Risk Factors of Small Intestine Cancer: An Epidemiological Analysis and Their Role in Early Diagnosis - A Literature Review
DOI:
https://doi.org/10.12775/QS.2025.37.57159Keywords
small intestine, risk factors, epidemiology, ileum cancerAbstract
Introduction: Small intestinal cancer is a rare form of cancer affecting the duodenum, jejunum, or ileum. Its incidence is increasing, although it is less commonly diagnosed than colorectal cancers. Understanding risk factors is crucial for early detection and prevention. These factors include non-modifiable ones like sex, race, age, and genetic conditions, as well as modifiable factors like diet, alcohol, smoking, and obesity.
Materials and Methods: A search of PubMed with the keywords "small intestine cancer" and "risk factors" identified 928 articles. After review, 48 publications and one textbook, were included.
Results: Small intestine cancer is more common in men and African Americans. Genetic conditions such as Lynch syndrome, Familial Adenomatous Polyposis (FAP), Peutz-Jeghers syndrome (PJS), and Multiple Endocrine Neoplasia (MEN1) significantly increase the risk. Chronic conditions like Crohn’s disease and celiac disease also increase risk. Diets high in red meats, processed foods, and animal fats, are linked to higher risk.
Discussion: Age and sex are key non-modifiable risk factors, with risk increasing with age, particularly over 60. Genetic conditions like Lynch syndrome, FAP, and PJS are major contributors. Chronic inflammatory diseases such as Crohn’s and celiac disease raise risk. Diets rich in animal fats, processed meats, and smoking contribute to higher risks, as does obesity. Healthy diet, quitting smoking, and maintaining a healthy weight, may reduce risk.
Conclusion: Genetic mutations, such as those in Lynch syndrome, FAP, and PJS, are significant risk factors, while lifestyle factors like diet, smoking, and obesity also play a role. Increased surveillance for individuals with genetic predispositions or inflammatory conditions may allow for earlier detection. Despite limited data, a balanced diet, weight management, and avoiding smoking may help reduce risk. Further research is needed to improve prevention strategies.
References
1. Barsouk A, Rawla P, Barsouk A, Thandra KC. Epidemiology of Cancers of the Small Intestine: Trends, Risk Factors, and Prevention. Med Sci (Basel). 2019;7(3):46. Published 2019 Mar 17. doi:10.3390/medsci7030046
2. Aparicio T, Pachev A, Laurent-Puig P, Svrcek M. Epidemiology, Risk Factors and Diagnosis of Small Bowel Adenocarcinoma. Cancers (Basel). 2022;14(9):2268. Published 2022 May 2. doi:10.3390/cancers14092268
3. Cross AJ, Hollenbeck AR, Park Y. A large prospective study of risk factors for adenocarcinomas and malignant carcinoid tumors of the small intestine. Cancer Causes Control. 2013;24(9):1737-1746. doi:10.1007/s10552-013-0251-8
4. Dąbrowski AD, ed. Wielka Interna Gastroenterologia. Vol 2. 2nd ed. Medical Tribune Polska; 2019.
5. Jagelman DG, DeCosse JJ, Bussey HJ. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet. 1988;1(8595):1149-1151. doi:10.1016/s0140-6736(88)91962-9
6. Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology. 1992;102(6):1980-1982. doi:10.1016/0016-5085(92)90322-p
7. Aparicio T, Henriques J, Manfredi S, et al. Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients. Int J Cancer. 2020;147(4):967-977. doi:10.1002/ijc.32860
8. Bonadona V, Bonaïti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304-2310. doi:10.1001/jama.2011.743
9. Møller P, Seppälä TT, Bernstein I, 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 [published correction appears in Gut. 2020 Jun;69(6):e4. doi: 10.1136/gutjnl-2017-314057corr1]. Gut. 2018;67(7):1306-1316. doi:10.1136/gutjnl-2017-314057
10. Koornstra JJ, Kleibeuker JH, Vasen HF. Small-bowel cancer in Lynch syndrome: is it time for surveillance?. Lancet Oncol. 2008;9(9):901-905. doi:10.1016/S1470-2045(08)70232-8
11. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119(6):1447-1453. doi:10.1053/gast.2000.20228
12. Lodish MB, Stratakis CA. Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes. Best Pract Res Clin Endocrinol Metab. 2010;24(3):439-449. doi:10.1016/j.beem.2010.02.002
13. Palascak-Juif V, Bouvier AM, Cosnes J, et al. Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma de novo. Inflamm Bowel Dis. 2005;11(9):828-832. doi:10.1097/01.mib.0000179211.03650.b6
14. Ullman TA. Cancer in Inflammatory Bowel Disease. Curr Treat Options Gastroenterol. 2002;5(3):163-171. doi:10.1007/s11938-002-0038-6
15. Swinson CM, Slavin G, Coles EC, Booth CC. Coeliac disease and malignancy. Lancet. 1983;1(8316):111-115. doi:10.1016/s0140-6736(83)91754-3
16. Askling J, Linet M, Gridley G, Halstensen TS, Ekström K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology. 2002;123(5):1428-1435. doi:10.1053/gast.2002.36585
17. Peters U, Askling J, Gridley G, Ekbom A, Linet M. Causes of death in patients with celiac disease in a population-based Swedish cohort. Arch Intern Med. 2003;163(13):1566-1572. doi:10.1001/archinte.163.13.1566
18. Emilsson L, Semrad C, Lebwohl B, Green PHR, Ludvigsson JF. Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease. Gastroenterology. 2020;159(5):1686-1694.e2. doi:10.1053/j.gastro.2020.07.007
19. Fujimori S, Hamakubo R, Hoshimoto A, et al. Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine. World J Gastroenterol. 2022;28(39):5658-5665. doi:10.3748/wjg.v28.i39.5658
20. Chow WH, Linet MS, McLaughlin JK, Hsing AW, Chien HT, Blot WJ. Risk factors for small intestine cancer. Cancer Causes Control. 1993;4(2):163-169. doi:10.1007/BF00053158
21. Wu AH, Yu MC, Mack TM. Smoking, alcohol use, dietary factors and risk of small intestinal adenocarcinoma. Int J Cancer. 1997;70(5):512-517. doi:10.1002/(sici)1097-0215(19970304)70:5<512::aid-ijc4>3.0.co;2-0
22. Cross AJ, Leitzmann MF, Subar AF, Thompson FE, Hollenbeck AR, Schatzkin A. A prospective study of meat and fat intake in relation to small intestinal cancer. Cancer Res. 2008;68(22):9274-9279. doi:10.1158/0008-5472.CAN-08-2015
23. Schatzkin A, Park Y, Leitzmann MF, Hollenbeck AR, Cross AJ. Prospective study of dietary fiber, whole grain foods, and small intestinal cancer. Gastroenterology. 2008;135(4):1163-1167. doi:10.1053/j.gastro.2008.07.015
24. Negri E, Bosetti C, La Vecchia C, Fioretti F, Conti E, Franceschi S. Risk factors for adenocarcinoma of the small intestine. Int J Cancer. 1999;82(2):171-174. doi:10.1002/(sici)1097-0215(19990719)82:2<171::aid-ijc3>3.0.co;2-t
25. Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Risk factors associated with neuroendocrine tumors: A U.S.-based case-control study. Int J Cancer. 2008;123(4):867-873. doi:10.1002/ijc.23529
26. Kaerlev L, Teglbjaerg PS, Sabroe S, et al. Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case-control study. Cancer Causes Control. 2000;11(9):791-797. doi:10.1023/a:1008920502888
27. Curtin K, Cannon-Albright LA, VanDerslice J, et al. Associations of Tobacco and Alcohol Use with Risk of Neuroendocrine Tumors of the Small Intestine in Utah. Cancer Epidemiol Biomarkers Prev. 2019;28(12):1998-2004. doi:10.1158/1055-9965.EPI-19-0465
28. Kaerlev L, Teglbjaerg PS, Sabroe S, et al. The importance of smoking and medical history for development of small bowel carcinoid tumor: a European population-based case-control study. Cancer Causes Control. 2002;13(1):27-34. doi:10.1023/a:1013922226614
29. Boffetta P, Hazelton WD, Chen Y, et al. Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium. Ann Oncol. 2012;23(7):1894-1898. doi:10.1093/annonc/mdr562
30. Kaerlev L, Teglbjaerg PS, Sabroe S, et al. Occupational risk factors for small bowel carcinoid tumor: a European population-based case-control study. J Occup Environ Med. 2002;44(6):516-522. doi:10.1097/00043764-200206000-00012
31. Chen CC, Neugut AI, Rotterdam H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Cancer Epidemiol Biomarkers Prev. 1994;3(3):205-207.
32. Wolk A, Gridley G, Svensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001;12(1):13-21. doi:10.1023/a:1008995217664 [34] Samanic C., Chow W.H., Gridley G., Jarvholm B., Fraumeni J.F., Jr. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 2006;17:901–909. doi: 10.1007/s10552-006-0023-9.
33. Bjørge T, Tretli S, Engeland A. Height and body mass index in relation to cancer of the small intestine in two million Norwegian men and women. Br J Cancer. 2005;93(7):807-810. doi:10.1038/sj.bjc.6602789
34. Pang Y, Kartsonaki C, Guo Y, et al. Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people. Br J Cancer. 2018;119(2):248-250. doi:10.1038/s41416-018-0124-8
35. Lu Y, Cross AJ, Murphy N, et al. Comparison of abdominal adiposity and overall obesity in relation to risk of small intestinal cancer in a European Prospective Cohort. Cancer Causes Control. 2016;27(7):919-927. doi:10.1007/s10552-016-0772-z
36. Bansal P, Sonnenberg A. Comorbid occurrence of cholelithiasis and gastrointestinal cancer. Eur J Gastroenterol Hepatol. 1996;8(10):985-988. doi:10.1097/00042737-199610000-00009
37. Nogueira L, Freedman ND, Engels EA, Warren JL, Castro F, Koshiol J. Gallstones, cholecystectomy, and risk of digestive system cancers. Am J Epidemiol. 2014;179(6):731-739. doi:10.1093/aje/kwt322
38. Teng F, Tang Y, Lu Z, Chen K, Chen Z. Investigating causal links between gallstones, cholecystectomy, and 33 site-specific cancers: a Mendelian randomization post-meta-analysis study. BMC Cancer. 2024;24(1):1192. Published 2024 Sep 27. doi:10.1186/s12885-024-12906-2
39. Søgaard KK, Erichsen R, Lund JL, Farkas DK, Sørensen HT. Cholangitis and subsequent gastrointestinal cancer risk: a Danish population-based cohort study. Gut. 2014;63(2):356-361. doi:10.1136/gutjnl-2013-305039
40. Nagel G, Bjørge T, Jaensch A, et al. Metabolic factors and the risk of small intestine cancers: Pooled study of 800 000 individuals in the metabolic syndrome and cancer project. Int J Cancer. 2021;149(1):66-74. doi:10.1002/ijc.33530
41. Cluze C, Delafosse P, Seigneurin A, Colonna M. Incidence of second cancer within 5 years of diagnosis of a breast, prostate or colorectal cancer: a population-based study. Eur J Cancer Prev. 2009;18(5):343-348. doi:10.1097/CEJ.0b013e32832abd76
42. Neugut AI, Santos J. The association between cancers of the small and large bowel. Cancer Epidemiol Biomarkers Prev. 1993;2(6):551-553.
43. Leoncini E, Carioli G, La Vecchia C, Boccia S, Rindi G. Risk factors for neuroendocrine neoplasms: a systematic review and meta-analysis. Ann Oncol. 2016;27(1):68-81. doi:10.1093/annonc/mdv505
44. Hiripi E, Lorenzo Bermejo J, Li X, Sundquist J, Hemminki K. Familial association of pancreatic cancer with other malignancies in Swedish families. Br J Cancer. 2009;101(10):1792-1797. doi:10.1038/sj.bjc.6605363
45. Skriver C, Maltesen T, Dehlendorff C, et al. Long-term aspirin use and cancer risk: a 20-year cohort study. J Natl Cancer Inst. 2024;116(4):530-538. doi:10.1093/jnci/djad231
46. Vestergaard P. Occurrence of gastrointestinal cancer in users of bisphosphonates and other antiresorptive drugs against osteoporosis. Calcif Tissue Int. 2011;89(6):434-441. doi:10.1007/s00223-011-9539-4
47. Larsson SC, Mason AM, Vithayathil M, et al. Circulating vitamin C and digestive system cancers: Mendelian randomization study. Clin Nutr. 2022;41(9):2031-2035. doi:10.1016/j.clnu.2022.07.040
48. Meijers JM, Swaen GM, Slangen JJ, van Vliet K, Sturmans F. Long-term mortality in miners with coal workers' pneumoconiosis in The Netherlands: a pilot study. Am J Ind Med. 1991;19(1):43-50. doi:10.1002/ajim.4700190106
49. Liu Q, Adami HO, Reichenberg A, Kolevzon A, Fang F, Sandin S. Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study. PLoS Med. 2021;18(10):e1003840. Published 2021 Oct 21. doi:10.1371/journal.pmed.1003840
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Copyright (c) 2025 Paweł Miklis, Michał Pniak, Maciej Mawlichanów , Adrian Różycki , Marta Wojtczak , Krzysztof Szerej , Aleksandra Ciesielska , Natalia Myśliwiec , Aleksandra Sieradzka , Alicja Kot
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