Incidence of Cancer Among Persons With Schizophrenia and Their Relatives
Open accessAbstract
BACKGROUND: It has repeatedly been reported that the risk for cancer in patients with schizophrenia is different from that of the general population, specifically a lower risk for lung cancer despite increased smoking. Confirmation of these associations could lead to hypotheses on shared risk or protective factors, either genetic or environmental. METHODS: From Finland's National Hospital Discharge and Disability Pension registers, Helsinki, we identified a cohort of 26 996 individuals born between 1940 and 1969 and treated for schizophrenia between 1969 and 1991. They were followed up for cancer from 1971 to 1996 by record linkage with the Finnish Cancer Registry, yielding 446 653 person-years at risk, and standardized incidence ratios (SIRs) were calculated. Likewise, 39 131 parents and 52 976 siblings of the patients with schizophrenia were followed up to explore familial genetic hypotheses on deviations in cancer risk. RESULTS: In patients with schizophrenia, an increased overall cancer risk was found (724 cases observed vs 619 expected; SIR, 1.17; 95% confidence interval [CI], 1.09-1.25). Half of the excess cases were attributable to lung cancer (SIR, 2.17; 95% CI, 1.78-2.60), and the strongest relative increase in risk was in pharyngeal cancer (SIR, 2.60; 95% CI, 1.25-4.77). Cancer incidence in siblings (SIR, 0.89; 95% CI, 0.83-0.94) and parents (SIR, 0.91; 95% CI, 0.89-0.93) was consistently lower than that in the general population. CONCLUSION: Although specific lifestyle factors, particularly tobacco smoking and alcohol consumption, probably account for the increased cancer risk in patients with schizophrenia, the decreased risk in relatives would be compatible with a postulated genetic risk factor for schizophrenia offering selective advantage to unaffected relatives.
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Other studies found an increased or no different overall risk of cancer in patients with schizophrenia compared to the general population.
“On the other hand, other studies found an increased (9,21,28,(449)(450)(451) or no different (292,419,452,453) overall risk of cancer in patients with schizophrenia compared to the general population.”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [449]
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“For example, some studies showed decreased risks of lung cancer in schizophrenia (53, 56) while others showed increased risks (58, 62).”
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BackgroundInflammation and the two-hit hypothesis of schizophrenia
Feigenson, K. A., Kusnecov, A., & Silverstein, S. M. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.006 · Cited by 280 · see citing works
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Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia
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Hippisley-Cox, J., Vinogradova, Y., Coupland, C., & Parker, C. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.12.1368 · Cited by 214 · see citing works
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InfluentialCapasso, R., Lineberry, T. W., Bostwick, J. M., Decker, P. A., & Sauver, J. L. S. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.10.005 · Cited by 201 · see citing works
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Insulin and Insulin-Like Growth Factor-1 Abnormalities in Antipsychotic-Naive Schizophrenia
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“The debate over whether cancer incidence is decreased in schizophrenia has been complex and is only now being addressed systematically (Catts et al., 2008; Bushe et al., 2009; Lichtermann et al., 2001).”
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ResultDetection and management of comorbidity in patients with schizophrenia
Green, A. I., Canuso, C. M., Brenner, M. J., & Wojcik, J. (2003) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(02)00014-x · Cited by 159 · see citing works
“Although this counterintuitive finding has led some investigators to speculate that schizophrenia may confer a selective advantage against cancer [165], this hypothesis is not yet substantiated [166].”
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“Conversely, Lichtermann et al.1 reported on a higher overall cancer risk, with nearly half of the excess cases attributable to lung cancer, yet the incidence of breast cancer was unchanged.”
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Substance Misuse in Patients with Schizophrenia
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“Although smokers with schizophrenia may have a lower incidence of respiratory cancers than other smokers,[17] recent work has indicated that people with schizophrenia have higher overall rates of smoking-related cancer than the general population,[18] simply because of the far higher prevalence of smoking amongst them.”
Rüther, T., Bobes, J., De Hert, M., Svensson, T. H., Mann, K., Batra, A., Gorwood, P., & Möller, H. J. (2014) · European Psychiatry · doi:10.1016/j.eurpsy.2013.11.002 · Cited by 149 · see citing works
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“Previous studies have reported a higher incidence of mortality secondary to respiratory cancer (Lawrence et al., 2000a,b; Lichtermann et al., 2001; Grinshpoon et al., 2005), whereas other studies have reported a lower risk, which is consistent with the present findings (Gulbinat et al., 1992;…”
BackgroundResultInfluentialRisk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969–1993
Dalton, S. O., Mellemkjær, L., Thomassen, L., Mortensen, P. B., & Johansen, C. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2004.11.009 · Cited by 142 · see citing works
“A decreased risk for prostate cancer was also observed in cohort studies in Denmark (Mortensen, 1989, 1994) and in Finland (Lichtermann et al., 2001).”
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Tobacco Use Among Individuals With Schizophrenia: What Role Has the Tobacco Industry Played?
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BackgroundA cohort study on mental disorders, stage of cancer at diagnosis and subsequent survival
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“Still others have found an increased risk of incidence or mortality.(4,5) Some of these discrepancies may be explained by differences between psychiatric diagnoses.”
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Cancer risk among users of neuroleptic medication: a population-based cohort study
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Tabarés‐Seisdedos, R., & Rubenstein, J. L. R. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3464 · Cited by 114 · see citing works
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The evolutionary paradox and the missing heritability of schizophrenia
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ResultThe role of the phosphatidylinositide 3-kinase–protein kinase B pathway in schizophrenia
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“Still others have found an increased risk of incidence or mortality (Brown et al., 2000; Kisely et al., 2008; Lichtermann et al., 2001).”
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Li, H., Li, J., Yu, X., Zheng, H., Sun, X., Lü, Y., Zhang, Y., Li, C., & Bi, X. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.08.065 · Cited by 96 · see citing works
“This is a novel finding that contradictsmost previous studies, which have found no differences in colorectal cancer risk between patients with schizophrenia and the general population (Lichtermann et al., 2001; Guo, 2008).”
InfluentialCancer and severe mental illness: Bi‐directional problems and potential solutions
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“In the Finnish registry, schizophrenia patients were observed to have an increased incidence of lung cancer.(4) In contrast, the WHO registry observed a decreased incidence of lung cancer among the Danish cohort, which was partly explained by the restriction of smoking in the facilities.”
ResultRepurposing psychiatric drugs as anti-cancer agents
Huang, J., Zhao, D., Liu, Z., & Liu, F. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.01.058 · Cited by 89 · see citing works
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Health behavior in psychiatric in‐patients compared with a German general population sample
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DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond
Markkanen, E., Meyer, U., & Dianov, G. L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060856 · Cited by 84 · see citing works
“, suggesting that female schizophrenic patients have a higher cancer risk than the general population for breast, cervical and endometrial cancers [47,48].”
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Hodgson, R. E., Wildgust, H. J., & Bushe, C. (2010) · Journal of Psychopharmacology · doi:10.1177/1359786810385489 · Cited by 83 · see citing works
“Lichtermann et al. (2001), using the Finnish Cancer Registry, observed a total of 446,653 subject years and found an increased cancer rate.”
MethodInfluentialBioactive lipids in schizophrenia
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“The lower incidence of depression in populations with high intake of marine or sea fish (rich in n-3 fatty acids) provides further support for the importance of life time intake of EFA and proneness to mental illness ( Lichtermann, Ekelund, Pukkala, Tanskanen, & Lonnqvist, 2001; Stoll, 2001; Hibbeln, 1998) although th…”
ResultTsoi, D. T.-Y., Porwal, M., & Webster, A. C. (2010) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.109.066019 · Cited by 78 · see citing works
Schizophrenia and breast cancer incidence
Bushe, C., Bradley, A. J., Wildgust, H. J., & Hodgson, R. E. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.07.012 · Cited by 77 · see citing works
“Three of the studies had a reported or estimated greater than 100,000 patient years of risk (Grinshpoon et al., 2005; Lichtermann et al., 2001; Dalton et al., 2005).”
InfluentialProstate Cancer and Neuroendocrine Differentiation: More Neuronal, Less Endocrine?
Grigore, A. D., Ben‐Jacob, E., & Farach‐Carson, M. C. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00037 · Cited by 76 · see citing works
“Following almost a century of observations, systematic nationwide studies conducted during the last three decades have revealed an intriguing association between schizophrenia and a reduced risk for cancer as compared to the general population (169–175), although two other nations reported no difference or even an inc…”
BackgroundPhysical illness and lifestyle risk factors in people with their first presentation of psychosis
Samele, C., Patel, M. X., Boydell, J. E., Leese, M., Wessely, S. C., & Murray, R. M. (2006) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-006-0135-2 · Cited by 76 · see citing works
“Smoking is likely to aggravate existing respiratory conditions, and a recent study has shown, despite earlier reports to the contrary, that patients with schizophrenia are at increased risk of lung cancer [26].”
The prevalence of undiagnosed metabolic abnormalities in people with serious mental illness
Holt, R., Abdelrahman, T., Hirsch, M., et al. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109102788 · Cited by 76 · see citing works
Management of smoking in people with psychiatric disorders
Ziedonis, D. M., & Williams, J. M. (2003) · Current Opinion in Psychiatry · doi:10.1097/01.yco.0000069086.26384.5f · Cited by 75 · see citing works
Schizophrenia as one extreme of a sexually selected fitness indicator
Shaner, A. L., Miller, G. F., & Mintz, J. (2003) · Schizophrenia Research · doi:10.1016/j.schres.2003.09.014 · Cited by 75 · see citing works
“However, only two studies have reported possible survival advantages in relatives (Carter and Watts, 1971; Lichtermann et al., 2001) and while some studies have found reproductive advantages (Avila et al., 2001) others have not (Haukka et al., 2003).”
Ruiz, J. S., García, J. B., Ruiloba, J. V., Ubago, J. G., & González, M. P. G.-P. (2008) · Actas Españolas de Psiquiatría · Cited by 74 · see citing works
Interventions for smoking cessation and reduction in individuals with schizophrenia
Tsoi, D. T.-Y., Porwal, M., & Webster, A. C. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007253.pub2 · Cited by 71 · see citing works
Risk for Cancer in Parents of Patients With Schizophrenia
Dalton, S. O., Laursen, T. M., Mellemkjær, L., Johansen, C., & Mortensen, P. B. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.5.903 · Cited by 69 · see citing works
“Dalton, 2002) might correspond to the Finnish findings of an increased risk of lung cancer in the relatively young Finnish cohort (16), although we could not make comparisons by age group or period.”
BackgroundResultInfluentialSchizophrenia: The Epidemiological Horizon
Jablensky, A. V., Kirkbride, J. B., & Jones, P. B. (2010) · Wiley eBooks · doi:10.1002/9781444327298.ch10 · Cited by 65 · see citing works
Biomarkers of oxidative stress in schizophrenic and control subjects
Young, J. A., McKinney, S. B., Ross, B. M., Wahle, K. W. J., & Boyle, S. P. (2007) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2006.11.003 · Cited by 66 · see citing works
“It has been reported in population-based studies [28,29] that in the absence of confounding factors such as smoking, age, socioeconomic status and alcohol, the risk for some types of cancer (e.”
BackgroundTabac et schizophrénie : aspects épidémiologiques et cliniques
Dervaux, A., & Laqueille, X. (2008) · L Encéphale · doi:10.1016/j.encep.2007.04.003 · Cited by 63 · see citing works
Dysfunction in the coagulation system and schizophrenia
Hoirisch-Clapauch, S., Amaral, O. B., Mezzasalma, M. A., Panizzutti, R., & Nardi, A. E. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.204 · Cited by 57 · see citing works
Prochaska, J. J., Fromont, S. C., Louie, A. K., Jacobs, M., & Hall, S. M. (2006) · Academic Psychiatry · doi:10.1176/appi.ap.30.5.372 · Cited by 55 · see citing works
Schizophrenia and Cancer: In 2010 Do We Understand the Connection?
Bushe, C., & Hodgson, R. E. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005501203 · Cited by 55 · see citing works
“These data contrast with previous data that tend to report no difference.(8,30,35) However, the age of the Goldacre et al(8) cohort was young in terms of cancer incidence, with a modal age group of 25 to 29 years and an average follow-up period of 12.”
ResultCrespi, B. J. (2011) · Autism Research · doi:10.1002/aur.208 · Cited by 54 · see citing works
Osborn, D., Limburg, H., Walters, K. R., Petersen, I., King, M., Green, J., Watson, J. R., & Nazareth, I. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.11.009 · Cited by 54 · see citing works
“Others have reported increased cancer rates (Lichtermann et al., 2001).”
Ishikawa, H., Yasunaga, H., Matsui, H., Fushimi, K., & Kawakami, N. (2016) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.156265 · Cited by 53 · see citing works
Association between schizophrenia and genetic variation in DCC: a case–control study
Grant, A., Fathalli, F., Rouleau, G., Joober, R., & Flores, C. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.02.023 · Cited by 53 · see citing works
Mortality in first-contact psychosis patients in the UK: a cohort study
Dutta, R., Murray, R. M., Allardyce, J., Jones, P. B., & Boydell, J. E. (2012) · Psychological Medicine · doi:10.1017/s0033291711002807 · Cited by 53 · see citing works
Cancer in patients with schizophrenia: W hat is the next step?
Chou, F. H., Tsai, K., Wu, H., & Shen, S. (2016) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12420 · Cited by 53 · see citing works
“Lichtermann et al.(21) 2001 Finland A cohort of 26 996 individuals born between 1940 and”
BackgroundResultInfluentialHigher mortality and years of potential life lost of suicide in patients with schizophrenia
Ko, Y. S., Tsai, H.-C., Chi, M. H., Su, C., Lee, I. H., Chen, P. S., Chen, K. C., & Yang, Y. K. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.09.038 · Cited by 54 · see citing works
Pettersson, D. R., Gissler, M., Hällgren, J., Ösby, U., Westman, J., & Bobo, W. V. (2020) · Epidemiology and Psychiatric Sciences · doi:10.1017/s204579602000044x · Cited by 52 · see citing works
Weinberger, A. H., Sacco, K. A., Creeden, C. L., Vessicchio, J. C., Jatlow, P. I., & George, T. P. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.12.007 · Cited by 50 · see citing works
“Consequently, these patients experience earlier morbidity and mortality (Lichtermann et al., 2001), and reduced quality of life as a result of their recalcitrant smoking behavior (Dalack et al., 1998;Ziedonis et al., 2003).”
BackgroundThe physical health of the seriously mentally ill: an overview of the literature
Collins, E., Tranter, S., & Irvine, F. E. (2011) · Journal of Psychiatric and Mental Health Nursing · doi:10.1111/j.1365-2850.2011.01831.x · Cited by 49 · see citing works
Deaths from natural causes in people with mental illness: A cohort study
Hiroeh, U., Kapur, N., Webb, R. T., Dunn, G., Mortensen, P. B., & Appleby, L. (2008) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2007.09.008 · Cited by 49 · see citing works
“The protective effect may also be associated with the genes that code for schizophrenia [31], particularly with respect to lung cancer [32].”
BackgroundProchaska, J. J., Fromont, S. C., Leek, D., Hudmon, K. S., Louie, A. K., Jacobs, M., & Hall, S. M. (2008) · Academic Psychiatry · doi:10.1176/appi.ap.32.6.484 · Cited by 48 · see citing works
Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients
Park, J. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(03)00155-5 · Cited by 48 · see citing works
Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter
Asada, M., Ebihara, S., Numachi, Y., Okazaki, T., Yamanda, S., Ikeda, K., Yasuda, H., Sora, I., & Arai, H. (2008) · International Journal of Cancer · doi:10.1002/ijc.23562 · Cited by 47 · see citing works
“The risk of cancer among patients with schizophrenia has been discussed.(1,2) The majority of studies in the last decade suggested that patients with schizophrenia are protected against cancer in general, despite increased smoking(3,4) and drinking habits in this population.”
BackgroundEvaluation of the CHOICES Program of Peer-to-Peer Tobacco Education and Advocacy
Williams, J. M., Dwyer, M., Verna, M., Zimmermann, M. H., Gandhi, K. K., Galazyn, M., Szkodny, N., Molnar, M., Kley, R., & Steinberg, M. L. (2010) · Community Mental Health Journal · doi:10.1007/s10597-010-9310-8 · Cited by 46 · see citing works
“Smokers with psychiatric disorders have an increased risk for tobacco caused medical illnesses, and evidence of more than 20 years of life lost, compared to the general population (Brown et al. 2000; Lichtermann et al. 2001; Miller et al. 2006; NASMHPD 2006).”
BackgroundJablensky, A. V., & Lawrence, D. M. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.6.579 · Cited by 45 · see citing works
AhnAllen, C. G., Nestor, P. G., Shenton, M. E., McCarley, R. W., & Niznikiewicz, M. A. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.07.030 · Cited by 44 · see citing works
“Smokers with schizophrenia have elevated rates of lung cancer (Lichtermann et al., 2001), cardiovascular disease (Osby et al., 2000), tardive dyskinesia (Chong et al., 2003) and polydipsia (de Leon et Address reprint requests to: Christopher G. AhnAllen, Ph.D., Center for Alcohol and Addictions…”
BackgroundPhysical Illness and Schizophrenia
Leucht, S., Burkard, T., Henderson, J., Maj, M., & Sartorius, N. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511543951 · Cited by 45 · see citing works
Burdick, K. E., DeRosse, P., Kane, J. M., Lencz, T., & Malhotra, A. K. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09050615 · Cited by 43 · see citing works
Moss, T. G., Weinberger, A. H., Vessicchio, J. C., Mancuso, V., Cushing, S. J., Pett, M., Kitchen, K., Selby, P. L., & George, T. P. (2010) · American Journal on Addictions · doi:10.1111/j.1521-0391.2010.00051.x · Cited by 40 · see citing works
Lim, Y. J., Kim, J., Song, J. Y., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.10.055 · Cited by 41 · see citing works
- Authors
- Lichtermann, D., Ekelund, J., Pukkala, E., Tanskanen, A., & Lönnqvist, J.
- Affiliations
- University of Bonn (DE)
- Corresponding author
- Lichtermann, Dirk
- ORCID
- Pukkala, Eero
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2001-06-01
- Volume
- 58
- Issue
- 6
- Pages
- 573
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W11386986
- Cited by
- 292
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 10 · 2015: 9 · 2014: 13 · 2013: 17 · 2012: 16
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- 英文学評論
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, cancer incidence, lung cancer, pharyngeal cancer, family history (medicine), siblings, parents, genetic risk factors, smoking, alcohol consumption, shared risk factors
- MeSH terms
- Alcohol Drinking, Family, Female, Finland, Follow-Up Studies, Humans, Lung Neoplasms, Male, Neoplasms, Registries, Risk, Risk Factors, Risk-Taking, Schizophrenia, Smoking, Comorbidity, Incidence, Confidence Intervals, Genetic Predisposition to Disease
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