As a DNA repair protein, Flap endonuclease 1 (FEN1) plays crucial parts in preventing carcinogenesis. Two functional germ line variants (-69G > A and 4150G > T) in the FEN1 gene have been associated with DNA damage levels in coke oven workers and lung cancer risk in general populations. However, the role of these genetic variants on gastrointestinal cancer susceptibility is unknown. Therefore, we evaluated the association between these polymorphisms and gastrointestinal cancer risk in two independent case-control cohorts consisted of a total of 1850 gastrointestinal cancer (hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer) patients and 2222 healthy controls. The impact of these variations on FEN1 expression was also examined using liver, esophagus, stomach and colon normal tissues. It was found that the FEN1 -69GG genotypes were significantly correlated to increased risk for developing gastrointestinal cancer compared with the -69AA genotype in both cohorts [Jinan cohort: odds ratios (OR) = 2.14, 95% confidence interval (CI) = 1.47-2.80, P = 1.0 × 10(-)(6); Huaian cohort: OR = 1.93, 95% CI = 1.37-2.50, P = 0.5 × 10(-6)]. Similar results were observed for 4150G > T polymorphism. In the combined meta-analyses, OR for -69GG or 4150GG genotype was 2.02 (95% CI = 1.59-2.45) or 1.86 (95% CI = 1.45-2.28) compared with -69AA or 4150TT genotype. In vivo FEN1 messenger RNA expression analyses showed that the -69G or 4150G allele carriers had ∼2-fold decreased FEN1 expression in gastrointestinal tissues compared with -69A or 4150T carriers, indicating that lower FEN1 expression may lead to higher risk for malignant transformation of gastrointestinal cells. Our results highlight FEN1 as an important gene in human gastrointestinal oncogenesis and genetic polymorphisms in FEN1 confer susceptibility to gastrointestinal cancers.
Background: As a neutral lipid and prominent component of the Western diet, cholesterol levels might be a risk factor for prostate cancer. However, current evidence has been inconsistent. This meta-analysis aimed to evaluate the association between blood cholesterol levels and the risk of prostate cancer.Methods: An extensive search was performed in MEDLINE and EMBASE for prospective studies that have reported the association between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) levels in blood and risk of prostate cancer. Random-effects models were used to summarize the study-specific results.Results: Fourteen studies were included in this meta-analysis. In the meta-analysis, the summarized risk ratios (RR) for the highest to lowest cholesterol levels were as follows: 1.05 [95%
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.