5-HTTLPR and use of antidepressants after colorectal cancer including a meta-analysis of 5-HTTLPR and depression after cancer.
The serotonin-transporter-linked polymorphic region (5-HTTLPR) is one of the most extensively investigated candidates to be involved in gene-environment interaction associated with depression. Nevertheless, the interaction remains controversial. In an original study, we tested the hypothesis that risk for use of antidepressants following a diagnosis of colorectal cancer is associated with bi- and triallelic genotypes of 5-HTTLPR. In addition, in an inclusive meta-analysis, we tested the hypothesis that depression following a diagnosis of cancer is associated with biallelic 5-HTTLPR genotype. We created an exposed-only cohort of 849 colorectal cancer patients from the Danish Diet, Cancer and Health cohort study. The hypothesized association was investigated with Cox regression models and competing risk analyses. Five studies comprising a total of 1484 cancer patients were included in the meta-analysis. Nationwide registries provided information on dates of diagnosis of colorectal cancer and use of antidepressants. Unadjusted odds ratios of depression according to the biallelic 5-HTTLPR genotype were included in the meta-analysis. 5-HTTLPR genotypes were not associated with use of antidepressants after colorectal cancer. Estimated hazard ratios ranged 0.92-1.08, and we observed no statistically significant associations across biallelic and triallelic genotypes in crude as well as adjusted models. The meta-analysis showed no statistically significant associations of 5-HTTLPR biallelic genotype with depression after cancer. Our findings in an original study and a meta-analysis do not support the hypothesis of an association between the 5-HTTLPR genotype and depression after cancer.
Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark.|Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
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Suppli
Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
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Bukh
Department of Psychology and Neuroscience, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|Department of Psychiatry and Behavioral Sciences, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, King's College London, London, UK.
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Moffitt
Department of Psychology and Neuroscience, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|Department of Psychiatry and Behavioral Sciences, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, King's College London, London, UK.
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Caspi
Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark.|Department of Oncology, Finsencentret, Rigshospitalet, Copenhagen, Denmark.
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Johansen
Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark.
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Albieri
Unit of Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
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Tjønneland
Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
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Kessing
Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark.
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Dalton
D000928:Antidepressive Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000150:complications* / Q000523:psychology*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D000928:Antidepressive Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins