The Association Between Leukocyte Telomere Length And The Risk And Prognosis Of Gastric Cardia Adenocarcinoma

Background and purpose:In recent years,several studies have demonstrated that shortened telomeres were associated with the development of cancers,such as esophageal cancer,gastric cancer,and lung cancer.But it is still largely unclear whether leukocyte telomere length in peripheral blood contributes to predisposition of gastric cardia adenocarcinoma（GCA）.Our study evaluated the relationship between the relative telomere length（RTL）of leukocytes and the risk of GCA.Meanwhile,we also explored the role of RTL in predicting the prognosis of GCA.Methods:We conducted a case-control study consisting of 524 GCA patients with histologically confirmed GCA,and 510 matched controls.All GCA cases and controls included in this study are Chinese Han population.Telomere length was measured in genomic DNA of peripheral blood leukocytes by SYBR Green quantitative polymerase chain reaction（qPCR）protocol.RTL was analyzed as a categorial variable and was categorized into four groups according to its quartile distribution in controls.The logistic regression model was utilized to calculate the odds ratio（OR）and 95%confidence intervals（CI）in order to evaluate the association between RTL and GCA risk in each quartile.Overall survival（OS）was defined as the time from the date of diagnosis to the date of death.Kaplan–Meier method was used to calculate and analyze the median probabilities and 95%CIs of OS.Cox hazard regression analyses were used to calculate the hazard ratios（HRs）and their 95%CI.Results:The GCA patients had significantly overall shorter relative RTL（Mean±SD:1.10±0.54）when compared with the controls（1.24±0.58）.We first dichotomized RTL into the long telomere group and the short telomere group based on the median telomere length of controls.With an adjustment for age,sex,smoking status and drinking status,we found a significantly elevated GCA risk(OR=1.71,95%CI=1.31-2.24,P=9.05×10^-5)among patients with short RTL.Quartiles analyses of RTL showed that individuals with the shortest quartile of RTL performed a doubled GCA risk(OR=2.18,95%CI=1.47-3.22,P=9.90×10^-5)when compared with those with the highest quartile,indicating a significant dose-response relationship between telomere length shortening and increased GCA risk.We also found that telomere shortening and smoking have a significantly synergistic effect in intensifying risk of GCA and the group of smokers with short RTL had highest GCA risk,with the OR being 7.03(95%CI=4.55-10.86,P=1.43×10^-18).Furthermore,GCA patients with shortened RTL had a reduced OS compared with patients with long telomeres（median OS:21.2 vs.29.2 months,P=0.029）,implying that short RTL was significantly associated with poorer GCA prognosis（HR=1.40,95%CI=1.05-1.88,P=0.024）.Conclusions:In Chinese Han population,short RTL contributes to increased susceptibility of GCA and there is a significantly synergistic effect between short telomeres and smoking in elevating GCA risk.In addition,shorter RTL might indicate poorer prognosis for GCA patients.