Review of Controllable Risk Factors for the Development of Malignant Neoplasms of the Digestive Organs

Relevance. It is known that malignant neoplasms develop over a long period, under the constant influence of risk factors. Among them some biological agents, smoking and alcohol consumption are known to science. At the present stage the possibility of influence of such risk factors as sleep disorders, eating habits, obesity and overweight is being studied.
Aim. To estimate, according to the literature data, the degree of influence of some controllable risk factors on the development of malignant neoplasms of the digestive organs.
Materials and methods. The results of 130 articles conducted by Russian and foreign researchers were studied, from which 31 studies were selected that met the requirements of the selection criteria and corresponded to the objectives of the study. Based on the data presented in the studies, we analyzed relative risks, odds ratios and risk ratios of some controllable risk factors for the development of malignant neoplasms of the digestive organs.
Results and Discussion. H. pylori, which contributes to the development of gastric cancer (OR 2.39 [95% CI 1.53–3.74]), stands out among the best-known cancer risk factors. Alcohol, a group 1 carcinogen (WHO), increases the risk (OR) of esophageal cancer by a factor of 2 [95% CI 1.66–2.40], liver cancer by a factor of 1.83 [95% CI 1.39–2.40] and gastric cancer by a factor of 1.54 [95% CI 1.10–2.15]. Smoking has been shown to cause more gastric cardia cancer (Hazard ratio/КШ 4.10 [95% CI: 1.76–9.57]) than distal gastric cancer (КШ 1.94 [95% CI: 1.05–3.60]). Most of the trials also focused on the effect of dietary habits on the development of cancer. For example, consumption of 100 g/day of red and processed meat was associated with the development of colorectal cancer (OR – 1.25, [95% CI: 1.10–1.43] and OR – 1.31, [95% CI: 1.13–1.52], respectively). Meanwhile, the researchers found an association between increased BMI and the risk of esophageal adenocarcinoma (OR, 1.10 [95% CI 1.04–1.17]). Sweet tea and fresh food consumption have also been shown to play a protective role against the development of gastrointestinal cancer (OR 0.26 [95% CI 0.14–0.47] and OR 0.57 [95% CI 0.37–0.88], respectively). In addition, the literature suggests a positive effect of sleep disorders and depression on the development of cancer.
Conclusions. The presence of lifestyle risk factors such as the presence of H.pylori, consumption of fried and stale foods, daily consumption of red and processed meat of 100g or more has a significant impact on the development of digestive organ cancer. In addition, known WHO eradicable factors such as tobacco smoking and alcohol consumption have evidence of their influence on the development of digestive cancers. However, these risk factors require further in-depth study to develop systematic prevention measures. However, all the risk factors studied are manageable. If their influence is reduced or eliminated from human activity, the risk of developing digestive organ cancer is significantly reduced.

1. International Agency for Research on Cancer (IARC), World Health Organization (WHO). The global burden of cancer is growing in parallel with the need for services [Internet]. 2024 (In Russ.). Available at: https://www.who.int/ru/news/item/01-02-2024-global-cancer-burden-growing- amidst-mounting-need-for-services

2. World Health Organization (WHO). Obesity and overweight [Internet]. 2024. Available at: https://www.who.int/ru/news-room/fact-sheets/detail/obesity-and-overweight

3. World Cancer Research/American Institute of Cancer Research. Diet, Nutrition, Physical Activity and Cancer: A Global Perspective. Continious Update Project Expert Report 2018. [Internet]. Available at: dietandcancerreport.org

4. Polednak AP. Estimating the number of U.S. incident cancers attributable to obesity and the impact on temporal trends in incidence rates for obesity-related cancers. Cancer Detect Prev. Jan 2008;32(3):190–9. DOI: 10.1016/j.cdp.2008.08.004

5. Il’nitskiy A.P. Pervichnaya profilaktika raka - M.: ABV-press, 2023;412 (In Russ.). ISBN 978-5-6048884-2-1.

6. Zhernakova YuV, Zheleznova EA, Chazova IE, и др. The prevalence of abdominal obesity and the association with socioeconomic status in Regions of the Russian Federation, the results of the epidemiological study – ESSE-RF. Ter Arkh. 2018; Vol.90 N10: P14–22. DOI: 10.26442/terarkh2018901014-22

7. Ford ES, Mokdad AH, Giles WH. Trends in Waist Circumference among U.S. Adults. Obes Res. Oct 2003;11(10):1223–31.

8. Pearson-Stuttard J, Zhou B, Kontis V, et al. Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment. Lancet Diabetes Endocrinol. June 2018;6(6):e6–15. DOI: 10.1016/S2213-8587(18)30150-5

9. Corley DA, Kubo A, Zhao W. Abdominal Obesity and the Risk of Esophageal and Gastric Cardia Carcinomas. Cancer Epidemiol Biomarkers Prev. 1 Feb 2008;17(2):352–8. DOI: 10.1158/1055-9965.EPI-07-0748

10. Lin CL, Liu TC, Wang YN, et al. The Association Between Sleep Disorders and the Risk of Colorectal Cancer in Patients: A Population-based Nested Case–Control Study. In Vivo. 2019;33(2):573–9. DOI: 10.21873/invivo.11513

11. Loosen S, Krieg S, Krieg A, et al. Are sleep disorders associated with the risk of gastrointestinal cancer ? A case–control study. J Cancer Res Clin Oncol. Oct 2023;149(13):11369– 78. DOI: 10.1007/s00432-023-05009-1

12. Thompson CL, Larkin EK, Patel S, et al. Short duration of sleep increases risk of colorectal adenoma. Cancer. 15 Feb 2011;117(4):841–7. DOI: 10.1002/cncr.25507

13. Secretan B, Straif K, Baan R, et al. A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. Nov 2009;10(11):1033–4. DOI: 10.1016/S1470-2045(09)70326-2

14. Trédaniel J, Boffetta P, Buiatti E, et al. Tobacco smoking and gastric cancer: Review and meta-analysis. Int J Cancer. 7 Aug 1997;72(4):565–73. DOI: 10.1002/(SICI)1097-0215(19970807)72:4<565::AID-IJC3>3.0.CO;2-O

15. Wu M, Zhao JK, Zhang ZF, et al. Smoking and alcohol drinking increased the risk of esophageal cancer among Chinese men but not women in a high-risk population. Cancer Causes Control. April 2011;22(4):649–57. DOI: 10.1007/s10552-011-9737-4

16. Sun X, Chen W, Chen Z, et al. Population-based case-control study on risk factors for esophageal cancer in five high-risk areas in China. Asian Pac J Cancer Prev. 2010;11(6):1631–6. PMID: 21338208.

17. Ladeiras-Lopes R, Pereira AK, Nogueira A, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. Sep 2008;19(7):689–701. DOI: 10.1007/s10552-008-9132-y

18. González CA, Pera G, Agudo A, et al. Smoking and the risk of gastric cancer in the European Prospective Investigation In to Cancer and Nutrition (EPIC). Int J Cancer. 20 Nov 2003;107(4):629–34. DOI: 10.1002/ijc.11426

19. Freedman ND, Abnet CC, Leitzmann MF, et al. A Prospective Study of Tobacco, Alcohol, and the Risk of Esophageal and Gastric Cancer Subtypes. Am J Epidemiol. 10 March 2007;165(12):1424–33. DOI: 10.1093/aje/kwm051

20. Oze I, Matsuo K, Ito H, et al. Cigarette Smoking and Esophageal Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiologic Evidence Among the Japanese Population. Jpn J Clin Oncol. 1 Jan 2012;42(1):63–73. DOI: 10.1093/jjco/hyr170

21. Nishino Y, Inoue M, Tsuji I, et al. Tobacco Smoking and Gastric Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiologic Evidence among the Japanese Population. Jpn J Clin Oncol. 1 Dec 2006;36(12):800–7. DOI: 10.1093/jjco/hyl112

22. Nikolenko VN, Kochurova YEV, Mukhanov AA. Etiologicheskiye faktory vozniknoveniya ploskokletochnogo raka slizistoy obolochki organov polosti rta. Voprosy onkologii. 2017;63(5):702–6 (In Russ.).

23. Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2007;89:1–592.

24. Gupta S, Gupta R, Sinha D, et al. Relationship between type of smokeless tobacco & risk of cancer: A systematic review. Indian J Med Res. 2018;148(1):56. DOI: 10.4103/ijmr.IJMR_2023_17

25. He F, Sha Y, Wang B. Relationship between alcohol consumption and the risks of liver cancer, esophageal cancer, and gastric cancer in China: Meta-analysis based on case–control studies. Medicine (Baltimore). 20 Aug 2021;100(33):e26982. DOI: 10.1097/MD.0000000000026982

26. Yang X, Chen X, Zhuang M, et al. Smoking and alcohol drinking in relation to the risk of esophageal squamous cell carcinoma: A population-based case-control study in China. Sci Rep. 8 Dec 2017;7(1):17249. DOI: 10.3389/fcimb.2024.1353094

27. Im PK, Millwood IY, Kartsonaki C, et al. Alcohol drinking and risks of total and site‐specific cancers in China: A 10‐year prospective study of 0.5 million adults. Int J Cancer. Aug 2021;149(3):522–34. DOI: 10.1002/ijc.33538

28. Kahrizsangi MA, Ebrahimi Z, Shateri Z, et al. Carbohydrate quality indices and colorectal cancer risk: a case-control study. BMC Cancer. 17 April 2023;23(1):347. DOI: 10.1186/s12885-023-10786-6

29. Giovannucci E. Physical Activity, Obesity, and Risk for Colon Cancer and Adenoma in Men. Ann Intern Med. 1 March 1995;122(5):327. DOI: 10.7326/0003-4819-122-5-199503010-00002

30. Moghaddam AA, Woodward M, Huxley R. Obesity and Risk of Colorectal Cancer: A Meta-analysis of 31 Studies with 70,000 Events. Cancer Epidemiol Biomarkers Prev. 1 Dec 2007;16(12):2533–47. DOI: 10.1158/1055-9965.EPI-07-0708

31. Chan DSM, Lau R, Aune D, et al. Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies. Tomé D, editor. PLoS ONE. 6 June 2011;6(6):e20456. DOI: 10.1371/journal.pone.0020456

32. Cross AJ, Sinha R. Meat‐related mutagens/carcinogens in the etiology of colorectal cancer. Environ Mol Mutagen. Jan 2004;44(1):44–55. DOI: 10.1002/em.20030

33. Bingham SA. High-meat diets and cancer risk. Proc Nutr Soc. May 1999;58(2):243–8. DOI: 10.1017/S0029665199000336

34. Norat T, Riboli E. Meat Consumption and Colorectal Cancer: A Review of Epidemiologic Evidence. Nutr Rev. 27 April 2009;59(2):37–47. DOI: 10.1111/j.1753-4887.2001.tb06974.x

35. Sinha R, Rothman N, Brown ED, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res. 1 Dec 1994;54(23):6154–9.

36. Zhang T, Song SS, Liu M, Park S. Association of Fried Food Intake with Gastric Cancer Risk: A Systemic Review and Meta-Analysis of Case–Control Studies. Nutrients. 30 June 2023 г.;15(13):2982. DOI: 10.3390/nu15132982

37. R Sinha, W H Chow, M Kulldorff. Well-done, grilled red meat increases the risk of colorectal adenomas [Internet]. 1999. Available at: https://pubmed.ncbi.nlm.nih.gov/10485479/

38. Nadeem S, Dinesh K, Tasneef Z, et al. Dietary risk factors in gastrointestinal cancers: A case–control study in North India. J Cancer Res Ther. 2023.;19(5):1385–91. DOI: 10.4103/jcrt.jcrt_1830_21

39. Tsukamoto T, Nakagawa M, Kiriyama Y, et al. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond. Int J Mol Sci. 3 Aug 2017;18(8):1699. DOI: 10.3390/ijms18081699

40. Hu PJ, Li YY, Zhou MH, et al. Helicobacter pylori associated with a high prevalence of duodenal ulcer disease and a low prevalence of gastric cancer in a developing nation. Gut. 1 Feb 1995;36(2):198–202. DOI: 10.1136/gut.36.2.198

41. Asaka M, Kato M, Kudo M, et al. Atrophic Changes of Gastric Mucosa Are Caused by Helicobacter pylori Infection Rather Than Aging: Studies in Asymptomatic Japanese Adults. Helicobacter. March 1996;1(1):52–6. DOI: 10.1111/j.1523-5378.1996.tb00008.x

42. Graham DY. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J Gastroenterol. 2014;20(18):5191. DOI: 10.3748/wjg.v20.i18.5191

43. Nagy P, Johansson S, Molloy-Bland M. Systematic review of time trends in the prevalence of Helicobacter pylori infection in China and the USA. Gut Pathog. Dec 2016;8(1):8. DOI: 10.1186/s13099-016-0091-7

44. Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 1 June 2007;56(6):772–81. DOI: 10.1136/gut.2006.101634

45. Wang C, Yuan Y, Hunt RH. The Association Between Helicobacter pylori Infection and Early Gastric Cancer: A Meta-Analysis. Am J Gastroenterol. Aug 2007;102(8):1789–98. DOI: 10.1111/j.1572-0241.2007.01335.x

46. Yokota S, Konno M, Fujiwara S, et al. Intrafamilial, Preferentially Mother‐to‐Child and Intraspousal, Helicobacter pylori Infection in Japan Determined by Mutilocus Sequence Typing and Random Amplified Polymorphic DNA Fingerprinting. Helicobacter. Oct 2015;20(5):334–42. DOI: 10.1111/hel.12217

47. Youn Nam S, Park BJ, Nam JH, et al. Association of current Helicobacter pylori infection and metabolic factors with gastric cancer in 35,519 subjects: A cross‐sectional study. United Eur Gastroenterol J. March 2019;7(2):287–96. DOI: 10.1177/2050640618819402

48. Miftahussurur M, Waskito LA, Fauzia KA, et al. Overview of Helicobacter pylori Infection in Indonesia: What Distinguishes It from Countries with High Gastric Cancer Incidence? Gut Liver. 15 Sep 2021; 15(5):653–65. DOI: 10.5009/gnl20019

49. Yang S, Hao S, Ye H, et al. Cross-talk between Helicobacter pylori and gastric cancer: a scientometric analysis. Front Cell Infect Microbiol. 31 Jan 2024; 14 1353094. DOI: 10.3389/fcimb.2024.1353094

50. Smith MF, Mitchell A, Li G, et al. Toll-like Receptor (TLR) 2 and TLR5, but Not TLR4, Are Required for Helicobacter pylori-induced NF-κB Activation and Chemokine Expression by Epithelial Cells. J Biol Chem. Aug 2003;: 278(35): 32552–60. DOI: 10.1074/jbc.M305536200