Association Between Telomere Length And Colorectal Cancer Risk

Background: Colorectal cancer (CRC) is one of the most common cancers in the world,which is leading a very high incidence and mortality. In China, the incidence andmortality of CRC increased rapidly in the past decades, and CRC has been a seriousproblem for public health. The pathogenesis of CRC remains unclear, but it has beenknown as a result of complicated interaction between environmental factors and geneticfactors. Recent epidemiologic evidence indicated an association between telomere lengthand CRC risk, although the results have been conflicting.We conducted a case-control study to evaluate the association between telomerelength and CRC risk, using a few environmental factors as adjusting factors. Ameta-analysis was also performed to estimate the CRC risk associated with telomerelength and to evaluate potential between-study heterogeneity of identified studies.Methods:1. A case-control study was conducted, and a questionnaire was designed to collectthe main demographic characteristics and exposure information. T test and χ2test wereused to examine differences between cases and controls in distribution of the mainenvironmental factors. DNA of peripheral blood was extracted, and the relative telomerelength ratio (TSR) was measured by quantitative PCR (qPCR). Unconditional logisticregressions were used to calculate adjusted odds ratios (OR) with95%confidenceintervals (95%CI) as the indicator of association between telomere length and CRC risk.2. In the meta-analysis, the pooled ORs and95%CI were reported. Additionally, thequality of identified studies, publication bias and heterogeneity between the studies werecalculated. Results:1. The study included462cases and467controls. Drinking and CRC family historywas found to increase the risk of CRC, with ORs of2.54and1.80, respectively.The coefficients of variation (CV) of the telomere, single-gene, and TSR duplicateassays were all <5%, respectively. A significant association was observed betweenshorten telomere length and colorectal cancer risk (OR=1.38,95%CI=1.06-1.78,P=0.016), but not after the adjustment of age, gender, body mass index, CRC familyhistory, smoking and drinking. A U-shaped association was revealed when the data wasgrouped by quintiles, and the risks were increased with a shorter or longer telomerelength.2. The meta-analysis included6studies, with an average score of8.5. Litterpublication bias was detected by Begg’test. The pooled result showed an increased riskbetween shorten telomere length and CRC (OR=1.21,95%CI=1.01-1.42, P<0.05).Conclusions: Drinking, CRC family history and shorten telomere length are associatedwith increased risk of CRC, and a longer telomere length may increase the risk of CRC,too.