Utilization of 5HTT gene polymorphism as a prognostic indicator in cancer , STDF GRANT 225/2009
Cancer patients with curable/controllable disease who deteriorate without clinically detectable physical cause have led researchers to investigate the relation between depression and cancer progression. Studies showed an association between depression and cancer outcomes as decreased compliance, decreased desire for life-sustaining treatment and increased mortality.
Lab studies show that neurotransmitters are capable of altering immune function whereas immune-derived mediators regulate neuroendocrine and autonomic outflow from the brain. Host cellular defenses against cancer involve immune mediated mechanisms that can be influenced by neurotransmitter activity.
Caspi et al demonstrated that polymorphism of the 5-HTT gene explains why some individuals develop psychological morbidities on exposure to stressful life events while others exposed to the same conditions don't. This offers a screening criterion for identifying patients at risk for psychological morbidity that might be detrimental to their treatment outcome and may be used as a prognostic indicator in which case, starting anti-cancer treatment of this group of patients with concurrent psychological intervention may improve their treatment outcomes. AIM: To study the role of 5HTT gene as a prognostic indicator in cancer and its utilization for clinical selection of patients for concurrent psychotherapy with anticancer treatment.
A two study research program: Study I is a longitudinal observational study in which cancer outcomes are compared in two independent cohorts of cancer patients grouped by 5HTT genotype (patients with two long alleles versus those with at least one short allele). In Study II, patients with at least one short allele will be randomized into either an intervention arm receiving anticancer treatment accompanied by supportive psychiatric care program or control arm receiving standard care (anticancer treatment without psychotherapy).
Primary outcome measure is progression free survival. Secondary outcomes are response to treatment, functional and psychological status of the patient as expressed by Quality of Life (QOL) measurement using FACT-G questionnaire and Mental Adjustment to Cancer (MAC) questionnaire, and overall survival.