Journal ArticleDOI
Genetic Polymorphisms in DNA Repair Genes XRCC4 and XRCC5 and Aflatoxin B1–related Hepatocellular Carcinoma
Xi-Dai Long,Dong Zhao,Chao Wang,Xiao-Ying Huang,Jin-Guang Yao,Yun Ma,Zhong-Hua Wei,Min Liu,Li-Xiao Zeng,Xiao-Qiang Mo,Jianjun Zhang,Feng Xue,Bo Zhai,Qiang Xia +13 more
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TLDR
XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure and modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure.Abstract:
BACKGROUND Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and may play an important role in carcinogenesis. We investigated the role of genetic polymorphisms at XRCC4 codon 247 (rs3734091, XRCC4P) and XRCC5 codon 180 (rs80309960, XRCC5P) in liver cancer (hepatocellular carcinoma) caused by aflatoxin B1 (AFB1). METHODS A hospital-based case-control study, including 1499 liver cancer cases and 2045 controls without any liver disease, was conducted in a high aflatoxin exposure area in the Guangxi region of China to assess the relationship between these two polymorphisms and aflatoxin-related liver cancer risk and prognosis. Genotypes, mRNA levels, and the hot-spot mutation of TP53 gene (TP53M) related to AFB1 exposure was tested using TaqMan-PCR technique. XRCC4 protein level was analyzed by immunohistochemistry. RESULTS For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased liver cancer risk (odds ratio [OR] = 1.35 and 2.02, respectively). Significant interactive effects between risk genotypes (OR > 1) and aflatoxin exposure status were also observed in the joint effects analysis. Moreover, this polymorphism was associated not only with lower XRCC4 expression levels but also with higher AFB1-DNA adduct levels and increasing TP53M and portal vein tumor risk. Additionally, XRCC4P modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure. CONCLUSION XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure.read more
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The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients.
TL;DR: Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms and for early stage diagnosis in malignancies.
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Risk assessment of aflatoxins in food
Dieter Schrenk,Margherita Bignami,Laurent Bodin,James K. Chipman,Jesús del Mazo,Bettina Grasl-Kraupp,Christer Hogstrand,Laurentius Hoogenboom,Jean-Charles Leblanc,Carlo Nebbia,Elsa Nielsen,Evangelia E. Ntzani,Annette Petersen,Salomon Sand,Tanja Schwerdtle,Christiane Vleminckx,Doris Marko,Isabelle P. Oswald,Aldert H. Piersma,Michael Routledge,Josef Rudolf Schlatter,Katleen Baert,Petra Gergelova,Heather M. Wallace +23 more
TL;DR: The estimated cancer risks in humans following exposure to AFB1 and AFM1 are in‐line with the conclusion drawn from the MOEs, and the conclusions also apply to the combined exposure to all five aflatoxins.
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Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action.
TL;DR: This study reviews the most recent advances in the field of the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.
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The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer
Brock J. Sishc,Anthony J. Davis +1 more
TL;DR: NHEJ’s role as both a guardian and a disruptor of the genome is examined and how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics is explained.
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Mode of action-based risk assessment of genotoxic carcinogens
Andrea Hartwig,Michael Arand,Bernd Epe,Sabine Guth,Gunnar Jahnke,Alfonso Lampen,Hans Jörg Martus,Bernhard H. Monien,Ivonne M.C.M. Rietjens,Simone Schmitz-Spanke,G. Schriever‐Schwemmer,Pablo Steinberg,Gerhard Eisenbrand +12 more
TL;DR: An updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches.
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A Critical Role for DNA End-Joining Proteins in Both Lymphogenesis and Neurogenesis
Yijie Gao,Yi Sun,Karen M. Frank,Pieter Dikkes,Yuko Fujiwara,Katherine J. Seidl,JoAnn Sekiguchi,Gary Rathbun,Wojciech Swat,Jiyang Wang,Roderick T. Bronson,Barbara A. Malynn,Margaret Bryans,Chengming Zhu,Jayanta Chaudhuri,Laurie Davidson,Roger Ferrini,Thomas D. Stamato,Stuart H. Orkin,Michael E. Greenberg,Frederick W. Alt +20 more
TL;DR: These findings demonstrate that differentiating lymphocytes and neurons strictly require the XRCC4 and DNA ligase IV end-joining proteins and point to the general stage of neuronal development in which these proteins are necessary.
Journal ArticleDOI
Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development
Yijie Gao,David O. Ferguson,David O. Ferguson,Wei Xie,John P. Manis,JoAnn Sekiguchi,Karen M. Frank,Jayanta Chaudhuri,James W. Horner,Ronald A. DePinho,Frederick W. Alt +10 more
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