Skip to main content

Advertisement

SpringerLink
Log in

Alzheimer disease and cancer risk: a meta-analysis

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 28 August 2014

A Letter to the Editor to this article was published on 21 August 2014

Abstract

Purpose

Alzheimer disease (AD) and cancer are seemingly two opposite ends of one spectrum. Studies have suggested that patients with AD showed a reduced risk of cancer and vice versa. However, available evidences are not conclusive. So we conducted a meta-analysis using published literatures to systematically examine cancer risk in AD patients.

Methods

A PubMed, EMBASE, and Web of Science search were conducted in May 2014. Pooled risk ratios (RRs) with their corresponding 95 % confidence intervals (CIs) were obtained using random-effects meta-analysis. We tested for publication bias and heterogeneity, and stratified for study characteristics, smoking-related cancers versus nonsmoking-related cancers, and site-specific cancers.

Results

Nine studies were included in this meta-analysis. Compared with controls, the pooled RR of cancer in AD patients was 0.55 (95 % CI 0.41–0.75), with significant heterogeneity among these studies (P < 0.001, I 2 = 83.5 %). The reduced cancer risk was more substantial when we restricted analyses to cohort studies, studies with adjusted estimates, studies defining AD by generally accepted criteria, and studies with longer length of follow-up. In sub-analyses for site-specific cancers, only lung cancer showed significant decreased risk (RR 0.72; 95 % CI 0.56–0.91). We did not find significant publication bias (P = 0.251 for Begg and Mazumdar’s test and P = 0.143 for Egger’s regression asymmetry test).

Conclusion

These results support an association between AD and decreased cancer risk.

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

Similar content being viewed by others

References

  • Anstey KJ, von Sanden C, Salim A, O’Kearney R (2007) Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am J Epidemiol 166(4):367–378. doi:10.1093/aje/kwm116

    Article  PubMed  Google Scholar 

  • 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 

  • Baker FM, Jordan B, Barclay L, Schoenberg BS (1993) Risk factors for clinically diagnosed Alzheimer’s disease. Int J Geriatr Psychiatry 8(5):379–385

    Article  Google Scholar 

  • Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, Zhang H, Li Z (2011) Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur J Cancer (Oxford Engl 1990) 47(13):1928–1937. doi:10.1016/j.ejca.2011.03.003

  • Chen RJ, Ho YS, Guo HR, Wang YJ (2008) Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells. Toxicol Sci Off J Soc Toxicol 104(2):283–293. doi:10.1093/toxsci/kfn086

    Article  CAS  Google Scholar 

  • Dash SK (2013) Cognitive impairment and diabetes. Recent Pat Endocr Metab Immune Drug Discov 7(2):155–165

    Article  CAS  PubMed  Google Scholar 

  • DePinho RA (2000) The age of cancer. Nature 408(6809):248–254. doi:10.1038/35041694

    Article  CAS  PubMed  Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  • Driver JA (2012) Understanding the link between cancer and neurodegeneration. J Geriatr Oncol 3(1):58–67. doi:10.1016/j.jgo.2011.11.007

    Article  Google Scholar 

  • 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 Clin Res Ed 344:e1442. doi:10.1136/bmj.e1442

    Article  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ Clin Res Ed 315(7109):629–634

    Article  CAS  Google Scholar 

  • Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159. doi:10.1056/NEJMra072067

    Article  CAS  PubMed  Google Scholar 

  • Galliot B, Tanaka E, Simon A (2008) Regeneration and tissue repair: themes and variations. Cell Mol Life Sci 65(1):3–7. doi:10.1007/s00018-007-7424-0

    Article  CAS  PubMed  Google Scholar 

  • Ganguli M, Dodge HH (2006) Mortality and survival in Alzheimer’s disease: a 15-year community study. Res Pract Alzheimer’s Dis 11:277–283

  • Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST (2005) Alzheimer disease and mortality: a 15-year epidemiological study. Arch Neurol 62(5):779–784

    Article  PubMed  Google Scholar 

  • Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309

    CAS  PubMed  Google Scholar 

  • Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ Clin Res Ed 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  Google Scholar 

  • Imfeld P, Bodmer M, Schuerch M, Jick SS, Meier CR (2013) Seizures in patients with Alzheimer’s disease or vascular dementia: a population-based nested case–control analysis. Epilepsia 54(4):700–707. doi:10.1111/epi.12045

    Article  CAS  PubMed  Google Scholar 

  • Jagger C, Clarke M, Stone A (1995) Predictors of survival with Alzheimer’s disease: a community-based study. Psychol Med 25(1):171–177

    Article  CAS  PubMed  Google Scholar 

  • Jope RS, Yuskaitis CJ, Beurel E (2007) Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res 32(4–5):577–595. doi:10.1007/s11064-006-9128-5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jorm AF, Jolley D (1998) The incidence of dementia—a meta-analysis. Neurology 51(3):728–733

    Article  CAS  PubMed  Google Scholar 

  • Kokmen E, Beard CM, Chandra V, Offord KP, Schoenberg BS, Ballard DJ (1991) Clinical risk-factors for Alzheimers-disease—a population-based case–control study. Neurology 41(9):1393–1397

    Article  CAS  PubMed  Google Scholar 

  • Lau JK, Brown KC, Thornhill BA, Crabtree CM, Dom AM, Witte TR, Hardman WE, McNees CA, Stover CA, Carpenter AB, Luo H, Chen YC, Shiflett BS, Dasgupta P (2013) Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma. Cancer Res 73(4):1328–1339. doi:10.1158/0008-5472.can-12-3190

    Article  CAS  PubMed  Google Scholar 

  • Lee CH, Huang CS, Chen CS, Tu SH, Wang YJ, Chang YJ, Tam KW, Wei PL, Cheng TC, Chu JS, Chen LC, Wu CH, Ho YS (2010) Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells. J Natl Cancer Inst 102(17):1322–1335. doi:10.1093/jnci/djq300

    Article  CAS  PubMed  Google Scholar 

  • Li T, Wen H, Brayton C, Laird FM, Ma G, Peng S, Placanica L, Wu TC, Crain BJ, Price DL, Eberhart CG, Wong PC (2007) Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci Off J Soc Neurosci 27(40):10849–10859. doi:10.1523/jneurosci.2152-07.2007

    Article  CAS  Google Scholar 

  • Manly JJ, Merchant CA, Jacobs DM, Small SA, Bell K, Ferin M, Mayeux R (2000) Endogenous estrogen levels and Alzheimer’s disease among postmenopausal women. Neurology 54(4):833–837

    Article  CAS  PubMed  Google Scholar 

  • Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD (2009) Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PLoS One 4(8):e6617. doi:10.1371/journal.pone.0006617

    Article  PubMed Central  PubMed  Google Scholar 

  • Mehler MF (2008) Epigenetics and the nervous system. Ann Neurol 64(6):602–617. doi:10.1002/ana.21595

    Article  CAS  PubMed  Google Scholar 

  • Migliore L, Coppede F (2002) Genetic and environmental factors in cancer and neurodegenerative diseases. Mutat Res 512(2–3):135–153

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Nery AA, Resende RR, Martins AH, Trujillo CA, Eterovic VA, Ulrich H (2010) Alpha 7 nicotinic acetylcholine receptor expression and activity during neuronal differentiation of PC12 pheochromocytoma cells. J Mol Neurosci 41(3):329–339. doi:10.1007/s12031-010-9369-2

    Article  CAS  PubMed  Google Scholar 

  • Nordberg A (1994) Human nicotinic receptors—their role in aging and dementia. Neurochem Int 25(1):93–97

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Paradise M, Walker Z, Cooper C, Blizard R, Regan C, Katona C, Livingston G (2009) Prediction of survival in Alzheimer’s disease—the LASER-AD longitudinal study. Int J Geriatr Psychiatry 24(7):739–747. doi:10.1002/gps.2190

    Article  PubMed  Google Scholar 

  • Plun-Favreau H, Lewis PA, Hardy J, Martins LM, Wood NW (2010) Cancer and neurodegeneration: between the devil and the deep blue sea. PLoS Genet 6(12):e1001257. doi:10.1371/journal.pgen.1001257

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Power MC, Weuve J, Gagne JJ, McQueen MB, Viswanathan A, Blacker D (2011) The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis. Epidemiology 22(5):646–659. doi:10.1097/EDE.0b013e31822708b5

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 Alzheimer’s Dis 31(1):177–182. doi:10.3233/jad-2012-120184

    CAS  Google Scholar 

  • Roe CM, Behrens MI (2013) AD and cancer: epidemiology makes for strange bedfellows. Neurology 81(4):310–311. doi:10.1212/WNL.0b013e31829c5f16

    Article  PubMed  Google Scholar 

  • 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 

  • 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 

  • Schuller HM (2009) Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 9(3):195–205. doi:10.1038/nrc2590

    Article  CAS  PubMed  Google Scholar 

  • Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. doi:10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  • Staropoli JF (2008) Tumorigenesis and neurodegeneration: two sides of the same coin? Bioessays News Rev Mol Cell Dev Biol 30(8):719–727. doi:10.1002/bies.20784

    Article  CAS  Google Scholar 

  • Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. J Am Med Assoc 283(15):2008–2012

    Article  CAS  Google Scholar 

  • Takahashi K, Uchida C, Shin RW, Shimazaki K, Uchida T (2008) Prolyl isomerase, Pin1: new findings of post-translational modifications and physiological substrates in cancer, asthma and Alzheimer’s disease. Cell Mol Life Sci 65(3):359–375. doi:10.1007/s00018-007-7270-0

    Article  CAS  PubMed  Google Scholar 

  • The Health Consequences of Smoking: A Report of the Surgeon General (2004). Atlanta GA

  • Tsai PH, Chen SP, Lin KN, Wang PN, Wang HC, Liu CY, Hong CJ, Liu HC (2007) Survival of ethnic Chinese with Alzheimer’s disease: a 5-year longitudinal study in Taiwan. J Geriatr Psychiatry Neurol 20(3):172–177. doi:10.1177/0891988707301864

    Article  PubMed  Google Scholar 

  • Ubhi K, Masliah E (2013) Alzheimer’s disease: recent advances and future perspectives. J Alzheimer’s Dis 33(Suppl 1):S185–S194. doi:10.3233/jad-2012-129028

    Google Scholar 

  • van Dijk PT, Dippel DW, Habbema JD (1991) Survival of patients with dementia. J Am Geriatr Soc 39(6):603–610

    PubMed  Google Scholar 

  • Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8(4):275–283. doi:10.1038/nrm2147

    Article  CAS  PubMed  Google Scholar 

  • Walker A (1991) Observation and Inference: An introduction to the methods of epidemiology. Epidemiology Resources Inc, Newton Lower Falls

    Google Scholar 

  • Warpman U, Nordberg A (1995) Epibatidine and ABT 418 reveal selective losses of alpha 4 beta 2 nicotinic receptors in Alzheimer brains. Neuroreport 6(17):2419–2423

    Article  CAS  PubMed  Google Scholar 

  • Wevers A, Schroder H (1999) Nicotinic acetylcholine receptors in Alzheimer’s disease. J Alzheimer’s Dis 1(4–5):207–219

    CAS  Google Scholar 

  • 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 

  • Wu CH, Lee CH, Ho YS (2011) Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy. Clin Cancer Res Off J Am Assoc Cancer Res 17(11):3533–3541. doi:10.1158/1078-0432.ccr-10-2434

    Article  CAS  Google Scholar 

  • Zanetti O, Solerte SB, Cantoni F (2009) Life expectancy in Alzheimer’s disease (AD). Arch Gerontol Geriatr 49(Suppl 1):237–243. doi:10.1016/j.archger.2009.09.035

    Article  PubMed  Google Scholar 

  • Zhao Y, Shen L, Ji HF (2012) Alzheimer’s disease and risk of hip fracture: a meta-analysis study. Sci World J 2012:872173. doi:10.1100/2012/872173

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China Grants (81220108010 and 81171197) and Bureau of Health of Chongqing Medical Research Grant (2011-1-018) to G-J. Chen.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Hai-bin Shi, Bo Tang, Yao-Wen Liu, Xue-Feng Wang & Guo-Jun Chen

Authors
  1. Hai-bin Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yao-Wen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xue-Feng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guo-Jun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guo-Jun Chen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, Hb., Tang, B., Liu, YW. et al. Alzheimer disease and cancer risk: a meta-analysis. J Cancer Res Clin Oncol 141, 485–494 (2015). https://doi.org/10.1007/s00432-014-1773-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1773-5

Keywords

Search

Navigation