation between polymorphism in the promoter of DNA methyltransferase-3B and the risk of colorectal cancer. Zhonghua Yu Fang Yi Xue Za Zhi 46(1):53–57 PMID: 22490141PubMed

43.

da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH (2006) Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr 84:88–94. https://doi.org/10.1093/ajcn/84.1.88CrossRefPubMed

44.

Mokarram P, Naghibalhossaini F, Firoozi MS, Hosseini SV, Izadpanah A, Salahi H, Malek-Hosseini SA, Talei A, Mojallal M (2008) Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status. World J Gastroenterol 14(23):3662–3671. https://doi.org/10.3748/wjg.14.3662CrossRefPubMedPubMedCentral

45.

Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113. https://doi.org/10.1038/ng0595-111CrossRefPubMed

46.

Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R (1996) Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 94(10):2410–2416. https://doi.org/10.1161/01.cir.94.10.2410CrossRefPubMed

47.

Razzak AA, Oxentenko AS, Vierkant RA, Tillmans LS, Wang AH, Weisenberger DJ, Laird PW, Lynch CF, Anderson KE, French AJ, Haile RW, Harnack LJ, Potter JD, Slager SL, Smyrk TC, Thibodeau SN, Cerhan JR, Limburg PJ (2012) Associations between intake of folate and related micronutrients with molecularly defined colorectal cancer risks in the Iowa women’s Health Study. Nutr Cancer 64(7):899–910. https://doi.org/10.1080/01635581.2012.714833CrossRefPubMedPubMedCentral

48.

Panprathip P, Petmitr S, Tungtrongchitr R, Kaewkungwal J, Kwanbunjan K (2019) Low folate status, and MTHFR 677C > T and MTR 2756A > G polymorphisms associated with colorectal cancer risk in Thais: a case-control study. Nutr Res 72:80–91. https://doi.org/10.1016/j.nutres.2019.10.008CrossRefPubMed

49.

Castelló A, Amiano P, Fernández de Larrea N, Martín V, Alonso MH, Castaño-Vinyals G, Pérez-Gómez B, Olmedo-Requena R, Guevara M, Fernandez-Tardon G, Dierssen-Sotos T, Llorens-Ivorra C, Huerta JM, Capelo R, Fernández-Villa T, Díez-Villanueva A, Urtiaga C, Castilla J, Jiménez-Moleón JJ, Moreno V, Dávila-Batista V, Kogevinas M, Aragonés N, Pollán M (2019) MCC-Spain researchers. Low adherence to the western and high adherence to the Mediterranean dietary patterns could prevent colorectal cancer. Eur J Nutr 58(4):1495–1505. https://doi.org/10.1007/s00394-018-1674-5CrossRefPubMed

50.

Feldblyum IV, Alyeva MK, Markovich NI (2016) The association between diet and the probability of colorectal cancer among the population of Perm Krai: epidemiological study. Vopr Pitan 85(5):60–67 PMID: 29381303PubMed

51.

Vereecken CA, Covents M, Sichert-Hellert W, Alvira JM, Le Donne C, De Henauw S, De Vriendt T, Phillipp MK, Béghin L, Manios Y, Hallström L, Poortvliet E, Matthys C, Plada M, Nagy E, Moreno LA, HELENA Study Group (2008) Development and evaluation of a self-administered computerized 24-h dietary recall method for adolescents in Europe. Int J Obes (Lond) 32(Suppl 5):S26–34. https://doi.org/10.1038/ijo.2008.180CrossRefPubMed

52.

Anderson AS, Steele R, Coyle J (2013) Lifestyle issues for colorectal cancer survivors–perceived needs, beliefs and opportunities. Support Care Cancer 21(1):35–42. https://doi.org/10.1007/s00520-012-1487-7CrossRefPubMed

53.

Berstad P, Løberg M, Larsen IK, Kalager M, Holme Ø, Botteri E, Bretthauer M, Hoff G (2015) Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial. Gut 64(8):1268–1276. https://doi.org/10.1136/gutjnl-2014-307376CrossRefPubMed

Title: Interactions between folate metabolism-related nutrients and polymorphisms on colorectal cancer risk: a case-control study in the Basque country
Authors: Sara Corchero-Palacios
Iker Alegria-Lertxundi
Marian M. de Pancorbo
Marta Arroyo-Izaga
Publication date: 23-04-2024
Publisher: Springer Berlin Heidelberg
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: European Journal of Nutrition
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-024-03371-5

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Interactions between folate metabolism-related nutrients and polymorphisms on colorectal cancer risk: a case-control study in the Basque country

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page