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Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data.

ABSTRACT: Observational epidemiological studies have found an association between schizophrenia and breast cancer, but it is not known if the relationship is a causal one. We used summary statistics from very large genome-wide association studies of schizophrenia (n = 40675 cases and 64643 controls) and breast cancer (n = 122977 cases and 105974 controls) to investigate whether there is evidence that the association is partly due to shared genetic risk factors and whether there is evidence of a causal relationship. Using LD-score regression, we found that there is a small but significant genetic correlation (rG) between the 2 disorders (rG = 0.14, SE = 0.03, P = 4.75 × 10-8), indicating shared genetic risk factors. Using 142 genetic variants associated with schizophrenia as instrumental variables that are a proxy for having schizophrenia, we estimated a causal effect of schizophrenia on breast cancer on the observed scale as bxy = 0.032 (SE = 0.009, P = 2.3 × 10-4). A 1 SD increase in liability to schizophrenia increases risk of breast cancer 1.09-fold. In contrast, the estimated causal effect of breast cancer on schizophrenia from 191 instruments was not significantly different from zero (bxy = -0.005, SE = 0.012, P = .67). No evidence for pleiotropy was found and adjusting for the effects of smoking or parity did not alter the results. These results provide evidence that the previously observed association is due to schizophrenia causally increasing risk for breast cancer. Genetic variants may provide an avenue to elucidating the mechanism underpinning this relationship.

SUBMITTER: Byrne EM

PROVIDER: S-EPMC6811821 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data.

Byrne Enda M EM Ferreira Manuel A R MAR Xue Angli A Lindström Sara S Jiang Xia X Yang Jian J Easton Douglas F DF Wray Naomi R NR Chenevix-Trench Georgia G

Schizophrenia bulletin 20191001 6

Observational epidemiological studies have found an association between schizophrenia and breast cancer, but it is not known if the relationship is a causal one. We used summary statistics from very large genome-wide association studies of schizophrenia (n = 40675 cases and 64643 controls) and breast cancer (n = 122977 cases and 105974 controls) to investigate whether there is evidence that the association is partly due to shared genetic risk factors and whether there is evidence of a causal rel ...[more]

PMID: 30452727

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Project description:BackgroundThe effect of antipsychotics on breast cancer remains controversial.Materials and methodsEmbase, Scopus, PubMed, Web of Science, Cochrane Library, and Hebei Medical University Library were used for the literature search. Observational studies with original data for the effects of antipsychotics on breast cancer were used. Studies of bed quality, those with inadequate sample size, incomplete follow-up works, or studies that did not meet the criteria were excluded. Meta-analysis was performed using R version 4.1.2. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the proportion of breast cancer in different groups. To detect possible sources of heterogeneity, subgroup and meta-regression analyses were employed.ResultsPooled data from 11 relevant studies with 1,499,001 participants suggested that individuals exposed to antipsychotics were more likely to suffer from breast cancer than those who were not exposed (OR, 1.23; 95% CI, 1.04-1.47). No significant difference in breast cancer prevalence between the atypical and typical antipsychotic groups was found (OR, 1.23; 95% CI, 0.93-1.63). Prolactin (PRL)-increasing and PRL-sparing antipsychotics posed a similar risk of breast cancer (OR, 1.13; 95% CI, approximately 0.97-1.31). Furthermore, the use of antipsychotics is attributed to increased mortality in patients with breast cancer (OR, 1.54; 95% CI, 1.29-1.82). Those exposed to antipsychotics at the maximum dose were more likely to suffer from breast cancer than those exposed to the minimum dose.ConclusionsAntipsychotic exposure is an independent risk factor for breast cancer. No significant difference in the risk of breast cancer between typical and atypical antipsychotics was noted. Those exposed to antipsychotics at higher doses are more likely to suffer from breast cancer. Moreover, the use of antipsychotics is attributed to increased mortality in patients with breast cancer. PRL-increasing and PRL-sparing antipsychotics pose a similar risk of breast cancer.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022307624.

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Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data.

Publications

Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data.

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