Risk of malignancy in patients with schizophrenia or bipolar disorder: nested case-control study.

CONTEXT There is conflicting evidence on whether people with schizophrenia have a different risk of cancer from that of the general population. OBJECTIVE To determine the risk of 6 common cancers in patients with schizophrenia or bipolar disorder. DESIGN Population-based, nested, case-control study. SETTING A total of 454 practices contributing to the QRESEARCH general practice database. PARTICIPANTS We analyzed 40,441 incident cases of 6 cancers (breast, colon, rectal, gastroesophageal, prostate, and respiratory) and up to 5 controls per case matched by single year of age, sex, general practice, and calendar time. MAIN OUTCOME MEASURES Odds ratios (ORs) for cancer risk associated with schizophrenia and bipolar disorder, adjusting for smoking, body mass index, socioeconomic status, comorbidities, and prescribed medications, including antipsychotics. RESULTS For breast cancer, we identified 10,535/50,074 cases/controls; colon cancer, 5108/24,458; rectal cancer, 3248/15,552; gastroesophageal cancer, 3854/18,477; prostate cancer, 10,190/48,748; and respiratory cancer, 7506/35,981. After adjustment, patients with schizophrenia had a 190% increased colon cancer risk (adjusted OR, 2.90; 95% confidence interval [CI], 1.85-4.57), a marginal increased breast cancer risk (adjusted OR, 1.52; 95% CI, 1.10-2.11), and a 47% decreased respiratory cancer risk (adjusted OR, 0.53, 95% CI, 0.34-0.85). Patients with schizophrenia taking antipsychotics had a 308% increased colon cancer risk (adjusted OR, 4.08; 95% CI, 2.43-6.84). Patients with bipolar disorder had cancer risks similar to patients with neither condition after adjustment. CONCLUSIONS Patients with schizophrenia have a significantly higher risk of colon cancer and a lower risk of respiratory cancer compared with patients without schizophrenia after adjustment for confounders. In contrast, the risks of cancer in patients with and without bipolar disorder are similar, suggesting that residual confounding is unlikely to explain the findings. The increased risk of colon cancer is particularly marked in patients with schizophrenia who take antipsychotic medications.

[1]  D. Jeste,et al.  Medical comorbidity in schizophrenia. , 1996, Schizophrenia bulletin.

[2]  U. Halbreich,et al.  Are chronic psychiatric patients at increased risk for developing breast cancer? , 1996, The American journal of psychiatry.

[3]  Brian L. Smith,et al.  Physical Health of the Long-Term Mentally Ill in the Community , 1989, British Journal of Psychiatry.

[4]  John M Davis,et al.  Physical health monitoring of patients with schizophrenia. , 2004, The American journal of psychiatry.

[5]  S. Marder,et al.  Novel antipsychotics: comparison of weight gain liabilities. , 1999, The Journal of clinical psychiatry.

[6]  B. Barraclough,et al.  Causes of the excess mortality of schizophrenia. , 2000, The British journal of psychiatry : the journal of mental science.

[7]  L. Dixon,et al.  Prevalence and correlates of diabetes in national schizophrenia samples. , 2000, Schizophrenia bulletin.

[8]  Valerie Beral,et al.  Breast cancer and hormone-replacement therapy in the Million Women Study , 2003, The Lancet.

[9]  V. Lehtinen,et al.  Mental disorders and cause-specific mortality , 2001, British Journal of Psychiatry.

[10]  R. McCreadie,et al.  Use of drugs, alcohol and tobacco by people with schizophrenia: case–control study , 2002, British Journal of Psychiatry.

[11]  H. Adami,et al.  Use of oral contraceptives and breast cancer risk: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[12]  H. Sørensen,et al.  Cancer risk among users of neuroleptic medication: a population-based cohort study , 2006, British Journal of Cancer.

[13]  Effect of combinations of drugs on all cause mortality in patients with ischaemic heart disease: nested case-control analysis , 2005, BMJ : British Medical Journal.

[14]  M. Singer,et al.  BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults , 2004, International Journal of Obesity.

[15]  I. Levav,et al.  Cancer in schizophrenia: is the risk higher or lower? , 2005, Schizophrenia Research.

[16]  S. Kono,et al.  Mortality in psychiatric patients, with a specific focus on cancer mortality associated with schizophrenia. , 1995, International journal of epidemiology.

[17]  M. Goldacre,et al.  Schizophrenia and cancer: an epidemiological study. , 2005, The British journal of psychiatry : the journal of mental science.

[18]  S. Catts,et al.  Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene? , 2000, Schizophrenia Research.

[19]  J. Hippisley-Cox,et al.  A comparison of research general practices and their patients with other practices--a cross-sectional survey in Trent. , 2002, The British journal of general practice : the journal of the Royal College of General Practitioners.

[20]  J. Hippisley-Cox,et al.  Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis , 2005, BMJ : British Medical Journal.

[21]  J. A. Carrillo,et al.  Are antipsychotic drugs potentially chemopreventive agents for cancer? , 1999, European Journal of Clinical Pharmacology.

[22]  J. Klenk,et al.  Obesity and incidence of cancer: a large cohort study of over 145 000 adults in Austria , 2005, British Journal of Cancer.

[23]  A. Tanskanen,et al.  Incidence of cancer among persons with schizophrenia and their relatives. , 2001, Archives of general psychiatry.

[24]  C. la Vecchia,et al.  Hormone replacement therapy and risk of colon and rectal cancer. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[25]  H. Jick,et al.  Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis , 2000, BMJ : British Medical Journal.

[26]  Christoffer Johansen,et al.  Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969–1993 , 2005, Schizophrenia Research.

[27]  Mark Garton,et al.  Breast cancer and hormone-replacement therapy: the Million Women Study , 2003, The Lancet.

[28]  L. Brown Epidemiology of alcohol-associated cancers. , 2005, Alcohol.

[29]  M. Cohen,et al.  The association between schizophrenia and cancer: a population-based mortality study , 2002, Schizophrenia Research.

[30]  A. Jablensky,et al.  Cancer Incidence of Schizophrenic Patients Results of Record Linkage Studies in Three Countries , 1992, British Journal of Psychiatry.

[31]  Preben Bo Mortensen,et al.  The occurence of cancer in first admitted schizophrenic patients , 1994, Schizophrenia Research.

[32]  R. McCreadie,et al.  Diet, smoking and cardiovascular risk in people with schizophrenia: descriptive study. , 2003, The British journal of psychiatry : the journal of mental science.

[33]  P. Mortensen,et al.  Neuroleptic medication and reduced risk of prostate cancer in schizophrenic patients , 1992, Acta psychiatrica Scandinavica.

[34]  H Jick,et al.  Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. , 1991, BMJ.

[35]  Mike Pringle,et al.  Methodology for Assessing the Usefulness of General Practice Data for Research in One Research Network , 2004, Health Informatics J..

[36]  A. Jablensky,et al.  Excess cancer mortality in Western Australian psychiatric patients due to higher case fatality rates , 2000, Acta psychiatrica Scandinavica.

[37]  A. Majeed Sources, uses, strengths and limitations of data collected in primary care in England. , 2004, Health statistics quarterly.

[38]  Carol Coupland,et al.  Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis , 2005, BMJ : British Medical Journal.

[39]  C. Johansen,et al.  Schizophrenia and the risk for breast cancer , 2003, Schizophrenia Research.

[40]  A. Achiron,et al.  Reduced cancer incidence among patients with schizophrenia , 2005, Cancer.

[41]  Edward Giovannucci,et al.  Modifiable risk factors for colon cancer. , 2002, Gastroenterology clinics of North America.

[42]  A Haines,et al.  Accuracy of diagnosis of psychosis on general practice computer system. , 1993, BMJ.

[43]  A. Leclerc,et al.  Social inequalities and cancer mortality in France, 1975–1990 , 2005, Cancer Causes & Control.

[44]  Galit Yovel,et al.  Higher Natural Killer Cell Activity in Schizophrenic Patients: The Impact of Serum Factors, Medication, and Smoking , 2000, Brain, Behavior, and Immunity.

[45]  L. Kahn,et al.  Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects , 2003, Psychoneuroendocrinology.