Skip to main content

Advertisement

SpringerLink
Log in

Inverse relationship between cancer and Alzheimer’s disease: a systemic review meta-analysis

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) and cancer are both prevalent in the elderly. Some epidemiological researches have reported the negative association between AD and cancer, but the results are controversial. The present meta-analysis is aimed to clarify the association between cancer and AD. PubMed, Web of knowledge and the Cochrane library databases were searched for eligible publications. The analysis indicated that history of cancer was associated with a reduced risk of AD (ES 0.62, 95 % CIs 0.53–0.74; p < 0.001), with no significance between-study heterogeneity and publication bias. Similar results were found in subgroup analysis by stratifying variables with education and APOEε4 carriers, years of follow-up and sample size of cases. The negative association was also found in analysis of risk of cancer among patients with AD (ES 0.59, 95 % CIs 0.42–0.82; p = 0.002), but with evidence of between-study heterogeneity and publication bias. In order to identify sources of the heterogeneity, subgroup analysis was performed by stratifying variable with or without education adjusted, sample size of cases and years of follow-up. Negative association was found in all subgroup analysis except in studies with less than 5-year follow-up and with heterogeneity disappeared only in the subgroup analysis stratified with sample size of cases. Our results in the present meta-analysis support the negative association between AD and cancer. But further well-designed perspective studies with strict control of confounding factors are needed to clarify the association between AD and cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Loy CT, Schofield PR, Turner AM, Kwok JBJ (2014) Genetics of dementia. Lancet 383(9919):828–840. doi:10.1016/s0140-6736(13)60630-3

    Article  CAS  PubMed  Google Scholar 

  2. Thies W, Bleiler L (2013) 2013 Alzheimer’s disease facts and figures. Alzheimer Dement 9(2):208–245. doi:10.1016/j.jalz.2013.02.003

    Article  Google Scholar 

  3. Huang Y, Mucke L (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148(6):1204–1222. doi:10.1016/j.cell.2012.02.040

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Catala-Lopez F, Suarez-Pinilla M, Suarez-Pinilla P, Valderas JM, Gomez-Beneyto M, Martinez S, Balanza-Martinez V, Climent J, Valencia A, McGrath J, Crespo-Facorro B, Sanchez-Moreno J, Vieta E, Tabares-Seisdedos R (2014) 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 83(2):89–105. doi:10.1159/000356498

    Article  PubMed  Google Scholar 

  5. Bajaj A, Driver JA, Schernhammer ES (2010) Parkinson’s disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control 21(5):697–707. doi:10.1007/s10552-009-9497-6

    Article  PubMed  Google Scholar 

  6. Ibanez K, Boullosa C, Tabares-Seisdedos R, Baudot A, Valencia A (2014) Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. PLoS Genet 10(2):e1004173. doi:10.1371/journal.pgen.1004173

    Article  PubMed Central  PubMed  Google Scholar 

  7. Lai SW, Chen HJ, Lin CL, Liao KF (2014) No correlation between Alzheimer’s disease and risk of hepatocellular carcinoma in older people: an observation in Taiwan. Geriatr Gerontol Int 14(1):231–232. doi:10.1111/ggi.12141

    Article  PubMed  Google Scholar 

  8. White RS, Lipton RB, Hall CB, Steinerman JR (2013) Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology 80(21):1966–1972. doi:10.1212/WNL.0b013e3182941990

    Article  PubMed Central  PubMed  Google Scholar 

  9. Ou SM, Lee YJ, Hu YW, Liu CJ, Chen TJ, Fuh JL, Wang SJ (2013) Does Alzheimer’s disease protect against cancers? A nationwide population-based study. Neuroepidemiology 40(1):42–49. doi:10.1159/000341411

    Article  PubMed  Google Scholar 

  10. Musicco M, Adorni F, Di Santo S, Prinelli F, Pettenati C, Caltagirone C, Palmer K, Russo A (2013) Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology 81(4):322–328. doi:10.1212/WNL.0b013e31829c5ec1

    Article  PubMed  Google Scholar 

  11. Driver JA, Beiser A, Au R, Kreger BE, Splansky GL, Kurth T, Kiel DP, Lu KP, Seshadri S, Wolf PA (2012) Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ 344:e1442

    Article  PubMed Central  PubMed  Google Scholar 

  12. Roe CM, Fitzpatrick AL, Xiong C, Sieh W, Kuller L, Miller JP, Williams MM, Kopan R, Behrens MI, Morris JC (2010) Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74(2):106–112. doi:10.1212/WNL.0b013e3181c91873

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Roe CM, Behrens MI, Xiong C, Miller JP, Morris JC (2005) Alzheimer disease and cancer. Neurology 64(5):895–898. doi:10.1212/01.wnl.0000152889.94785.51

    Article  CAS  PubMed  Google Scholar 

  14. Yamada M, Sasaki H, Mimori Y, Kasagi F, Sudoh S, Ikeda J, Hosoda Y, Nakamura S, Kodama K (1999) Prevalence and risks of dementia in the Japanese population: RERF’s adult health study Hiroshima subjects. Radiation Effects Research Foundation. J Am Geriatr Soc 47(2):189–195

    Article  CAS  PubMed  Google Scholar 

  15. Ganguli M (2012) A reduced risk of Alzheimer’s disease in those who survive cancer. BMJ 344:e1662

    Article  PubMed  Google Scholar 

  16. DeSouky AL (1992) The relationship between cancer and Alzheimer’s disease. J Am Geriatr Soc 40(10):1075

    Article  CAS  PubMed  Google Scholar 

  17. Driver JA, Yung R, Gaziano JM, Kurth T (2010) Chronic disease in men with newly diagnosed cancer: a nested case–control study. Am J Epidemiol 172(3):299–308. doi:10.1093/aje/kwq127

    Article  PubMed Central  PubMed  Google Scholar 

  18. Attner B, Lithman T, Noreen D, Olsson H (2010) Low cancer rates among patients with dementia in a population-based register study in Sweden. Dement Geriatr Cogn Disord 30(1):39–42. doi:10.1159/000315509

    Article  PubMed  Google Scholar 

  19. Hototian SR, Lopes MA, Azevedo D, Tatsch M, Bazzarella MC, Bustamante SE, Litvoc J, Bottino CM (2008) Prevalence of cognitive and functional impairment in a community sample from Sao Paulo, Brazil. Dement Geriatr Cogn Disord 25(2):135–143. doi:10.1159/000112554

    Article  PubMed  Google Scholar 

  20. Realmuto S, Cinturino A, Arnao V, Mazzola MA, Cupidi C, Aridon P, Ragonese P, Savettieri G, D’Amelio M (2012) Tumor diagnosis preceding Alzheimer’s disease onset: is there a link between cancer and Alzheimer’s disease? J Alzheimers Dis 31(1):177–182. doi:10.3233/jad-2012-120184

    CAS  PubMed  Google Scholar 

  21. Burke WJ, McLaughlin JR, Chung HD, Gillespie KN, Grossberg GT, Luque FA, Zimmerman J (1994) Occurrence of cancer in Alzheimer and elderly control patients: an epidemiologic necropsy study. Alzheimer Dis Assoc Disord 8(1):22–28

    Article  CAS  PubMed  Google Scholar 

  22. Desai MM, Bruce ML, Desai RA, Druss BG (2001) Validity of self-reported cancer history: a comparison of health interview data and cancer registry records. Am J Epidemiol 153(3):299–306

    Article  CAS  PubMed  Google Scholar 

  23. Hodgson KD, Hutchinson AD, Wilson CJ, Nettelbeck T (2013) A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. Cancer Treat Rev 39(3):297–304. doi:10.1016/j.ctrv.2012.11.001

    Article  CAS  PubMed  Google Scholar 

  24. Surma-aho O, Niemela M, Vilkki J, Kouri M, Brander A, Salonen O, Paetau A, Kallio M, Pyykkonen J, Jaaskelainen J (2001) Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients. Neurology 56(10):1285–1290

    Article  CAS  PubMed  Google Scholar 

  25. Caamano-Isorna F, Corral M, Montes-Martinez A, Takkouche B (2006) Education and dementia: a meta-analytic study. Neuroepidemiology 26(4):226–232. doi:10.1159/000093378

    Article  PubMed  Google Scholar 

  26. Roe CM, Xiong C, Miller JP, Morris JC (2007) Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology 68(3):223–228. doi:10.1212/01.wnl.0000251303.50459.8a

    Article  PubMed  Google Scholar 

  27. Tanzi RE, Bertram L (2005) Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120(4):545–555. doi:10.1016/j.cell.2005.02.008

    Article  CAS  PubMed  Google Scholar 

  28. Driver JA, Lu KP (2010) Pin1: a new genetic link between Alzheimer’s disease, cancer and aging. Curr Aging Sci 3(3):158–165

    Article  CAS  PubMed  Google Scholar 

  29. Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP (2006) The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440(7083):528–534. doi:10.1038/nature04543

    Article  CAS  PubMed  Google Scholar 

  30. Liou YC, Sun A, Ryo A, Zhou XZ, Yu ZX, Huang HK, Uchida T, Bronson R, Bing G, Li X, Hunter T, Lu KP (2003) Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424(6948):556–561. doi:10.1038/nature01832

    Article  CAS  PubMed  Google Scholar 

  31. van Heemst D, Mooijaart SP, Beekman M, Schreuder J, de Craen AJ, Brandt BW, Slagboom PE, Westendorp RG (2005) Variation in the human TP53 gene affects old age survival and cancer mortality. Exp Gerontol 40(1–2):11–15

    Article  PubMed  Google Scholar 

  32. Behrens MI, Lendon C, Roe CM (2009) A common biological mechanism in cancer and Alzheimer’s disease? Curr Alzheimer Res 6(3):196–204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Holohan KN, Lahiri DK, Schneider BP, Foroud T, Saykin AJ (2012) Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways. Front Genet 3:323. doi:10.3389/fgene.2012.00323

    PubMed Central  PubMed  Google Scholar 

  34. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Method 1(2):97–111. doi:10.1002/jrsm.12

    Article  Google Scholar 

  35. Rothstein HR, Sutton AJ, Borenstein M (2006) Publication bias in meta-analysis: prevention, assessment and adjustments. John Wiley & Sons

Download references

Acknowledgments

We thank Dr. Shumei Wang, professor of Department of Epidemiology and Health Statistics in Shandong University, for data analysis advice.

Conflict of interest

All authors declare no financial competing interests. All authors declare no non-financial competing interests.

Author information

Authors and Affiliations

  1. Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People’s Republic of China

    Qinghua Zhang, Shougang Guo, Xiao Zhang, Shi Tang, Wen Shao, Xiaojuan Han, Lu Wang & Yifeng Du

Authors
  1. Qinghua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shougang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaojuan Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yifeng Du
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yifeng Du.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Guo, S., Zhang, X. et al. Inverse relationship between cancer and Alzheimer’s disease: a systemic review meta-analysis. Neurol Sci 36, 1987–1994 (2015). https://doi.org/10.1007/s10072-015-2282-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-015-2282-2

Keywords

Search

Navigation