Flap endonuclease 1 (FEN1) is a key enzyme in maintaining genomic stability and protecting against carcinogenesis. This study investigated whether functional variations in FEN1 gene are associated with DNA damage and lung cancer risk. Thirty DNA samples were sequenced to identify variants and function of the variants was examined by a set of biochemical assays. DNA damage levels were detected by comet assays in a cohort of 303 coke-oven workers and 297 controls. The association with lung cancer risk was examined in two independent case-control panels consisted of a total 1,840 lung cancer patients and 1,958 controls. We identified two single nucleotide polymorphisms (SNPs) located in the FEN1 promoter c.-69G>A (rs174538:G>A) and 3'-untranslational region c.4150G>T (rs4246215:G>T) that were associated with reduced FEN1 expression. Among coke-oven workers, DNA damage levels were significantly higher in the -69GG or GA carriers compared with the -69AA carriers. The -69GG or 4150GG carriers had a significantly increased risk for developing lung cancer compared with the -69AA or 4150TT carriers. These results highlight FEN1 as an important gene in human carcinogenesis and genetic polymorphisms in FEN1 confer susceptibility to lung cancer.
Polylysine is an important class of polyamino acids with a broad spectrum of applications in biomedical research and development. It can be divided into two classes, α-polylysine and ε-polylysine, the former is synthesized by artificial chemical synthesis and has limited applications due to its high toxicity, and the latter is produced by microbial synthesis as a class of natural polymers and is widely used in various food, medicinal, and electronics products. Another major class of synthetic polymers is dendrimers (after linear, cross-linked, and branched polymers). Dendrigraft poly-L-lysine (DGL) has the favorable properties of polylysine and dendrimers, with a broad spectrum of applications in drug discovery and development, including drug delivery, gene carriers, diagnostic imaging, diagnostics, biosensors, and special cancer therapies (such as boron neutron capture therapy and photodynamic therapy). As there are still some problems with the development of DGL, further research is warranted for its broad applications.
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