| Live cancer is the fifth most frequent malignancy and the second leading causeof cancer death throughout the world. Half of these cases are estimated in China.Hepatocellular carcinoma (HCC) represents the major histological type andaccounted for about90%of primary liver cancers. Although much progress intreatment of HCC has been obtained in the past two decades, the5-year survivalrates of HCC patient still remain to be less than10%.Transcatheter arterial chemoembolization (TACE) is one of the therapiesrecommended as first-line therapy for unresectable HCC patients. It has beendemonstrated that TACE signigicantly improves the overall-survival ofunresectable HCC patients. Treatment outcomes of TACE are affected bymultiple baseline clinical factors and vary significantly among HCC patients.Thus, identification of those patients who can benefit from TACE will greatlyimprove patients’ survival. However, to date, the major problem for clinicians to fight against HCC is the lack of effective and specific biomarkers for thevariegated treatments.In recent years, All kinds of genetic susceptibility factor and environmentalfactors takes the key point in HCC researches, including the establishment of theearly screening technology and risk assessment model for HCC.also theprediction of tumor tumorigenesis, progression and metastasis. Single NucleotidePolymorphisms(SNPs) as the third generation of molecular markers, The mostcommon kind of form of hereditary variation, can reflect patients’geneticbackground quite accurately and simple detection.However,It’s importantfunction not widely used in in clinic practice. emerging evidence indicates thatSNPs were significantly associated with Tumor angiogenesis, development andmetastasis.by far the SNPs which significantly related with the prognosis of HCCpatients are still very few. and most of them haven’t been verified in Asianpopulation,especially in Han population.So find SNP sites for the prognosisassessment of HCC in Han population to be solved immediatelyCircadian rhythm is a roughly24-hour cycle in the behavioral, physiologicaland biochemical processes, such as temperature, sleep, and energy metabolism.The mammalian circadian clock consists of a principal central pacemaker andsubsidiary intrinsic clocks. The molecular mechanisms of circadian oscillationare based on positive/negative transcriptional-translational feedback loopgenerated by at least ten core circadian genes. Recently, emerging evidenceindicates that the disruption of circadian rhythms significantly increases theincidence of many malignancies. Previous studies have revealed that circadiangenes play important roles in cell proliferation, apoptosis, cell cycle control,DNA damage response and treatment response of chemotherapy agents incancers. Aims: we hypothesized that the polymorphisms in circadian genes may beassociated with prognosis of hepatocellular carcinoma (HCC) patients treatedwith transcatheterarterial chemoembolization (TACE).Methods: multiple functional SNPs in circadian genes were genotyped usingSequenom iPLEX genotyping method in337HCC patients treated with TACEand analyzed for associations with overall survival.Results:○1. Our data showed that one SNP rs2640908in PER3gene wassignificantly associated with overall survival of HCC patients (P=0.027).Patients carrying at least one variant allele of rs2640908(WV+VV) had asignificantly decreased risk of death (HR,0.71;95%CI,0.53-0.90), whencompared with those carrying homozygous wild-type alleles (WW). analysesshowed a significantly longer median survival time (MST) in patients with WV+VV genotypes of SNP rs2640908than those with WW genotype (11.6months vs.8.1months; log rank P=0.030). In addition, we also observed that there was asignificant difference on the genotype distribution of SNP rs2640908in patientswith and without PVT (P=0.041).○2. We analyzed the effect of SNP rs2292910in CRY2gene on overall survival in unresectable HCC patients stratified bydemographic and clinicopathological characteristics. the significant decreaseddeath risk conferred by SNP rs2292910was observed in older patients and inthose with tumor size﹤5cm patients. Kaplan-Meier analyses and Log rank testindicated the same results.Conclusion: Our results for the first time suggest that SNP rs2640908in PER3gene is significantly associated with overall survival of HCC patients, also ourdate suggest that SNP rs2292910in CRY2may be used as an independentprognostic marker for older age and smaller tumor size HCC patients treated withTACE. |
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