Dement Neurocogn Disord.  2018 Dec;17(4):137-147. 10.12779/dnd.2018.17.4.137.

Association between Alzheimer's Disease and Cancer Risk in South Korea: an 11-year Nationwide Population-Based Study

• Lee JE
• Kim D
• Lee JH

• KMID: 2442784
• DOI: http://doi.org/10.12779/dnd.2018.17.4.137

Abstract

BACKGROUND AND PURPOSE
Previous studies have suggested a decreased cancer risk among patients with Alzheimer's disease (AD). There remains a lack of data on the specific types of cancer and risk factors for developing cancer in AD. We evaluated the association between AD and cancer risk, and we examined specific types of cancer.
METHODS
A population-based longitudinal study was conducted using the National Health Insurance Service-Senior cohort for 2002-2013. A total of 4,408 AD patients were included in the study, as were 19,150 matched controls. Potential associations between the risk of cancer and AD were analyzed using Cox proportional hazard regressions.
RESULTS
Cancer developed in 12.3% of the AD group patients and in 18.5% of control group subjects. AD was associated with a reduced risk of cancer (hazard ratio [HR], 0.70; 95% confidence intervals, 0.64-0.78). The risk of head and neck cancers was significantly reduced (HR, 0.49), as were risks for cancers of the digestive tract, including stomach cancer (HR, 0.42), colorectal cancer (HR, 0.61), liver and biliary tract cancers (HR, 0.68), and pancreatic cancer (HR, 0.55). Lung and prostate cancer risks were also significantly lower for the AD group (HR, 0.52 and HR, 0.72, respectively).
CONCLUSIONS
Our results showed an inverse association between AD and cancer. Further research involving a large number of patients in a hospital based-study is needed to address the biological associations between cancer development and dementia, including AD.

Keyword

Alzheimer's Disease; Epidemiology; Cancer

MeSH Terms

Alzheimer Disease*
Biliary Tract Neoplasms
Cohort Studies
Colorectal Neoplasms
Dementia
Epidemiology
Gastrointestinal Tract
Head
Humans
Korea*
Liver
Longitudinal Studies
Lung
National Health Programs
Neck
Pancreatic Neoplasms
Prostatic Neoplasms
Risk Factors
Stomach Neoplasms

Figure

• 

  Fig. 1 Definition of study cohorts. Among NHIS-Senior 2002–2013 data, the patients diagnosed with AD in 2002 were excluded (wash-out period). The patients diagnosed with AD (n=4,408) in the 3 years period from January 2003 to December 2005 (index period) and the control group (n=19,150) extracted using propensity score matching, were enrolled. During an 11-year follow-up period, the risk of cancers between the 2 groups was analyzed. NHIS-Senior: National Health Insurance Service-Senior, AD: Alzheimer's disease.

• 

  Fig. 2 Kaplan-Meier survival analysis for patients with and without AD who developed cancer. AD: Alzheimer's disease.

Reference

1. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003; 60:1119–1122.

2. Ma LL, Yu JT, Wang HF, Meng XF, Tan CC, Wang C, et al. Association between cancer and Alzheimer's disease: systematic review and meta-analysis. J Alzheimers Dis. 2014; 42:565–573.

3. Kukull WA, Ganguli M. Epidemiology of dementia: concepts and overview. Neurol Clin. 2000; 18:923–950.

4. Ou SM, Lee YJ, Hu YW, Liu CJ, Chen TJ, Fuh JL, et al. Does Alzheimer's disease protect against cancers? A nationwide population-based study. Neuroepidemiology. 2013; 40:42–49.

5. Hoskin DW, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta. 2008; 1778:357–375.

6. Schuller HM. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer. 2009; 9:195–205.

7. Roe CM, Behrens MI, Xiong C, Miller JP, Morris JC. Alzheimer disease and cancer. Neurology. 2005; 64:895–898.

8. Roe CM, Fitzpatrick AL, Xiong C, Sieh W, Kuller L, Miller JP, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology. 2010; 74:106–112.

9. Musicco M, Adorni F, Di Santo S, Prinelli F, Pettenati C, Caltagirone C, et al. Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology. 2013; 81:322–328.

10. Driver JA, Beiser A, Au R, Kreger BE, Splansky GL, Kurth T, et al. Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ. 2012; 344:e1442.

11. Shi HB, Tang B, Liu YW, Wang XF, Chen GJ. Alzheimer disease and cancer risk: a meta-analysis. J Cancer Res Clin Oncol. 2015; 141:485–494.

12. Realmuto S, Cinturino A, Arnao V, Mazzola MA, Cupidi C, Aridon P, et al. Tumor diagnosis preceding Alzheimer's disease onset: is there a link between cancer and Alzheimer's disease? J Alzheimers Dis. 2012; 31:177–182.

13. Lin HL, Lin HC, Tseng YF, Chen SC, Hsu CY. Inverse association between cancer and dementia: a population-based registry study in Taiwan. Alzheimer Dis Assoc Disord. 2016; 30:118–122.

14. Frain L, Swanson D, Cho K, Gagnon D, Lu KP, Betensky RA, et al. Association of cancer and Alzheimer's disease risk in a national cohort of veterans. Alzheimers Dement. 2017; 13:1364–1370.

15. Attner B, Lithman T, Noreen D, Olsson H. Low cancer rates among patients with dementia in a population-based register study in Sweden. Dement Geriatr Cogn Disord. 2010; 30:39–42.

16. Yamada M, Sasaki H, Mimori Y, Kasagi F, Sudoh S, Ikeda J, et al. Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. J Am Geriatr Soc. 1999; 47:189–195.

17. Catalá-López F, Crespo-Facorro B, Vieta E, Valderas JM, Valencia A, Tabarés-Seisdedos R. Alzheimer's disease and cancer: current epidemiological evidence for a mutual protection. Neuroepidemiology. 2014; 42:121–122.

18. National Health Insurance Service. 2016 National Health Screening Statistical Yearbook. Wonju: National Health Insurance Service;2017. p. 1–860.

19. Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer. 2011; 47:1928–1937.

20. Wong G, Howard K, Tong A, Craig JC. Cancer screening in people who have chronic disease: the example of kidney disease. Semin Dial. 2011; 24:72–78.

21. Kornum JB, Sværke C, Thomsen RW, Lange P, Sørensen HT. Chronic obstructive pulmonary disease and cancer risk: a Danish nationwide cohort study. Respir Med. 2012; 106:845–852.

22. Bennett DA. Is there a link between cancer and Alzheimer disease? Neurology. 2010; 75:1216–1217.

23. Behrens MI, Lendon C, Roe CM. A common biological mechanism in cancer and Alzheimer's disease? Curr Alzheimer Res. 2009; 6:196–204.

24. Plun-Favreau H, Lewis PA, Hardy J, Martins LM, Wood NW. Cancer and neurodegeneration: between the devil and the deep blue sea. PLoS Genet. 2010; 6:e1001257.

25. Ibáñez K, Boullosa C, Tabarés-Seisdedos R, Baudot A, Valencia A. Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. PLoS Genet. 2014; 10:e1004173.

26. Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP, Wang DG. Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol. 2004; 164:1727–1737.

27. van Heemst D, Mooijaart SP, Beekman M, Schreuder J, de Craen AJ, Brandt BW, et al. Variation in the human TP53 gene affects old age survival and cancer mortality. Exp Gerontol. 2005; 40:11–15.

28. Inestrosa NC, Montecinos-Oliva C, Fuenzalida M. Wnt signaling: role in Alzheimer disease and schizophrenia. J Neuroimmune Pharmacol. 2012; 7:788–807.

29. Catalá-López F, Suárez-Pinilla M, Suárez-Pinilla P, Valderas JM, Gómez-Beneyto M, Martinez S, et al. Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies. Psychother Psychosom. 2014; 83:89–105.

30. Bajaj A, Driver JA, Schernhammer ES. Parkinson's disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control. 2010; 21:697–707.

31. Sun LM, Liang JA, Chang SN, Sung FC, Muo CH, Kao CH. Analysis of Parkinson's disease and subsequent cancer risk in Taiwan: a nationwide population-based cohort study. Neuroepidemiology. 2011; 37:114–119.

32. Kang YW, Na DL, Hahn SH. A validity study on the Korean mini-mental state examination (K-MMSE) in dementia patients. J Korean Neurol Assoc. 1997; 15:300–308.

33. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993; 43:2412–2414.

34. Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982; 139:1136–1139.