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Evaluation of the risk factors associated with rectal neuroendocrine tumors: a big data analytic study from a health screening center

  • Original Article—Alimentary Tract
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Abstract

Background

Rectal neuroendocrine tumor (NET) is the most common NET in Asia. The risk factors associated with rectal NETs are unclear because of the overall low incidence rate of these tumors and the associated difficulty in conducting large epidemiological studies on rare cases. The aim of this study was to exploit the benefits of big data analytics to assess the risk factors associated with rectal NET.

Methods

A retrospective case–control study was conducted, including 102 patients with histologically confirmed rectal NETs and 52,583 healthy controls who underwent screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea between January 2002 and December 2012. Information on different risk factors was collected and logistic regression analysis applied to identify predictive factors.

Results

Four factors were significantly associated with rectal NET: higher levels of cholesterol [odds ratio (OR) = 1.007, 95 % confidence interval (CI), 1.001–1.013, p = 0.016] and ferritin (OR = 1.502, 95 % CI, 1.167–1.935, p = 0.002), presence of metabolic syndrome (OR = 1.768, 95 % CI, 1.071–2.918, p = 0.026), and family history of cancer among first-degree relatives (OR = 1.664, 95 % CI, 1.019–2.718, p = 0.042).

Conclusion

The findings of our study demonstrate the benefits of using big data analytics for research and clinical risk factor studies. Specifically, in this study, this analytical method was applied to identify higher levels of serum cholesterol and ferritin, metabolic syndrome, and family history of cancer as factors that may explain the increasing incidence and prevalence of rectal NET.

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References

  1. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–68.

    Article  CAS  PubMed  Google Scholar 

  2. Karzinoide SO. Tumoren des Dunndarms. Frankf Z Pathol. 1907;1:426–32.

    Google Scholar 

  3. Jernman J, Valimaki MJ, Louhimo J, Haglund C, Arola J. The novel WHO 2010 classification for gastrointestinal neuroendocrine tumours correlates well with the metastatic potential of rectal neuroendocrine tumours. Neuroendocrinology. 2012;95:317–24.

    Article  CAS  PubMed  Google Scholar 

  4. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Geneva: World Health Organization, 2010.

  5. Godwin JD. 2nd. Carcinoid tumors. An analysis of 2,837 cases. Cancer. 1975;36:560–9.

    Article  PubMed  Google Scholar 

  6. Naunheim KS, Zeitels J, Kaplan EL, et al. Rectal carcinoid tumors—treatment and prognosis. Surgery. 1983;94:670–6.

  7. Scherubl H. Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy. 2009;41:162–5.

    Article  CAS  PubMed  Google Scholar 

  8. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  CAS  PubMed  Google Scholar 

  9. Cho MY, Kim JM, Sohn JH, et al. Current trends of the incidence and pathological diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Korea 2000–2009: multicenter study. Cancer Res Treat. 2012;44:157–65.

  10. Ito T, Sasano H, Tanaka M, et al. Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol. 2010;45:234–43.

    Article  PubMed  Google Scholar 

  11. Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer. 2008;113:2655–64.

    Article  PubMed  Google Scholar 

  12. Konishi T, Watanabe T, Muto T, Kotake K, Nagawa H. Site distribution of gastrointestinal carcinoids differs between races. Gut. 2006;55:1051–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mandair D, Caplin ME. Colonic and rectal NET’s. Best Pract Res Clin Gastroenterol. 2012;26:775–89.

    Article  PubMed  Google Scholar 

  14. Fan J, Han F, Liu H. Challenges of big data analysis. Natl Sci Rev. 2014;1:293–314.

  15. Chen CC, Neugut AI, Rotterdam H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Cancer Epidemiol Biomarkers Prev. 1994;3:205–7.

    CAS  PubMed  Google Scholar 

  16. Chow WH, Linet MS, McLaughlin JK, Hsing AW, Chien HT, Blot WJ. Risk factors for small intestine cancer. Cancer Causes Control. 1993;4:163–9.

    Article  CAS  PubMed  Google Scholar 

  17. 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;68:9274–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Feldman JM, Plonk JW, Bivens CH, Lebovitz HE. Glucose intolerance in the carcinoid syndrome. Diabetes. 1975;24:664–71.

    Article  CAS  PubMed  Google Scholar 

  19. 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;123:867–73.

    Article  CAS  PubMed  Google Scholar 

  20. Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Family history of cancer and associated risk of developing neuroendocrine tumors: a case-control study. Cancer Epidemiol Biomarkers Prev. 2008;17:959–65.

    Article  PubMed  Google Scholar 

  21. 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;13:27–34.

    Article  PubMed  Google Scholar 

  22. Mayoral W, Salcedo J, Al-Kawas F. Ampullary carcinoid tumor presenting as acute pancreatitis in a patient with von Recklinghausen’s disease: case report and review of the literature. Endoscopy. 2003;35:854–7.

    Article  CAS  PubMed  Google Scholar 

  23. Halfdanarson TR, Bamlet WR, McWilliams RR, et al. Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study. Pancreas. 2014;43:1219–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hiripi E, Bermejo JL, Sundquist J, Hemminki K. Familial gastrointestinal carcinoid tumours and associated cancers. Ann Oncol. 2009;20:950–4.

    Article  CAS  PubMed  Google Scholar 

  25. Konishi T, Watanabe T, Kishimoto J, Kotake K, Muto T, Nagawa H. Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut. 2007;56:863–8.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Jung YS, Yun KE, Chang Y, et al. Risk factors associated with rectal neuroendocrine tumors: a cross-sectional study. Cancer Epidemiol Biomarkers Prev. 2014;23:1406–13.

    Article  CAS  PubMed  Google Scholar 

  27. Giovannucci E, Goldin B. The role of fat, fatty acids, and total energy intake in the etiology of human colon cancer. Am J Clin Nutr. 1997;66:1564s–71s.

    CAS  PubMed  Google Scholar 

  28. Esposito K, Chiodini P, Capuano A, et al. Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis. Endocrine. 2013;44:634–47.

    Article  CAS  PubMed  Google Scholar 

  29. Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. 2007;86:s836–42.

    PubMed  Google Scholar 

  30. Kesse E, Clavel-Chapelon F, Boutron-Ruault MC. Dietary patterns and risk of colorectal tumors: a cohort of French women of the National Education System (E3 N). Am J Epidemiol. 2006;164:1085–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Norat T, Bingham S, Ferrari P, et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst. 2005;97:906–16.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Slattery ML, Boucher KM, Caan BJ, Potter JD, Ma KN. Eating patterns and risk of colon cancer. Am J Epidemiol. 1998;148:4–16.

    Article  CAS  PubMed  Google Scholar 

  33. Norat T, Lukanova A, Ferrari P, Riboli E. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer. 2002;98:241–56.

    Article  CAS  PubMed  Google Scholar 

  34. Wells AM, Haub MD, Fluckey J, Williams DK, Chernoff R, Campbell WW. Comparisons of vegetarian and beef-containing diets on hematological indexes and iron stores during a period of resistive training in older men. J Am Diet Assoc. 2003;103:594–601.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ferrannini E. Insulin resistance, iron, and the liver. Lancet. 2000;355:2181–2.

    Article  CAS  PubMed  Google Scholar 

  36. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004;291:711–7.

    Article  CAS  PubMed  Google Scholar 

  37. Piperno A, Trombini P, Gelosa M, et al. Increased serum ferritin is common in men with essential hypertension. J Hypertens. 2002;20:1513–8.

    Article  CAS  PubMed  Google Scholar 

  38. Halle M, Konig D, Berg A, Keul J, Baumstark MW. Relationship of serum ferritin concentrations with metabolic cardiovascular risk factors in men without evidence for coronary artery disease. Atherosclerosis. 1997;128:235–40.

    Article  CAS  PubMed  Google Scholar 

  39. Gillum RF. Association of serum ferritin and indices of body fat distribution and obesity in Mexican American men—the Third National Health and Nutrition Examination Survey. Int J Obes Relat Metab Disord. 2001;25:639–45.

    Article  CAS  PubMed  Google Scholar 

  40. Mateo-Gallego R, Calmarza P, Jarauta E, Burillo E, Cenarro A, Civeira F. Serum ferritin is a major determinant of lipid phenotype in familial combined hyperlipidemia and familial hypertriglyceridemia. Metabolism. 2010;59:154–8.

    Article  CAS  PubMed  Google Scholar 

  41. Kim CH, Kim HK, Bae SJ, Park JY, Lee KU. Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women. Metabolism. 2011;60:414–20.

    Article  CAS  PubMed  Google Scholar 

  42. Simcox JA, McClain DA. Iron and diabetes risk. Cell Metab. 2013;17:329–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bartsch H, Nair J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg. 2006;391:499–510.

    Article  PubMed  Google Scholar 

  44. Berkovic MC, Jokic M, Marout J, Radosevic S, Zjacic-Rotkvic V, Kapitanovic S. IL-2 -330 T/G SNP and serum values—potential new tumor markers in neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NETs). J Mol Med (Berl). 2010;88:423–9.

  45. Garrelds IM, van Meeteren ME, Meijssen MA, Zijlstra FJ. Interleukin-2-deficient mice: effect on cytokines and inflammatory cells in chronic colonic disease. Dig Dis Sci. 2002;47:503–10.

  46. Yao JC, Hoff PM, Hoff AO, eds. Neuroendocrine tumors. New York: Humana, 2011.

  47. Debelenko LV, Zhuang Z, Emmert-Buck MR, et al. Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. Cancer Res. 1997;57:2238–43.

    CAS  PubMed  Google Scholar 

  48. Hammel PR, Vilgrain V, Terris B, et al. Pancreatic involvement in von Hippel–Lindau disease. The Groupe Francophone d’Etude de la Maladie de von Hippel-Lindau. Gastroenterology. 2000;119:1087–95.

  49. Lubensky IA, Pack S, Ault D, et al. Multiple neuroendocrine tumors of the pancreas in von Hippel–Lindau disease patients: histopathological and molecular genetic analysis. Am J Pathol. 1998;153:223–31.

  50. Cappelli C, Agosti B, Braga M, et al. Von Recklinghausen’s neurofibromatosis associated with duodenal somatostatinoma. A case report and review of the literature. Minerva Endocrinol. 2004;29:19–24.

    CAS  PubMed  Google Scholar 

  51. Yao JC. Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Pract Res Clin Endocrinol Metab. 2007;21:163–72.

    Article  CAS  PubMed  Google Scholar 

  52. Verhoef S, van Diemen-Steenvoorde R, Akkersdijk WL, et al. Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood. Eur J Pediatr. 1999;158:284–7.

    Article  CAS  PubMed  Google Scholar 

  53. Eledrisi MS, Stuart CA, Alshanti M. Insulinoma in a patient with tuberous sclerosis: is there an association? Endocr Pract. 2002;8:109–12.

    Article  PubMed  Google Scholar 

  54. Katdare MV, Fichera A, Heimann TM. Familial rectal carcinoid: report of two first-degree relatives with rectal carcinoid and review of the literature. Tech Coloproctol. 2006;10:143–6.

    Article  CAS  PubMed  Google Scholar 

  55. Holland PW, Rubin DB. Causal inference in retrospective studies. Eval Rev. 1988;12:203–31.

    Article  Google Scholar 

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Acknowledgments

This study was supported by Samsung Medical Center Grant [#SMO1131951].

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Authors and Affiliations

  1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea

    Jeung Hui Pyo, Sung Noh Hong, Byung-Hoon Min, Jun Haeng Lee, Dong Kyung Chang, Poong-Lyul Rhee, Jae Jun Kim, Hee Jung Son & Young-Ho Kim

  2. Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Sun Kyu Choi & Sin-Ho Jung

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  1. Jeung Hui Pyo
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Pyo, J.H., Hong, S.N., Min, BH. et al. Evaluation of the risk factors associated with rectal neuroendocrine tumors: a big data analytic study from a health screening center. J Gastroenterol 51, 1112–1121 (2016). https://doi.org/10.1007/s00535-016-1198-9

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  • DOI: https://doi.org/10.1007/s00535-016-1198-9

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