| Background:Chemotherapy-related fatigue(CRF)is one of the most common and most painful symptoms during chemotherapy treatment.Even after complete treatment,CRF will last for several years in the living patients.CRF is a kind of cancerous fatigue.The main clinical manifestations are depression,fatigue,lack of interest,cognitive decline,low quality of sleep,and influencing work and life of patients seriously.The degree of fatigue has nothing to do with the usual life activity,and CRF can’t relieve after a rest and sleep.A large number of studies have reported that the incidence of CRF has reached 75%to 100%.Many patients couldn’t stand CRF in the treatment,and had to give up the treatments.But little literature concerning colorectal cancer CRF can be found,and thus the analysis of the population at high risk susceptible to colorectal cancer CRF is of great significance for early prevention,early detection,early intervention in colorectal cancer CRF,and has clinical application prospects.But at present,little about colorectal cancer CRF is known.Serotonin(5-hydroxytrypt-amine,5-HT)activity is an important mechanism of CRF,and serotonin activity is regulated by the serotonin transporter promoter polymorphism(5-HTTLPR).So we speculated that 5-HTTLPR may be of great significance in the occurrence of colorectal cancer CRF.5-HTTLPR is one of the most studied gene polymorphism associated with emotion.Individuals with short type 5-HTTLPR gene are more likely to suffer from negative emotions,and CRF may cause fatigue,tiredness,depression and other negative emotions.So we speculated that 5-HTTLPR may be of great significance in the occurrence of colorectal cancer CRF from another angle.At the same time,there are more clinical data which report that 5-HTTLPR is related to irritable bowel syndrome.In recent years,several studies have reported the irritable bowel syndrome is associated with colorectal cancer,pancreatic cancer,kidney,liver and biliary malignancy,which shows the intestinal disease and tumor progression may be associated with 5-HTTLPR.But up to now,there have been few reports and studies about the correlations between 5-HTTLPR gene polymorphism and CRF,clinicopathological factors and prognosis of colorectal cancer.Objective:Through the analysis of the associations between 5-HTTLPR-gene polymorphisms and CRF,clinicopathological factors and prognosis of colorectal cancer,to further explore the epidemiological characteristics of colorectal cancer CRF,to provide a relatively reliable biomarkers for colorectal cancer CRF and prognosis,to investigate the significance of 5-HTTLPR in colorectal cancer progression and prognosis,to better guide the clinical individualized chemotherapy regimens.Methods:1.The required colorectal cancer patients according to the entry criteria were enrolled and the peripheral blood sample was collected.DNA of the patients was extracted and collected in the specimen bank.2.Common PCR amplification of 5-HTTLPR,and 5-HTTLPR genotypes were analyzed by agarose gel electrophoresis with different length of amplification.3.The patients were followed up by telephone and outpatient examination to record the data of postoperative recurrence,metastasis and survival,and the clinicopathological data of the enrolled patients were collected from the electronic medical record system.4.The independent risk of 5-HTTLPR for colorectal cancer CRF was analyzed by Multivariate Logistic regression model.The associations of 5-HTTLPR and the clinicopathologic factors were analyzed by chi-square test.The independent effect of 5-HTTLPR on survival of colorectal cancer was analyzed by Multivariate Cox model.Results:1.The group selected into the group conforms to the law of Hardy-Weinberg equilibrium(HWE).2.Chi-square test showed that chemotherapy-related fatigue was associated with 5-HTTLPR genotype(P = 0.025).Unconditional logistic regression model showed that patients with genotype SS genotype had a significantly higher risk of moderate to severe chemotherapy-related fatigue(OR = 8.225,95%Cl:1.694 to 39.927,P =0.009)than LL genotype.3.Single factor analysis showed that lymph node metastasis was associated with 5-HTTLPR gene polymorphism[LL and LS genotypes of lymph node metastasis rate was 29.4%(15/71),SS genotypes of lymph node metastasis rate was 70.36%(36/90),χ2=6.532,P = 0.011).The 3 years OS of the patients in our study was whole ground of was 71%,and the 5 years OS was 63%.Multivariate analysis showed that the SS genotype was just an independent risk factor affecting the overall survival of postoperative chemotherapy patients after colorectal cancer(HR=1.933,95%CI:1.090～3.428,P=0.024).Conclusion:SS genotype of 5-HTTLPR is an independent risk factor for moderate to severe CRF in colorectal cancer.Mental condition should be paid more attention to in those with SS genotype.SS genotype of 5-HTTLPR has more risk of lymph node metastasis and the worse prognosis. |
PDF Full Text Request