Abstract
Prognosis in colorectal cancer patients is quite variable, even after adjustment for clinical parameters such as disease stage and microsatellite instability status. It is possible that the psychological distress experienced by patients, including anxiety and depression, may be correlated with poor prognosis. In the present study, we hypothesize that genetic variations within three genes biologically linked to the stress response, namely serotonin transporter (SLC6A4), brain-derived neurotrophic factor (BDNF), and arginine vasopressin receptor (AVPR1B) genes are associated with prognosis in colorectal cancer patients. We used a population-based cohort of 280 patients who were followed for up to 12.5 years after diagnosis. Our multivariate analysis showed that a tagSNP in the SLC6A4 gene (rs12150214) was a predictor of shorter overall survival (HR: 1.572, 95%CI: 1.142–2.164, p = 0.005) independent of stage, age, grade and MSI status. Additionally, a multivariate analysis using the combined genotypes of three polymorphisms in this gene demonstrated that the presence of any of the minor alleles at these polymorphic loci was an independent predictor of both shorter overall survival (HR: 1.631, 95%CI: 1.190–2.236, p = 0.002) and shorter disease specific survival (HR: 1.691, 95%CI: 1.138–2.512, p = 0.009). The 5-HTT protein coded by the SLC6A4 gene has also been implicated in inflammation. While our results remain to be replicated in other patient cohorts, we suggest that the genetic variations in the SLC6A4 gene contribute to poor survival in colorectal cancer patients.
Highlights
Colorectal cancer is a common disease with millions of new cases worldwide each year
We identified tagSNPs with a minor allele frequencies .10% in these genes using the genotype information for Caucasians posted in the HapMap database, phase I & II and using the pair-wise tagger function implemented in the Haploview program [17]
While well-established prognostic markers such as disease stage are used in prognostication, an inter-patient prognostic variability remains [3]
Summary
Colorectal cancer is a common disease with millions of new cases worldwide each year. Clinical outcomes are associated with disease stage, age, and comorbidities [3]. An important determinant of the emotional health and quality of life in cancer patients is the patients’ effectiveness of coping with the psychological distress caused by the cancer diagnosis and the undesirable consequences of treatment. In patients with advanced stage, especially in palliative care, coping with the prospect of death is a serious emotional burden. These challenges often surface as depression or anxiety in cancer patients, which are observed in up to 50% of cancer patients [4]. Some studies have suggested an association between distress coping effectiveness and survival in cancer patients [5,6], conflicting results have been reported [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
