Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 3/2015

01-03-2015 | Review – Clinical Oncology

Alzheimer disease and cancer risk: a meta-analysis

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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2015

Login to get access

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.
Literature
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference Baker FM, Jordan B, Barclay L, Schoenberg BS (1993) Risk factors for clinically diagnosed Alzheimer’s disease. Int J Geriatr Psychiatry 8(5):379–385CrossRef Baker FM, Jordan B, Barclay L, Schoenberg BS (1993) Risk factors for clinically diagnosed Alzheimer’s disease. Int J Geriatr Psychiatry 8(5):379–385CrossRef
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefPubMed Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefPubMed
go back to reference 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 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
go back to reference 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 CrossRef 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 CrossRef
go back to reference Dash SK (2013) Cognitive impairment and diabetes. Recent Pat Endocr Metab Immune Drug Discov 7(2):155–165CrossRefPubMed Dash SK (2013) Cognitive impairment and diabetes. Recent Pat Endocr Metab Immune Drug Discov 7(2):155–165CrossRefPubMed
go back to reference 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 CrossRef 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 CrossRef
go back to reference 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):629–634CrossRef 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):629–634CrossRef
go back to reference 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 (2006) Mortality and survival in Alzheimer’s disease: a 15-year community study. Res Pract Alzheimer’s Dis 11:277–283
go back to reference Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST (2005) Alzheimer disease and mortality: a 15-year epidemiological study. Arch Neurol 62(5):779–784CrossRefPubMed Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST (2005) Alzheimer disease and mortality: a 15-year epidemiological study. Arch Neurol 62(5):779–784CrossRefPubMed
go back to reference Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309PubMed Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309PubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference Jagger C, Clarke M, Stone A (1995) Predictors of survival with Alzheimer’s disease: a community-based study. Psychol Med 25(1):171–177CrossRefPubMed Jagger C, Clarke M, Stone A (1995) Predictors of survival with Alzheimer’s disease: a community-based study. Psychol Med 25(1):171–177CrossRefPubMed
go back to reference 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):1393–1397CrossRefPubMed 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):1393–1397CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRef 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 CrossRef
go back to reference 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):833–837CrossRefPubMed 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):833–837CrossRefPubMed
go back to reference Migliore L, Coppede F (2002) Genetic and environmental factors in cancer and neurodegenerative diseases. Mutat Res 512(2–3):135–153CrossRefPubMed Migliore L, Coppede F (2002) Genetic and environmental factors in cancer and neurodegenerative diseases. Mutat Res 512(2–3):135–153CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference Nordberg A (1994) Human nicotinic receptors—their role in aging and dementia. Neurochem Int 25(1):93–97CrossRefPubMed Nordberg A (1994) Human nicotinic receptors—their role in aging and dementia. Neurochem Int 25(1):93–97CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 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
go back to reference 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):2008–2012CrossRef 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):2008–2012CrossRef
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference The Health Consequences of Smoking: A Report of the Surgeon General (2004). Atlanta GA The Health Consequences of Smoking: A Report of the Surgeon General (2004). Atlanta GA
go back to reference 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 CrossRefPubMed 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​ CrossRefPubMed
go back to reference van Dijk PT, Dippel DW, Habbema JD (1991) Survival of patients with dementia. J Am Geriatr Soc 39(6):603–610PubMed van Dijk PT, Dippel DW, Habbema JD (1991) Survival of patients with dementia. J Am Geriatr Soc 39(6):603–610PubMed
go back to reference Walker A (1991) Observation and Inference: An introduction to the methods of epidemiology. Epidemiology Resources Inc, Newton Lower Falls Walker A (1991) Observation and Inference: An introduction to the methods of epidemiology. Epidemiology Resources Inc, Newton Lower Falls
go back to reference 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):2419–2423CrossRefPubMed 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):2419–2423CrossRefPubMed
go back to reference Wevers A, Schroder H (1999) Nicotinic acetylcholine receptors in Alzheimer’s disease. J Alzheimer’s Dis 1(4–5):207–219 Wevers A, Schroder H (1999) Nicotinic acetylcholine receptors in Alzheimer’s disease. J Alzheimer’s Dis 1(4–5):207–219
Metadata
Title
Alzheimer disease and cancer risk: a meta-analysis
Authors
Hai-bin Shi
Bo Tang
Yao-Wen Liu
Xue-Feng Wang
Guo-Jun Chen
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1773-5

Other articles of this Issue 3/2015

Journal of Cancer Research and Clinical Oncology 3/2015 Go to the issue