Effect of 5HTT gene polymorphism on immune response in cancer; a psychoneuro-immunology research program
In spite of the phenomenal progress of cancer medicine over the past few decades, oncologists continue to come across cancer patients who deteriorate inexplicably, without a plausible clinical explanation.
The clinical observation of psychological morbidity in these patients led researchers to inquire into the association between psychological morbidity and cancer progression.
The serotonin transporter gene was found to be a major determinant of psychological morbidity. Our previous research demonstrated an association between depression and various cancer outcomes, particularly in carriers of the short allele of the serotonin transporter gene.
Similarly, depression has been found to affect numerous immune processes.
Since host defenses against cancer are largely immune based, it is possible that depression-mediated immune dysregulation underlies the process of cancer progression in carriers of the short allele of the serotonin transposter gene.
To investigate the immune events that underly cancer progression in cancer patients with short/short genotype of the serotonin transporter gene as compared to other genotypes.
A prospective longitudinal study of three cohorts of cancer patients who represent the three genotypes of the serotonin transporter gene, where patients will be genotyped at study entry and tested at three monthly intervals for a panel of immune markers including natural killer cell cytotoxicity, blastogenic response to haemagglutinin, quantification of lymphocyte subsets using cell surface markers (CD25-CD4+ effector T cells, CD25+CD4+ regulatory Tcells, and CD4- antigen presenting cells), plasma concentrations of cytokines (IL-2, IL-6, IIL-12, Interferon INF-gamma and TNF-alpha).
Patients will be followed up for two years. These tests will be repeated at 3 month intervals from the time of recruitment. Comparison will be made on the basis of the panel of investigations at comparable time points among all three groups.
The primary outcome of the study is to detect a difference of, at least, 15% in each of the immunological parameters under investigation between the short allele carriers and the long/long genotype.
To enable the identification of patients in whom immune manipulation or immunotherapy may stop preventable disease progression.