The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review

Marta Puzzono, Alessandro Mannucci, Simone Grannò, Raffaella Alessia Zuppardo, Andrea Galli, Silvio Danese, Giulia Martina Cavestro, Marta Puzzono, Alessandro Mannucci, Simone Grannò, Raffaella Alessia Zuppardo, Andrea Galli, Silvio Danese, Giulia Martina Cavestro

Abstract

The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs' exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.

Keywords: LINE-1; antibiotics; colorectal neoplasia; epigenetics; microbiota; obesity; risk factors; smoking; young.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart showing screening and inclusion of the eligible studies.
Figure 2
Figure 2
Protective and deleterious effects of diet in early-onset colorectal cancer. eoCRC—early-onset colorectal cancer; Met–meta-analysis; OR—odds ratio; RR—relative risk; SSB—sugar-sweetened beverage. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 3
Figure 3
Deleterious effects of alcohol in early-onset colorectal cancer. eoCRC—early-onset colorectal cancer; Met—meta-analysis; OR—odds ratio; RR—relative risk. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 4
Figure 4
Protective and deleterious effects of physical activity in early-onset colorectal cancer. eoCRC—early-onset colorectal cancer; OR—odds ratio; PA—physical activity; RR—relative risk. * p < 0.05; ** p < 0.01.
Figure 5
Figure 5
Protective and deleterious effects of obesity in early-onset colorectal cancer. AO—abdominal obesity; BMI—Body mass index; eoCRC—early-onset colorectal cancer; Met—meta-analysis; OR—odds ratio; RR—relative risk; SSB—sugar-sweetened beverage; WG—weight gain. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 6
Figure 6
Protective and deleterious effects of smoking in early-onset colorectal cancer. eoCRC—early-onset colorectal cancer; Met—meta-analysis; NFS—not further specified; OR—odds ratio; RR—relative risk. * p < 0.05; *** p < 0.001.

References

    1. Ahnen D.J., Wade S.W., Jones W.F., Sifri R., Mendoza Silveiras J., Greenamyer J., Guiffre S., Axilbund J., Spiegel A., You Y.N. The increasing incidence of young-onset colorectal cancer: A call to action. Mayo Clin. Proc. 2014;89:216–224. doi: 10.1016/j.mayocp.2013.09.006.
    1. Chang D.T., Pai R.K., Rybicki L.A., Dimaio M.A., Limaye M., Jayachandran P., Koong A.C., Kunz P.A., Fisher G.A., Ford J.M., et al. Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: An adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features. Mod. Pathol. 2012;25:1128–1139. doi: 10.1038/modpathol.2012.61.
    1. Araghi M., Soerjomataram I., Bardot A., Ferlay J., Cabasag C.J., Morrison D.S., De P., Tervonen H., Walsh P.M., Bucher O., et al. Changes in colorectal cancer incidence in seven high-income countries: A population-based study. Lancet Gastroenterol. Hepatol. 2019;4:511–518. doi: 10.1016/S2468-1253(19)30147-5.
    1. Russo A., Andreano A., Sartore-Bianchi A., Mauri G., Decarli A., Siena S. Increased incidence of colon cancer among individuals younger than 50 years: A 17 years analysis from the cancer registry of the municipality of Milan, Italy. Cancer Epidemiol. 2019;60:134–140. doi: 10.1016/j.canep.2019.03.015.
    1. Siegel R.L., Torre L.A., Soerjomataram I., Hayes R.B., Bray F., Weber T.K., Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019;68:2179–2185. doi: 10.1136/gutjnl-2019-319511.
    1. Vuik F.E., Nieuwenburg S.A., Bardou M., Lansdorp-Vogelaar I., Dinis-Ribeiro M., Bento M.J., Zadnik V., Pellise M., Esteban L., Kaminski M.F., et al. Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years. Gut. 2019;68:1820–1826. doi: 10.1136/gutjnl-2018-317592.
    1. Zorzi M., Dal Maso L., Francisci S., Buzzoni C., Rugge M., Guzzinati S., Group A.W. Trends of colorectal cancer incidence and mortality rates from 2003 to 2014 in Italy. Tumori. 2019;105:417–426. doi: 10.1177/0300891619838336.
    1. Zorzi M., Cavestro G.M., Guzzinati S., Dal Maso L., Rugge M., Group A.W. Decline in the incidence of colorectal cancer and the associated mortality in young Italian adults. Gut. 2020;69:1902–1903. doi: 10.1136/gutjnl-2019-320406.
    1. Stoffel E.M., Murphy C.C. Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology. 2020;158:341–353. doi: 10.1053/j.gastro.2019.07.055.
    1. Yeo H., Betel D., Abelson J.S., Zheng X.E., Yantiss R., Shah M.A. Early-onset colorectal cancer is distinct from traditional colorectal cancer. Clin. Colorectal Cancer. 2017;16:293–299. doi: 10.1016/j.clcc.2017.06.002.
    1. Di Leo M., Zuppardo R.A., Puzzono M., Ditonno I., Mannucci A., Antoci G., Russo Raucci A., Patricelli M.G., Elmore U., Tamburini A.M., et al. Risk factors and clinical characteristics of early-onset colorectal cancer vs. late-onset colorectal cancer: A case-case study. Eur. J. Gastroenterol. Hepatol. 2020;33:1153–1160. doi: 10.1097/MEG.0000000000002000.
    1. Yeo S., Chew M., Koh P., Tang C. Young colorectal carcinoma patients do not have a poorer prognosis: A comparative review of 2426 cases. Tech. Coloproctol. 2013;17:653–661. doi: 10.1007/s10151-013-0977-z.
    1. Cavestro G.M., Mannucci A., Zuppardo R.A., Di Leo M., Stoffel E., Tonon G. Early onset sporadic colorectal cancer: Worrisome trends and oncogenic features. Dig. Liver Dis. 2018;50:521–532. doi: 10.1016/j.dld.2018.02.009.
    1. Stoffel E.M., Koeppe E., Everett J., Ulintz P., Kiel M., Osborne J., Williams L., Hanson K., Gruber S.B., Rozek L.S. Germline Genetic Features of Young Individuals with Colorectal Cancer. Gastroenterology. 2018;154:897–905. doi: 10.1053/j.gastro.2017.11.004.
    1. Pearlman R., Frankel W.L., Swanson B., Zhao W., Yilmaz A., Miller K., Bacher J., Bigley C., Nelsen L., Goodfellow P.J. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 2017;3:464–471. doi: 10.1001/jamaoncol.2016.5194.
    1. Aune D., Lau R., Chan D.S., Vieira R., Greenwood D.C., Kampman E., Norat T. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology. 2011;141:106–118. doi: 10.1053/j.gastro.2011.04.013.
    1. Feng Y.L., Shu L., Zheng P.F., Zhang X.Y., Si C.J., Yu X.L., Gao W., Zhang L. Dietary patterns and colorectal cancer risk: A meta-analysis. Eur. J. Cancer Prev. 2017;26:201–211. doi: 10.1097/CEJ.0000000000000245.
    1. Barrubés L., Babio N., Becerra-Tomás N., Rosique-Esteban N., Salas-Salvadó J. Association between dairy product consumption and colorectal cancer risk in adults: A systematic review and meta-analysis of epidemiologic studies. Adv. Nutr. 2019;10:S190–S211. doi: 10.1093/advances/nmy114.
    1. Castelló A., Amiano P., de Larrea N.F., Martín V., Alonso M.H., Castaño-Vinyals G., Pérez-Gómez B., Olmedo-Requena R., Guevara M., Fernandez-Tardon G. Low adherence to the western and high adherence to the mediterranean dietary patterns could prevent colorectal cancer. Eur. J. Nutr. 2019;58:1495–1505. doi: 10.1007/s00394-018-1674-5.
    1. Keum N., Giovannucci E. Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat. Rev. Gastroenterol. Hepatol. 2019;16:713–732. doi: 10.1038/s41575-019-0189-8.
    1. Petimar J., Smith-Warner S.A., Fung T.T., Rosner B., Chan A.T., Hu F.B., Giovannucci E.L., Tabung F.K. Recommendation-based dietary indexes and risk of colorectal cancer in the Nurses’ Health Study and Health Professionals Follow-up Study. Am. J. Clin. Nutr. 2018;108:1092–1103. doi: 10.1093/ajcn/nqy171.
    1. Bradbury K.E., Murphy N., Key T.J. Diet and colorectal cancer in UK Biobank: A prospective study. Int. J. Epidemiol. 2020;49:246–258. doi: 10.1093/ije/dyz064.
    1. Chapelle N., Martel M., Toes-Zoutendijk E., Barkun A.N., Bardou M. Recent advances in clinical practice: Colorectal cancer chemoprevention in the average-risk population. Gut. 2020;69:2244–2255. doi: 10.1136/gutjnl-2020-320990.
    1. Wang L., Lo C.H., He X., Hang D., Wang M., Wu K., Chan A.T., Ogino S., Giovannucci E.L., Song M. Risk Factor Profiles Differ for Cancers of Different Regions of the Colorectum. Gastroenterology. 2020;159:241–256. doi: 10.1053/j.gastro.2020.03.054.
    1. Zhong Y., Zhu Y., Li Q., Wang F., Ge X., Zhou G., Miao L. Association between Mediterranean diet adherence and colorectal cancer: A dose-response meta-analysis. Am. J. Clin. Nutr. 2020;111:1214–1225. doi: 10.1093/ajcn/nqaa083.
    1. Kim J.Y., Jung Y.S., Park J.H., Kim H.J., Cho Y.K., Sohn C.I., Jeon W.K., Kim B.I., Choi K.Y., Park D.I. Different risk factors for advanced colorectal neoplasm in young adults. World J. Gastroenterol. 2016;22:3611–3620. doi: 10.3748/wjg.v22.i13.3611.
    1. Kim N.H., Jung Y.S., Yang H.J., Park S.K., Park J.H., Park D.I., Sohn C.I. Prevalence of and Risk Factors for Colorectal Neoplasia in Asymptomatic Young Adults (20–39 Years Old) Clin. Gastroenterol. Hepatol. 2019;17:115–122. doi: 10.1016/j.cgh.2018.07.011.
    1. Nguyen L.H., Liu P.H., Zheng X., Keum N., Zong X., Li X., Wu K., Fuchs C.S., Ogino S., Ng K., et al. Sedentary Behaviors, TV Viewing Time, and Risk of Young-Onset Colorectal Cancer. JNCI Cancer Spectr. 2018;2:pky073. doi: 10.1093/jncics/pky073.
    1. Rosato V., Bosetti C., Levi F., Polesel J., Zucchetto A., Negri E., La Vecchia C. Risk factors for young-onset colorectal cancer. Cancer Causes Control. 2013;24:335–341. doi: 10.1007/s10552-012-0119-3.
    1. Gausman V., Dornblaser D., Anand S., Hayes R.B., O’Connell K., Du M., Liang P.S. Risk Factors Associated With Early-Onset Colorectal Cancer. Clin. Gastroenterol. Hepatol. 2020;18:2752–2759. doi: 10.1016/j.cgh.2019.10.009.
    1. Liu P.-H., Wu K., Ng K., Zauber A.G., Nguyen L.H., Song M., He X., Fuchs C.S., Ogino S., Willett W.C. Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncol. 2019;5:37–44. doi: 10.1001/jamaoncol.2018.4280.
    1. Low E.E., Demb J., Liu L., Earles A., Bustamante R., Williams C.D., Provenzale D., Kaltenbach T., Gawron A.J., Martinez M.E., et al. Risk Factors for Early-Onset Colorectal Cancer. Gastroenterology. 2020;159:492–501. doi: 10.1053/j.gastro.2020.01.004.
    1. Zheng X., Hur J., Nguyen L.H., Liu J., Song M., Wu K., Smith-Warner S.A., Ogino S., Willett W.C., Chan A.T., et al. Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer. J. Natl. Cancer Inst. 2020;113:543–552. doi: 10.1093/jnci/djaa164.
    1. Boucher B., Cotterchio M., Kreiger N., Nadalin V., Block T., Block G. Validity and reliability of the Block98 food-frequency questionnaire in a sample of Canadian women. Public Health Nutr. 2006;9:84–93. doi: 10.1079/PHN2005763.
    1. Decarli A., Franceschi S., Ferraroni M., Gnagnarella P., Parpinel M.T., La Vecchia C., Negri E., Salvini S., Falcini F., Giacosa A. Validation of a food-frequency questionnaire to assess dietary intakes in cancer studies in Italy. Results for specific nutrients. Ann. Epidemiol. 1996;6:110–118. doi: 10.1016/1047-2797(95)00129-8.
    1. Huxley R.R., Ansary-Moghaddam A., Clifton P., Czernichow S., Parr C.L., Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: A quantitative overview of the epidemiological evidence. Int. J. Cancer. 2009;125:171–180. doi: 10.1002/ijc.24343.
    1. Imperiale T.F., Kahi C.J., Stuart J.S., Qi R., Born L.J., Glowinski E.A., Rex D.K. Risk factors for advanced sporadic colorectal neoplasia in persons younger than age 50. Cancer Detect. Prev. 2008;32:33–38. doi: 10.1016/j.cdp.2008.01.003.
    1. Trock B., Lanza E., Greenwald P. Dietary fiber, vegetables, and colon cancer: Critical review and meta-analyses of the epidemiologic evidence. J. Natl. Cancer Inst. 1990;82:650–661. doi: 10.1093/jnci/82.8.650.
    1. Tse G., Eslick G.D. Cruciferous vegetables and risk of colorectal neoplasms: A systematic review and meta-analysis. Nutr. Cancer. 2014;66:128–139. doi: 10.1080/01635581.2014.852686.
    1. Vieira A.R., Abar L., Chan D.S.M., Vingeliene S., Polemiti E., Stevens C., Greenwood D., Norat T. Foods and beverages and colorectal cancer risk: A systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Ann. Oncol. 2017;28:1788–1802. doi: 10.1093/annonc/mdx171.
    1. Woo H.D., Park S., Oh K., Kim H.J., Shin H.R., Moon H.K., Kim J. Diet and cancer risk in the Korean population: A meta-analysis. Asian Pac. J. Cancer Prev. 2014;15:8509–8519. doi: 10.7314/APJCP.2014.15.19.8509.
    1. Wu Q.J., Yang Y., Vogtmann E., Wang J., Han L.H., Li H.L., Xiang Y.B. Cruciferous vegetables intake and the risk of colorectal cancer: A meta-analysis of observational studies. Ann. Oncol. 2013;24:1079–1087. doi: 10.1093/annonc/mds601.
    1. Zhu B., Sun Y., Qi L., Zhong R., Miao X. Dietary legume consumption reduces risk of colorectal cancer: Evidence from a meta-analysis of cohort studies. Sci. Rep. 2015;5:8797. doi: 10.1038/srep08797.
    1. Kashino I., Mizoue T., Tanaka K., Tsuji I., Tamakoshi A., Matsuo K., Wakai K., Nagata C., Inoue M., Tsugane S. Vegetable consumption and colorectal cancer risk: An evaluation based on a systematic review and meta-analysis among the Japanese population. Jpn. J. Clin. Oncol. 2015;45:973–979. doi: 10.1093/jjco/hyv111.
    1. Geelen A., Schouten J.M., Kamphuis C., Stam B.E., Burema J., Renkema J.M., Bakker E.J., van’t Veer P., Kampman E. Fish consumption, n-3 fatty acids, and colorectal cancer: A meta-analysis of prospective cohort studies. Am. J. Epidemiol. 2007;166:1116–1125. doi: 10.1093/aje/kwm197.
    1. Pham N.M., Mizoue T., Tanaka K., Tsuji I., Tamakoshi A., Matsuo K., Wakai K., Nagata C., Inoue M., Tsugane S. Fish consumption and colorectal cancer risk: An evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn. J. Clin. Oncol. 2013;43:935–941. doi: 10.1093/jjco/hyt094.
    1. Shen X.J., Zhou J.D., Dong J.Y., Ding W.Q., Wu J.C. Dietary intake of n-3 fatty acids and colorectal cancer risk: A meta-analysis of data from 489 000 individuals. Br. J. Nutr. 2012;108:1550–1556. doi: 10.1017/S0007114512003546.
    1. Wu S., Feng B., Li K., Zhu X., Liang S., Liu X., Han S., Wang B., Wu K., Miao D., et al. Fish consumption and colorectal cancer risk in humans: A systematic review and meta-analysis. Am. J. Med. 2012;125:551–559. doi: 10.1016/j.amjmed.2012.01.022.
    1. Yu X.F., Zou J., Dong J. Fish consumption and risk of gastrointestinal cancers: A meta-analysis of cohort studies. World J. Gastroenterol. 2014;20:15398–15412. doi: 10.3748/wjg.v20.i41.15398.
    1. Phillips D.H., Grover P.L. Polycyclic hydrocarbon activation: Bay regions and beyond. Drug Metab. Rev. 1994;26:443–467. doi: 10.3109/03602539409029808.
    1. Song M., Chan A.T. Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention. Clin. Gastroenterol. Hepatol. 2019;17:275–289. doi: 10.1016/j.cgh.2018.07.012.
    1. Yang J., Yu J. The association of diet, gut microbiota and colorectal cancer: What we eat may imply what we get. Protein Cell. 2018;9:474–487. doi: 10.1007/s13238-018-0543-6.
    1. Cross A.J., Ferrucci L.M., Risch A., Graubard B.I., Ward M.H., Park Y., Hollenbeck A.R., Schatzkin A., Sinha R. A large prospective study of meat consumption and colorectal cancer risk: An investigation of potential mechanisms underlying this association. Cancer Res. 2010;70:2406–2414. doi: 10.1158/0008-5472.CAN-09-3929.
    1. Ferrucci L.M., Sinha R., Huang W.Y., Berndt S.I., Katki H.A., Schoen R.E., Hayes R.B., Cross A.J. Meat consumption and the risk of incident distal colon and rectal adenoma. Br. J. Cancer. 2012;106:608–616. doi: 10.1038/bjc.2011.549.
    1. Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly Y.M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341:569–573. doi: 10.1126/science.1241165.
    1. Donohoe D.R., Holley D., Collins L.B., Montgomery S.A., Whitmore A.C., Hillhouse A., Curry K.P., Renner S.W., Greenwalt A., Ryan E.P. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota-and butyrate-dependent manner. Cancer Discov. 2014;4:1387–1397. doi: 10.1158/-14-0501.
    1. Archambault A.N., Lin Y., Jeon J., Harrison T.A., Bishop D.T., Brenner H., Casey G., Chan A.T., Chang-Claude J., Figueiredo J.C., et al. Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer. JNCI Cancer Spectr. 2021;5:pkab029. doi: 10.1093/jncics/pkab029.
    1. Khan N.A., Hussain M., ur Rahman A., Farooqui W.A., Rasheed A., Memon A.S. Dietary Practices, Addictive Behavior and Bowel Habits and Risk of Early Onset Colorectal Cancer: A Case Control Study. Asian Pac. J. Cancer Prev. 2015;16:7967–7973. doi: 10.7314/APJCP.2015.16.17.7967.
    1. Chang V.C., Cotterchio M., De P., Tinmouth J. Risk factors for early-onset colorectal cancer: A population-based case-control study in Ontario, Canada. Cancer Causes Control. 2021;32:1063–1083. doi: 10.1007/s10552-021-01456-8.
    1. Tabung F.K., Brown L.S., Fung T.T. Dietary Patterns and Colorectal Cancer Risk: A Review of 17 Years of Evidence (2000–2016) Curr. Colorectal Cancer Rep. 2017;13:440–454. doi: 10.1007/s11888-017-0390-5.
    1. Garcia-Larsen V., Morton V., Norat T., Moreira A., Potts J.F., Reeves T., Bakolis I. Dietary patterns derived from principal component analysis (PCA) and risk of colorectal cancer: A systematic review and meta-analysis. Eur. J. Clin. Nutr. 2019;73:366–386. doi: 10.1038/s41430-018-0234-7.
    1. Nimptsch K., Malik V.S., Fung T.T., Pischon T., Hu F.B., Willett W.C., Fuchs C.S., Ogino S., Chan A.T., Giovannucci E., et al. Dietary patterns during high school and risk of colorectal adenoma in a cohort of middle-aged women. Int. J. Cancer. 2014;134:2458–2467. doi: 10.1002/ijc.28578.
    1. Jones P., Cade J.E., Evans C.E.L., Hancock N., Greenwood D.C. The Mediterranean diet and risk of colorectal cancer in the UK Women’s Cohort Study. Int. J. Epidemiol. 2017;46:1786–1796. doi: 10.1093/ije/dyx155.
    1. Agnoli C., Grioni S., Sieri S., Palli D., Masala G., Sacerdote C., Vineis P., Tumino R., Giurdanella M.C., Pala V., et al. Italian Mediterranean Index and risk of colorectal cancer in the Italian section of the EPIC cohort. Int. J. Cancer. 2013;132:1404–1411. doi: 10.1002/ijc.27740.
    1. Hur J., Otegbeye E., Joh H.K., Nimptsch K., Ng K., Ogino S., Meyerhardt J.A., Chan A.T., Willett W.C., Wu K., et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021;70:2330–2336. doi: 10.1136/gutjnl-2020-323450.
    1. Aune D., Lau R., Chan D.S.M., Vieira R., Greenwood D.C., Kampman E., Norat T. Dairy products and colorectal cancer risk: A systematic review and meta-analysis of cohort studies. Ann. Oncol. 2012;23:37–45. doi: 10.1093/annonc/mdr269.
    1. Ralston R.A., Truby H., Palermo C.E., Walker K.Z. Colorectal cancer and nonfermented milk, solid cheese, and fermented milk consumption: A systematic review and meta-analysis of prospective studies. Crit. Rev. Food Sci. Nutr. 2014;54:1167–1179. doi: 10.1080/10408398.2011.629353.
    1. Keum N., Aune D., Greenwood D.C., Ju W., Giovannucci E.L. Calcium intake and colorectal cancer risk: Dose-response meta-analysis of prospective observational studies. Int. J. Cancer. 2014;135:1940–1948. doi: 10.1002/ijc.28840.
    1. Lamprecht S.A., Lipkin M. Cellular mechanisms of calcium and vitamin D in the inhibition of colorectal carcinogenesis. Ann. N. Y. Acad. Sci. 2001;952:73–87. doi: 10.1111/j.1749-6632.2001.tb02729.x.
    1. Syed A.R., Thakkar P., Horne Z.D., Abdul-Baki H., Kochhar G., Farah K., Thakkar S. Old vs new: Risk factors predicting early onset colorectal cancer. World J. Gastrointest. Oncol. 2019;11:1011–1020. doi: 10.4251/wjgo.v11.i11.1011.
    1. Bagnardi V., Blangiardo M., La Vecchia C., Corrao G. A meta-analysis of alcohol drinking and cancer risk. Br. J. Cancer. 2001;85:1700–1705. doi: 10.1054/bjoc.2001.2140.
    1. Bagnardi V., Rota M., Botteri E., Tramacere I., Islami F., Fedirko V., Scotti L., Jenab M., Turati F., Pasquali E., et al. Light alcohol drinking and cancer: A meta-analysis. Ann. Oncol. 2013;24:301–308. doi: 10.1093/annonc/mds337.
    1. Bagnardi V., Rota M., Botteri E., Tramacere I., Islami F., Fedirko V., Scotti L., Jenab M., Turati F., Pasquali E., et al. Alcohol consumption and site-specific cancer risk: A comprehensive dose-response meta-analysis. Br. J. Cancer. 2015;112:580–593. doi: 10.1038/bjc.2014.579.
    1. Corrao G., Bagnardi V., Zambon A., Arico S. Exploring the dose-response relationship between alcohol consumption and the risk of several alcohol-related conditions: A meta-analysis. Addiction. 1999;94:1551–1573. doi: 10.1046/j.1360-0443.1999.9410155111.x.
    1. Fedirko V., Tramacere I., Bagnardi V., Rota M., Scotti L., Islami F., Negri E., Straif K., Romieu I., La Vecchia C. Alcohol drinking and colorectal cancer risk: An overall and dose–response meta-analysis of published studies. Ann. Oncol. 2011;22:1958–1972. doi: 10.1093/annonc/mdq653.
    1. Longnecker M.P., Orza M.J., Adams M.E., Vioque J., Chalmers T.C. A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer. Cancer Causes Control. 1990;1:59–68. doi: 10.1007/BF00053184.
    1. Moskal A., Norat T., Ferrari P., Riboli E. Alcohol intake and colorectal cancer risk: A dose-response meta-analysis of published cohort studies. Int. J. Cancer. 2007;120:664–671. doi: 10.1002/ijc.22299.
    1. Wang Y., Duan H., Yang H., Lin J. A pooled analysis of alcohol intake and colorectal cancer. Int. J. Clin. Exp. Med. 2015;8:6878–6889.
    1. Zhang C., Zhong M. Consumption of beer and colorectal cancer incidence: A meta-analysis of observational studies. Cancer Causes Control. 2015;26:549–560. doi: 10.1007/s10552-015-0532-5.
    1. Breau G., Ellis U. Risk Factors Associated with Young-Onset Colorectal Adenomas and Cancer: A Systematic Review and Meta-Analysis of Observational Research. Cancer Control. 2020;27:1073274820976670. doi: 10.1177/1073274820976670.
    1. Kim J.Y., Choi S., Park T., Kim S.K., Jung Y.S., Park J.H., Kim H.J., Cho Y.K., Sohn C.I., Jeon W.K., et al. Development and validation of a scoring system for advanced colorectal neoplasm in young Korean subjects less than age 50 years. Intest. Res. 2019;17:253–264. doi: 10.5217/ir.2018.00062.
    1. Lee S.E., Jo H.B., Kwack W.G., Jeong Y.J., Yoon Y.J., Kang H.W. Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population. World J. Gastroenterol. 2016;22:2981–2992. doi: 10.3748/wjg.v22.i10.2981.
    1. O’Sullivan D.E., Sutherland R.L., Town S., Chow K., Fan J., Forbes N., Heitman S.J., Hilsden R.J., Brenner D.R. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol. 2021:S1542-3565(21)00087-2. doi: 10.1016/j.cgh.2021.01.037.
    1. Glover M., Mansoor E., Panhwar M., Parasa S., Cooper G.S. Epidemiology of Colorectal Cancer in Average Risk Adults 20–39 Years of Age: A Population-Based National Study. Dig. Dis. Sci. 2019;64:3602–3609. doi: 10.1007/s10620-019-05690-8.
    1. Bull-Otterson L., Feng W., Kirpich I., Wang Y., Qin X., Liu Y., Gobejishvili L., Joshi-Barve S., Ayvaz T., Petrosino J., et al. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment. PLoS ONE. 2013;8:e53028. doi: 10.1371/journal.pone.0053028.
    1. Mutlu E.A., Gillevet P.M., Rangwala H., Sikaroodi M., Naqvi A., Engen P.A., Kwasny M., Lau C.K., Keshavarzian A. Colonic microbiome is altered in alcoholism. Am. J. Physiol. Gastrointest. Liver Physiol. 2012;302:G966–G978. doi: 10.1152/ajpgi.00380.2011.
    1. Tsuruya A., Kuwahara A., Saito Y., Yamaguchi H., Tsubo T., Suga S., Inai M., Aoki Y., Takahashi S., Tsutsumi E., et al. Ecophysiological consequences of alcoholism on human gut microbiota: Implications for ethanol-related pathogenesis of colon cancer. Sci. Rep. 2016;6:27923. doi: 10.1038/srep27923.
    1. Yan A.W., Fouts D.E., Brandl J., Starkel P., Torralba M., Schott E., Tsukamoto H., Nelson K.E., Brenner D.A., Schnabl B. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology. 2011;53:96–105. doi: 10.1002/hep.24018.
    1. Tsuruya A., Kuwahara A., Saito Y., Yamaguchi H., Tenma N., Inai M., Takahashi S., Tsutsumi E., Suwa Y., Totsuka Y., et al. Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum. Alcohol Alcohol. 2016;51:395–401. doi: 10.1093/alcalc/agv135.
    1. Robsahm T.E., Aagnes B., Hjartaker A., Langseth H., Bray F.I., Larsen I.K. Body mass index, physical activity, and colorectal cancer by anatomical subsites: A systematic review and meta-analysis of cohort studies. Eur. J. Cancer Prev. 2013;22:492–505. doi: 10.1097/CEJ.0b013e328360f434.
    1. Slattery M.L. Physical activity and colorectal cancer. Sports Med. 2004;34:239–252. doi: 10.2165/00007256-200434040-00004.
    1. Bressa C., Bailén-Andrino M., Pérez-Santiago J., González-Soltero R., Pérez M., Montalvo-Lominchar M.G., Maté-Muñoz J.L., Domínguez R., Moreno D., Larrosa M. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS ONE. 2017;12:e0171352. doi: 10.1371/journal.pone.0171352.
    1. Mach N., Fuster-Botella D. Endurance exercise and gut microbiota: A review. J. Sport Health Sci. 2017;6:179–197. doi: 10.1016/j.jshs.2016.05.001.
    1. Evans C.C., LePard K.J., Kwak J.W., Stancukas M.C., Laskowski S., Dougherty J., Moulton L., Glawe A., Wang Y., Leone V., et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS ONE. 2014;9:e92193. doi: 10.1371/journal.pone.0092193.
    1. Matsumoto M., Inoue R., Tsukahara T., Ushida K., Chiji H., Matsubara N., Hara H. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem. 2008;72:572–576. doi: 10.1271/bbb.70474.
    1. Holowatyj A.N., Langston M.E., Han Y., Viskochil R., Perea J., Cao Y., Rogers C.R., Lieu C.H., Moore J.X. Community health behaviors and geographic variation in early-onset colorectal cancer survival among women. Clin. Transl. Gastroenterol. 2020;11:e00266. doi: 10.14309/ctg.0000000000000266.
    1. Esposito K., Chiodini P., Capuano A., Bellastella G., Maiorino M.I., Rafaniello C., Panagiotakos D.B., Giugliano D. Colorectal cancer association with metabolic syndrome and its components: A systematic review with meta-analysis. Endocrine. 2013;44:634–647. doi: 10.1007/s12020-013-9939-5.
    1. Esposito K., Chiodini P., Colao A., Lenzi A., Giugliano D. Metabolic syndrome and risk of cancer: A systematic review and meta-analysis. Diabetes Care. 2012;35:2402–2411. doi: 10.2337/dc12-0336.
    1. Khan M.T., Nieuwdorp M., Backhed F. Microbial modulation of insulin sensitivity. Cell Metab. 2014;20:753–760. doi: 10.1016/j.cmet.2014.07.006.
    1. Cani P.D., Jordan B.F. Gut microbiota-mediated inflammation in obesity: A link with gastrointestinal cancer. Nat. Rev. Gastroenterol. Hepatol. 2018;15:671–682. doi: 10.1038/s41575-018-0025-6.
    1. Li R., Grimm S.A., Chrysovergis K., Kosak J., Wang X., Du Y., Burkholder A., Janardhan K., Mav D., Shah R. Obesity, rather than diet, drives epigenomic alterations in colonic epithelium resembling cancer progression. Cell Metab. 2014;19:702–711. doi: 10.1016/j.cmet.2014.03.012.
    1. Li R., Grimm S.A., Mav D., Gu H., Djukovic D., Shah R., Merrick B.A., Raftery D., Wade P.A. Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer. Cell Rep. 2018;22:624–637. doi: 10.1016/j.celrep.2017.12.071.
    1. Sanford N.N., Giovannucci E.L., Ahn C., Dee E.C., Mahal B.A. Obesity and younger versus older onset colorectal cancer in the United States, 1998–2017. J. Gastrointest. Oncol. 2020;11:121–126. doi: 10.21037/jgo.2019.12.07.
    1. Hussan H., Patel A., Le Roux M., Cruz-Monserrate Z., Porter K., Clinton S.K., Carethers J.M., Courneya K.S. Rising Incidence of Colorectal Cancer in Young Adults Corresponds with Increasing Surgical Resections in Obese Patients. Clin. Transl. Gastroenterol. 2020;11:e00160. doi: 10.14309/ctg.0000000000000160.
    1. Chen H., Zheng X., Zong X., Li Z., Li N., Hur J., Fritz C.D., Chapman W., Jr., Nickel K.B., Tipping A., et al. Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer. Gut. 2020;70:1147–1154. doi: 10.1136/gutjnl-2020-321661.
    1. Jung Y.S., Park C.H., Kim N.H., Lee M.Y., Park D.I. Impact of Age on the Risk of Advanced Colorectal Neoplasia in a Young Population: An Analysis Using the Predicted Probability Model. Dig. Dis. Sci. 2017;62:2518–2525. doi: 10.1007/s10620-017-4683-y.
    1. Li H., Boakye D., Chen X., Hoffmeister M., Brenner H. Association of Body Mass Index with Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis. Am. J. Gastroenterol. 2021;116:2173–2183. doi: 10.14309/ajg.0000000000001393.
    1. Dash C., Yu J., Nomura S., Lu J., Rosenberg L., Palmer J.R., Adams-Campbell L.L. Obesity is an initiator of colon adenomas but not a promoter of colorectal cancer in the Black Women’s Health Study. Cancer Causes Control. 2020;31:291–302. doi: 10.1007/s10552-020-01283-3.
    1. Elangovan A., Skeans J., Landsman M., Ali S.M.J., Elangovan A.G., Kaelber D.C., Sandhu D.S., Cooper G.S. Colorectal Cancer, Age, and Obesity-Related Comorbidities: A Large Database Study. Dig. Dis. Sci. 2021;66:3156–3163. doi: 10.1007/s10620-020-06602-x.
    1. Kantor E.D., Udumyan R., Signorello L.B., Giovannucci E.L., Montgomery S., Fall K. Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk. Gut. 2016;65:1289–1295. doi: 10.1136/gutjnl-2014-309007.
    1. Levi F., Pasche C., La Vecchia C., Lucchini F., Franceschi S. Food groups and colorectal cancer risk. Br. J. Cancer. 1999;79:1283–1287. doi: 10.1038/sj.bjc.6690206.
    1. Moore L.L., Bradlee M.L., Singer M.R., Splansky G.L., Proctor M.H., Ellison R.C., Kreger B.E. BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int. J. Obes. Relat. Metab. Disord. 2004;28:559–567. doi: 10.1038/sj.ijo.0802606.
    1. Himbert C., Figueiredo J.C., Shibata D., Ose J., Lin T., Huang L.C., Peoples A.R., Scaife C.L., Pickron B., Lambert L., et al. Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset. Cancers. 2021;13:3817. doi: 10.3390/cancers13153817.
    1. Botteri E., Borroni E., Sloan E.K., Bagnardi V., Bosetti C., Peveri G., Santucci C., Specchia C., van den Brandt P., Gallus S., et al. Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis. Am. J. Gastroenterol. 2020;115:1940–1949. doi: 10.14309/ajg.0000000000000803.
    1. Botteri E., Iodice S., Bagnardi V., Raimondi S., Lowenfels A.B., Maisonneuve P. Smoking and colorectal cancer: A meta-analysis. JAMA. 2008;300:2765–2778. doi: 10.1001/jama.2008.839.
    1. Liang P.S., Chen T.Y., Giovannucci E. Cigarette smoking and colorectal cancer incidence and mortality: Systematic review and meta-analysis. Int. J. Cancer. 2009;124:2406–2415. doi: 10.1002/ijc.24191.
    1. Agazzi S., Lenti M.V., Klersy C., Strada E., Pozzi L., Rovedatti L., Bardone M., Mauro A., Costetti M., Costa S., et al. Incidence and risk factors for preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 referred for colonoscopy. Eur. J. Intern. Med. 2021;87:36–43. doi: 10.1016/j.ejim.2021.02.008.
    1. Krigel A., Zhou M., Terry M.B., Kastrinos F., Lebwohl B. Symptoms and demographic factors associated with early-onset colorectal neoplasia among individuals undergoing diagnostic colonoscopy. Eur. J. Gastroenterol. Hepatol. 2020;32:821–826. doi: 10.1097/MEG.0000000000001720.
    1. Schumacher A.J., Chen Q., Attaluri V., McLemore E.C., Chao C.R. Metabolic Risk Factors Associated with Early-Onset Colorectal Adenocarcinoma: A Case-Control Study at Kaiser Permanente Southern California. Cancer Epidemiol. Biomark. Prev. 2021;30:1792–1798. doi: 10.1158/1055-9965.EPI-20-1127.
    1. Baars J., Kuipers E., Van Haastert M., Nicolaï J., Poen A., Van der Woude C. Age at diagnosis of inflammatory bowel disease influences early development of colorectal cancer in inflammatory bowel disease patients: A nationwide, long-term survey. J. Gastroenterol. 2012;47:1308–1322. doi: 10.1007/s00535-012-0603-2.
    1. Monahan K.J., Bradshaw N., Dolwani S., Desouza B., Dunlop M.G., East J.E., Ilyas M., Kaur A., Lalloo F., Latchford A., et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG) Gut. 2020;69:411–444. doi: 10.1136/gutjnl-2019-319915.
    1. Seppala T.T., Latchford A., Negoi I., Sampaio Soares A., Jimenez-Rodriguez R., Sanchez-Guillen L., Evans D.G., Ryan N., Crosbie E.J., Dominguez-Valentin M., et al. European guidelines from the EHTG and ESCP for Lynch syndrome: An updated third edition of the Mallorca guidelines based on gene and gender. Br. J. Surg. 2021;108:484–498. doi: 10.1002/bjs.11902.
    1. Van Leerdam M.E., Roos V.H., van Hooft J.E., Balaguer F., Dekker E., Kaminski M.F., Latchford A., Neumann H., Ricciardiello L., Rupinska M., et al. Endoscopic management of Lynch syndrome and of familial risk of colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2019;51:1082–1093. doi: 10.1055/a-1016-4977.
    1. Van Leerdam M.E., Roos V.H., van Hooft J.E., Dekker E., Jover R., Kaminski M.F., Latchford A., Neumann H., Pellise M., Saurin J.C., et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2019;51:877–895. doi: 10.1055/a-0965-0605.
    1. Wagner A., Zandanell S., Kiesslich T., Neureiter D., Klieser E., Holzinger J., Berr F. Systematic Review on Optical Diagnosis of Early Gastrointestinal Neoplasia. J. Clin. Med. 2021;10:2794. doi: 10.3390/jcm10132794.
    1. Wijnands A.M., Mahmoud R., Lutgens M., Oldenburg B. Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives. Eur. J. Intern. Med. 2021;93:35–41. doi: 10.1016/j.ejim.2021.08.010.
    1. Yang J., Gurudu S.R., Koptiuch C., Agrawal D., Buxbaum J.L., Abbas Fehmi S.M., Fishman D.S., Khashab M.A., Jamil L.H., Jue T.L., et al. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes. Gastrointest. Endosc. 2020;91:963–982. doi: 10.1016/j.gie.2020.01.028.
    1. Nimptsch K., Wu K. Is timing important? The role of diet and lifestyle during early life on colorectal neoplasia. Curr. Colorectal Cancer Rep. 2018;14:1–11. doi: 10.1007/s11888-018-0396-7.
    1. Wolff E.M., Byun H.M., Han H.F., Sharma S., Nichols P.W., Siegmund K.D., Yang A.S., Jones P.A., Liang G. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet. 2010;6:e1000917. doi: 10.1371/journal.pgen.1000917.
    1. Goelz S.E., Vogelstein B., Hamilton S.R., Feinberg A.P. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science. 1985;228:187–190. doi: 10.1126/science.2579435.
    1. Jones P.A., Baylin S.B. The epigenomics of cancer. Cell. 2007;128:683–692. doi: 10.1016/j.cell.2007.01.029.
    1. Mas S., Lafuente M.J., Crescenti A., Trias M., Ballesta A., Molina R., Zheng S., Wiencke J.K., Lafuente A. Lower specific micronutrient intake in colorectal cancer patients with tumors presenting promoter hypermethylation in p16INK4a, p14ARF and hMLH1. Anticancer Res. 2007;27:1151–1156.
    1. Van Engeland M., Weijenberg M.P., Roemen G.M., Brink M., de Bruïne A.P., Goldbohm R.A., van den Brandt P.A., Baylin S.B., de Goeij A.F., Herman J.G. Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: The Netherlands cohort study on diet and cancer. Cancer Res. 2003;63:3133–3137.
    1. Schernhammer E.S., Giovannucci E., Kawasaki T., Rosner B., Fuchs C.S., Ogino S. Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut. 2010;59:794–799. doi: 10.1136/gut.2009.183707.
    1. Gogna P., O’Sullivan D.E., King W.D. The effect of inflammation-related lifestyle exposures and interactions with gene variants on long interspersed nuclear element-1 DNA methylation. Epigenomics. 2018;10:785–796. doi: 10.2217/epi-2017-0164.
    1. Martin E.M., Fry R.C. Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations. Annu. Rev. Public Health. 2018;39:309–333. doi: 10.1146/annurev-publhealth-040617-014629.
    1. Antelo M., Balaguer F., Shia J., Shen Y., Hur K., Moreira L., Cuatrecasas M., Bujanda L., Giraldez M.D., Takahashi M., et al. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS ONE. 2012;7:e45357. doi: 10.1371/journal.pone.0045357.
    1. Akimoto N., Zhao M., Ugai T., Zhong R., Lau M.C., Fujiyoshi K., Kishikawa J., Haruki K., Arima K., Twombly T.S., et al. Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis. Cancers. 2021;13:2016. doi: 10.3390/cancers13092016.
    1. Kaiko G.E., Ryu S.H., Koues O.I., Collins P.L., Solnica-Krezel L., Pearce E.J., Pearce E.L., Oltz E.M., Stappenbeck T.S. The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. Cell. 2016;165:1708–1720. doi: 10.1016/j.cell.2016.05.018.
    1. Daly K., Shirazi-Beechey S.P. Microarray analysis of butyrate regulated genes in colonic epithelial cells. DNA Cell Biol. 2006;25:49–62. doi: 10.1089/dna.2006.25.49.
    1. Davie J.R. Inhibition of histone deacetylase activity by butyrate. J. Nutr. 2003;133:S2485–S2493. doi: 10.1093/jn/133.7.2485S.
    1. Hu S., Dong T.S., Dalal S.R., Wu F., Bissonnette M., Kwon J.H., Chang E.B. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer. PLoS ONE. 2011;6:e16221. doi: 10.1371/journal.pone.0016221.
    1. Ali S.R., Orang A., Marri S., McKinnon R.A., Meech R., Michael M.Z. Integrative Transcriptomic Network Analysis of Butyrate Treated Colorectal Cancer Cells. Cancers. 2021;13:636. doi: 10.3390/cancers13040636.
    1. Humphreys K.J., Cobiac L., Le Leu R.K., Van der Hoek M.B., Michael M.Z. Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR-17-92 cluster. Mol. Carcinog. 2013;52:459–474. doi: 10.1002/mc.21879.
    1. Bhuyan R., Bagchi A. Prediction of the differentially expressed circRNAs to decipher their roles in the onset of human colorectal cancers. Gene. 2020;762:145035. doi: 10.1016/j.gene.2020.145035.
    1. Ding L., Lan Z., Xiong X., Ao H., Feng Y., Gu H., Yu M., Cui Q. The Dual Role of MicroRNAs in Colorectal Cancer Progression. Int. J. Mol. Sci. 2018;19:2791. doi: 10.3390/ijms19092791.
    1. Vafaee F., Diakos C., Kirschner M.B., Reid G., Michael M.Z., Horvath L.G., Alinejad-Rokny H., Cheng Z.J., Kuncic Z., Clarke S. A data-driven, knowledge-based approach to biomarker discovery: Application to circulating microRNA markers of colorectal cancer prognosis. NPJ Syst. Biol. Appl. 2018;4:20. doi: 10.1038/s41540-018-0056-1.
    1. Xiong G., Zhang J., Zhang Y., Pang X., Wang B., Zhang Y. Circular RNA_0074027 participates in cell proliferation, apoptosis and metastasis of colorectal cancer cells through regulation of miR5253p. Mol. Med. Rep. 2021;23:1–11. doi: 10.3892/mmr.2021.11963.
    1. Angius A., Pira G., Scanu A.M., Uva P., Sotgiu G., Saderi L., Manca A., Serra C., Uleri E., Piu C., et al. MicroRNA-425-5p Expression Affects BRAF/RAS/MAPK Pathways in Colorectal Cancers. Int. J. Med. Sci. 2019;16:1480–1491. doi: 10.7150/ijms.35269.
    1. Du F., Cao T., Xie H., Li T., Sun L., Liu H., Guo H., Wang X., Liu Q., Kim T., et al. KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling. Theranostics. 2020;10:7335–7350. doi: 10.7150/thno.45971.
    1. Senaldi L., Smith-Raska M. Evidence for germline non-genetic inheritance of human phenotypes and diseases. Clin. Epigenet. 2020;12:136. doi: 10.1186/s13148-020-00929-y.
    1. Legoff L., D’Cruz S.C., Tevosian S., Primig M., Smagulova F. Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development. Cells. 2019;8:1559. doi: 10.3390/cells8121559.
    1. Skinner M.K., Nilsson E.E. Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology: Unified Evolution Theory. Environ. Epigenet. 2021;7:dvab012. doi: 10.1093/eep/dvab012.
    1. Bollati V., Baccarelli A. Environmental epigenetics. Heredity. 2010;105:105–112. doi: 10.1038/hdy.2010.2.
    1. Johns L.E., Kee F., Collins B.J., Patterson C.C., Houlston R.S. Colorectal cancer mortality in first-degree relatives of early-onset colorectal cancer cases. Dis. Colon. Rectum. 2002;45:681–686. doi: 10.1007/s10350-004-6267-0.
    1. Pearlman R., de la Chapelle A., Hampel H. Mutation Frequencies in Patients with Early-Onset Colorectal Cancer-Reply. JAMA Oncol. 2017;3:1587. doi: 10.1001/jamaoncol.2017.1744.
    1. Stanich P.P., Pelstring K.R., Hampel H., Pearlman R. A High Percentage of Early-age Onset Colorectal Cancer Is Potentially Preventable. Gastroenterology. 2021;160:1850–1852. doi: 10.1053/j.gastro.2020.12.009.
    1. Strum W.B., Boland C.R. Clinical and Genetic Characteristics of Colorectal Cancer in Persons under 50 Years of Age: A Review. Dig. Dis. Sci. 2019;64:3059–3065. doi: 10.1007/s10620-019-05644-0.
    1. Zhang Q., Berger F.G., Love B., Banister C.E., Murphy E.A., Hofseth L.J. Maternal stress and early-onset colorectal cancer. Med. Hypotheses. 2018;121:152–159. doi: 10.1016/j.mehy.2018.09.035.
    1. Zhang L., Shay J.W. Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer. J. Natl. Cancer Inst. 2017;109:djw332. doi: 10.1093/jnci/djw332.
    1. Hughes L.A., van den Brandt P.A., Goldbohm R.A., de Goeij A.F., de Bruïne A.P., van Engeland M., Weijenberg M.P. Childhood and adolescent energy restriction and subsequent colorectal cancer risk: Results from the Netherlands Cohort Study. Int. J. Epidemiol. 2010;39:1333–1344. doi: 10.1093/ije/dyq062.
    1. Keinan-Boker L., Vin-Raviv N., Liphshitz I., Linn S., Barchana M. Cancer incidence in Israeli Jewish survivors of World War II. J. Natl. Cancer Inst. 2009;101:1489–1500. doi: 10.1093/jnci/djp327.
    1. Murphy C.C., Singal A.G., Baron J.A., Sandler R.S. Decrease in Incidence of Young-Onset Colorectal Cancer Before Recent Increase. Gastroenterology. 2018;155:1716–1719. doi: 10.1053/j.gastro.2018.07.045.
    1. Siegel R.L., Fedewa S.A., Anderson W.F., Miller K.D., Ma J., Rosenberg P.S., Jemal A. Colorectal Cancer Incidence Patterns in the United States, 1974–2013. J. Natl. Cancer Inst. 2017;109:djw322. doi: 10.1093/jnci/djw322.
    1. Chang S.H., Patel N., Du M., Liang P.S. Trends in Early-onset vs Late-onset Colorectal Cancer Incidence by Race/Ethnicity in the United States Cancer Statistics Database. Clin. Gastroenterol. Hepatol. 2021:S1542-3565(21)00817-X. doi: 10.1016/j.cgh.2021.07.035.
    1. Murphy C.C., Wallace K., Sandler R.S., Baron J.A. Racial Disparities in Incidence of Young-Onset Colorectal Cancer and Patient Survival. Gastroenterology. 2019;156:958–965. doi: 10.1053/j.gastro.2018.11.060.
    1. Barreto S.G. Young-onset rectal cancer patients: In need of answers. Future Oncol. 2019;15:1053–1055. doi: 10.2217/fon-2019-0002.
    1. Boursi B., Haynes K., Mamtani R., Yang Y.X. Impact of antibiotic exposure on the risk of colorectal cancer. Pharm. Drug Saf. 2015;24:534–542. doi: 10.1002/pds.3765.
    1. Dik V.K., van Oijen M.G., Smeets H.M., Siersema P.D. Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case-Control Study. Dig. Dis. Sci. 2016;61:255–264. doi: 10.1007/s10620-015-3828-0.
    1. Pi Y., Gao K., Peng Y., Mu C.L., Zhu W.Y. Antibiotic-induced alterations of the gut microbiota and microbial fermentation in protein parallel the changes in host nitrogen metabolism of growing pigs. Animal. 2019;13:262–272. doi: 10.1017/S1751731118001416.
    1. Gerber J.S., Prasad P.A., Localio A.R., Fiks A.G., Grundmeier R.W., Bell L.M., Wasserman R.C., Rubin D.M., Keren R., Zaoutis T.E. Racial differences in antibiotic prescribing by primary care pediatricians. Pediatrics. 2013;131:677–684. doi: 10.1542/peds.2012-2500.
    1. Goyal M.K., Johnson T.J., Chamberlain J.M., Casper T.C., Simmons T., Alessandrini E.A., Bajaj L., Grundmeier R.W., Gerber J.S., Lorch S.A., et al. Racial and Ethnic Differences in Antibiotic Use for Viral Illness in Emergency Departments. Pediatrics. 2017;140:e20170203. doi: 10.1542/peds.2017-0203.
    1. Chen B., Du G., Guo J., Zhang Y. Bugs, drugs, and cancer: Can the microbiome be a potential therapeutic target for cancer management? Drug Discov. Today. 2019;24:1000–1009. doi: 10.1016/j.drudis.2019.02.009.
    1. Scott A.J., Alexander J.L., Merrifield C.A., Cunningham D., Jobin C., Brown R., Alverdy J., O’Keefe S.J., Gaskins H.R., Teare J., et al. International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut. 2019;68:1624–1632. doi: 10.1136/gutjnl-2019-318556.
    1. Tilg H., Adolph T.E., Gerner R.R., Moschen A.R. The Intestinal Microbiota in Colorectal Cancer. Cancer Cell. 2018;33:954–964. doi: 10.1016/j.ccell.2018.03.004.
    1. Wirbel J., Pyl P.T., Kartal E., Zych K., Kashani A., Milanese A., Fleck J.S., Voigt A.Y., Palleja A., Ponnudurai R., et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat. Med. 2019;25:679–689. doi: 10.1038/s41591-019-0406-6.
    1. Yachida S., Mizutani S., Shiroma H., Shiba S., Nakajima T., Sakamoto T., Watanabe H., Masuda K., Nishimoto Y., Kubo M., et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 2019;25:968–976. doi: 10.1038/s41591-019-0458-7.
    1. Yang T., Owen J.L., Lightfoot Y.L., Kladde M.P., Mohamadzadeh M. Microbiota impact on the epigenetic regulation of colorectal cancer. Trends Mol. Med. 2013;19:714–725. doi: 10.1016/j.molmed.2013.08.005.
    1. Brennan C.A., Garrett W.S. Fusobacterium nucleatum—Symbiont, opportunist and oncobacterium. Nat. Rev. Microbiol. 2019;17:156–166. doi: 10.1038/s41579-018-0129-6.
    1. Feng Q., Liang S., Jia H., Stadlmayr A., Tang L., Lan Z., Zhang D., Xia H., Xu X., Jie Z., et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat. Commun. 2015;6:6528. doi: 10.1038/ncomms7528.
    1. Flemer B., Lynch D.B., Brown J.M., Jeffery I.B., Ryan F.J., Claesson M.J., O’Riordain M., Shanahan F., O’Toole P.W. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut. 2017;66:633–643. doi: 10.1136/gutjnl-2015-309595.
    1. Kosumi K., Hamada T., Koh H., Borowsky J., Bullman S., Twombly T.S., Nevo D., Masugi Y., Liu L., da Silva A., et al. The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome. Am. J. Pathol. 2018;188:2839–2852. doi: 10.1016/j.ajpath.2018.08.015.
    1. Mima K., Cao Y., Chan A.T., Qian Z.R., Nowak J.A., Masugi Y., Shi Y., Song M., da Silva A., Gu M., et al. Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location. Clin. Transl. Gastroenterol. 2016;7:e200. doi: 10.1038/ctg.2016.53.
    1. Mima K., Nishihara R., Qian Z.R., Cao Y., Sukawa Y., Nowak J.A., Yang J., Dou R., Masugi Y., Song M., et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2016;65:1973–1980. doi: 10.1136/gutjnl-2015-310101.
    1. Mima K., Sukawa Y., Nishihara R., Qian Z.R., Yamauchi M., Inamura K., Kim S.A., Masuda A., Nowak J.A., Nosho K., et al. Fusobacterium nucleatum and T Cells in Colorectal Carcinoma. JAMA Oncol. 2015;1:653–661. doi: 10.1001/jamaoncol.2015.1377.
    1. Pleguezuelos-Manzano C., Puschhof J., Rosendahl Huber A., van Hoeck A., Wood H.M., Nomburg J., Gurjao C., Manders F., Dalmasso G., Stege P.B., et al. Mutational signature in colorectal cancer caused by genotoxic pks(+) E. coli. Nature. 2020;580:269–273. doi: 10.1038/s41586-020-2080-8.
    1. Hwang I., Park Y.J., Kim Y.R., Kim Y.N., Ka S., Lee H.Y., Seong J.K., Seok Y.J., Kim J.B. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB J. 2015;29:2397–2411. doi: 10.1096/fj.14-265983.
    1. O’Sullivan A., Farver M., Smilowitz J.T. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants. Nutr. Metab. Insights. 2015;8:1–9. doi: 10.4137/nmi.S29530.
    1. Ghosh T.S., Das M., Jeffery I.B., O’Toole P.W. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. eLife. 2020;9:e50240. doi: 10.7554/eLife.50240.
    1. Weinberg B.A., Wang H., Geng X., Shokralla S., Bakhshi E., Chaldekas K., Harris B.T., Clagett D., Marshall J. A comparison study of the intratumoral microbiome in younger verses older-onset colorectal cancer (COSMO CRC) J. Clin. Oncol. 2020;38:241. doi: 10.1200/JCO.2020.38.4_suppl.241.
    1. Cortes J., Cescon D.W., Rugo H.S., Nowecki Z., Im S.-A., Yusof M.M., Gallardo C., Lipatov O., Barrios C.H., Holgado E., et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J. Clin. Oncol. 2020;38:1000. doi: 10.1200/JCO.2020.38.15_suppl.1000.
    1. Ramasamy S., Singh S., Taniere P., Langman M.J., Eggo M.C. Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. Am. J. Physiol. Gastrointest. Liver Physiol. 2006;291:G288–G296. doi: 10.1152/ajpgi.00324.2005.
    1. Nguyen L.H., Ma W., Wang D.D., Cao Y., Mallick H., Gerbaba T.K., Lloyd-Price J., Abu-Ali G., Hall A.B., Sikavi D., et al. Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men. Gastroenterology. 2020;158:1313–1325. doi: 10.1053/j.gastro.2019.12.029.
    1. Nguyen L.H., Cao Y., Hur J., Mehta R.S., Sikavi D.R., Wang Y., Ma W., Wu K., Song M., Giovannucci E.L., et al. The Sulfur Microbial Diet Is Associated with Increased Risk of Early-Onset Colorectal Cancer Precursors. Gastroenterology. 2021;161:1423–1432. doi: 10.1053/j.gastro.2021.07.008.
    1. Hogan N.M., Hanley M., Hogan A.M., Sheehan M., McAnena O.J., Regan M.P., Kerin M.J., Joyce M.R. Awareness and uptake of family screening in patients diagnosed with colorectal cancer at a young age. Gastroenterol. Res. Pr. 2015;2015:194931. doi: 10.1155/2015/194931.
    1. Manne S., Markowitz A., Winawer S., Meropol N.J., Haller D., Rakowski W., Babb J., Jandorf L. Correlates of colorectal cancer screening compliance and stage of adoption among siblings of individuals with early onset colorectal cancer. Health Psychol. 2002;21:3–15. doi: 10.1037/0278-6133.21.1.3.
    1. Tsai M.H., Xirasagar S., Li Y.J., de Groen P.C. Colonoscopy screening among US adults aged 40 or older with a family history of colorectal cancer. Prev. Chronic. Dis. 2015;12:e80. doi: 10.5888/pcd12.140533.
    1. Boland C.R., Goel A., Patel S.G. The genetic and epigenetic landscape of early-onset colorectal cancer. Colorectal Cancer. 2020;9:CRC23. doi: 10.2217/crc-2020-0005.
    1. Zhunussova G., Afonin G., Abdikerim S., Jumanov A., Perfilyeva A., Kaidarova D., Djansugurova L. Mutation Spectrum of Cancer-Associated Genes in Patients with Early Onset of Colorectal Cancer. Front. Oncol. 2019;9:673. doi: 10.3389/fonc.2019.00673.
    1. Edwards A.W. GH Hardy (1908) and Hardy-Weinberg equilibrium. Genetics. 2008;179:1143–1150. doi: 10.1534/genetics.104.92940.
    1. Coletta A.M., Peterson S.K., Gatus L.A., Krause K.J., Schembre S.M., Gilchrist S.C., Pande M., Vilar E., You Y.N., Rodriguez-Bigas M.A., et al. Energy balance related lifestyle factors and risk of endometrial and colorectal cancer among individuals with lynch syndrome: A systematic review. Fam Cancer. 2019;18:399–420. doi: 10.1007/s10689-019-00135-7.
    1. Miguchi M., Hinoi T., Tanakaya K., Yamaguchi T., Furukawa Y., Yoshida T., Tamura K., Sugano K., Ishioka C., Matsubara N., et al. Alcohol consumption and early-onset risk of colorectal cancer in Japanese patients with Lynch syndrome: A cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum. Surg. Today. 2018;48:810–814. doi: 10.1007/s00595-018-1654-7.
    1. Van Duijnhoven F.J., Botma A., Winkels R., Nagengast F.M., Vasen H.F., Kampman E. Do lifestyle factors influence colorectal cancer risk in Lynch syndrome? Fam Cancer. 2013;12:285–293. doi: 10.1007/s10689-013-9645-8.
    1. Botma A., Vasen H.F., van Duijnhoven F.J., Kleibeuker J.H., Nagengast F.M., Kampman E. Dietary patterns and colorectal adenomas in Lynch syndrome: The GEOLynch cohort study. Cancer. 2013;119:512–521. doi: 10.1002/cncr.27726.
    1. Brouwer J.G., Makama M., van Woudenbergh G.J., Vasen H.F., Nagengast F.M., Kleibeuker J.H., Kampman E., van Duijnhoven F.J. Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome. Am. J. Clin. Nutr. 2017;106:1287–1294. doi: 10.3945/ajcn.117.152900.
    1. Eijkelboom A.H., Brouwer J.G.M., Vasen H.F.A., Bisseling T.M., Koornstra J.J., Kampman E., van Duijnhoven F.J.B. Diet quality and colorectal tumor risk in persons with Lynch syndrome. Cancer Epidemiol. 2020;69:101809. doi: 10.1016/j.canep.2020.101809.
    1. Dominguez-Valentin M., Sampson J.R., Seppälä T.T., Ten Broeke S.W., Plazzer J.P., Nakken S., Engel C., Aretz S., Jenkins M.A., Sunde L., et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the Prospective Lynch Syndrome Database. Genet. Med. 2020;22:15–25. doi: 10.1038/s41436-019-0596-9.
    1. Møller P., Seppälä T., Bernstein I., Holinski-Feder E., Sala P., Evans D.G., Lindblom A., Macrae F., Blanco I., Sijmons R., et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: First report from the prospective Lynch syndrome database. Gut. 2017;66:464–472. doi: 10.1136/gutjnl-2015-309675.
    1. Møller P., Seppälä T.T., Bernstein I., Holinski-Feder E., Sala P., Gareth Evans D., Lindblom A., Macrae F., Blanco I., Sijmons R.H., et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: A report from the Prospective Lynch Syndrome Database. Gut. 2018;67:1306–1316. doi: 10.1136/gutjnl-2017-314057.
    1. Chassaing B., Koren O., Goodrich J.K., Poole A.C., Srinivasan S., Ley R.E., Gewirtz A.T. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519:92–96. doi: 10.1038/nature14232.
    1. Roberts C.L., Keita A.V., Duncan S.H., O’Kennedy N., Söderholm J.D., Rhodes J.M., Campbell B.J. Translocation of Crohn’s disease Escherichia coli across M-cells: Contrasting effects of soluble plant fibres and emulsifiers. Gut. 2010;59:1331–1339. doi: 10.1136/gut.2009.195370.
    1. Roberts C.L., Rushworth S.L., Richman E., Rhodes J.M. Hypothesis: Increased consumption of emulsifiers as an explanation for the rising incidence of Crohn’s disease. J. Crohn’s Colitis. 2013;7:338–341. doi: 10.1016/j.crohns.2013.01.004.
    1. Swidsinski A., Ung V., Sydora B.C., Loening-Baucke V., Doerffel Y., Verstraelen H., Fedorak R.N. Bacterial overgrowth and inflammation of small intestine after carboxymethylcellulose ingestion in genetically susceptible mice. Inflamm. Bowel. Dis. 2009;15:359–364. doi: 10.1002/ibd.20763.
    1. Viennois E., Chassaing B. First victim, later aggressor: How the intestinal microbiota drives the pro-inflammatory effects of dietary emulsifiers? Gut Microbes. 2018;9:1–4. doi: 10.1080/19490976.2017.1421885.
    1. Viennois E., Merlin D., Gewirtz A.T., Chassaing B. Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis. Cancer Res. 2017;77:27–40. doi: 10.1158/0008-5472.CAN-16-1359.
    1. Viennois E., Chassaing B. Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma. Int. J. Mol. Sci. 2021;22:2602. doi: 10.3390/ijms22052602.
    1. Cougnoux A., Dalmasso G., Martinez R., Buc E., Delmas J., Gibold L., Sauvanet P., Darcha C., Dechelotte P., Bonnet M., et al. Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut. 2014;63:1932–1942. doi: 10.1136/gutjnl-2013-305257.
    1. Sears C.L., Garrett W.S. Microbes, microbiota, and colon cancer. Cell Host Microbe. 2014;15:317–328. doi: 10.1016/j.chom.2014.02.007.
    1. Dziubanska-Kusibab P.J., Berger H., Battistini F., Bouwman B.A.M., Iftekhar A., Katainen R., Cajuso T., Crosetto N., Orozco M., Aaltonen L.A., et al. Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat. Med. 2020;26:1063–1069. doi: 10.1038/s41591-020-0908-2.
    1. Payros D., Secher T., Boury M., Brehin C., Menard S., Salvador-Cartier C., Cuevas-Ramos G., Watrin C., Marcq I., Nougayrede J.P., et al. Maternally acquired genotoxic Escherichia coli alters offspring’s intestinal homeostasis. Gut Microbes. 2014;5:313–325. doi: 10.4161/gmic.28932.
    1. Ferrarese R., Zuppardo R.A., Puzzono M., Mannucci A., Amato V., Ditonno I., Patricelli M.G., Raucci A.R., Clementi M., Elmore U., et al. Oral and Fecal Microbiota in Lynch Syndrome. J. Clin. Med. 2020;9:2735. doi: 10.3390/jcm9092735.
    1. Yan Y., Drew D.A., Markowitz A., Lloyd-Price J., Abu-Ali G., Nguyen L.H., Tran C., Chung D.C., Gilpin K.K., Meixell D., et al. Structure of the Mucosal and Stool Microbiome in Lynch Syndrome. Cell Host Microbe. 2020;27:585–600. doi: 10.1016/j.chom.2020.03.005.

Source: PubMed

3
Subskrybuj