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Genes and Environment

, 38:26

Lifestyle and cancer


Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species ROS and reactive nitrogen species RNS are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2’-deoxyguanosine 8-oxodG and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans IARC group 1, including bacterium Helicobacter pylori H. pylori, viruses hepatitis B virus HBV, hepatitis C virus HCV, human papillomavirus HPV and Epstein-Barr virus EBV and parasites Schistosoma haematobium SH and Opisthorchis viverrini OV. H. pylori, HBV-HCV, HPV, EBV, SH and OV are important risk factors for gastric cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, bladder cancer, and cholangiocarcinoma, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase iNOS expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3-4-positive stem cells in SH-associated bladder cancer tissues, and in Oct3-4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that nitrative and oxidative DNA damage in stem cells may play a key role in infection-related carcinogenesis via chronic inflammation.

Keywords8-OHdG 8-oxodG 8-nitroguanine Oxidative stress Inflammation Abbreviations8-oxodG8-oxo-7,8-dihydro-2’-deoxyguanosine


BMDCsBone marrow-derived cells

CagACytotoxin-associated gene A


CHCChronic hepatitis C

CINCervical intraepithelial neoplasia

CSClonorchis sinensis

EBERsEBV-encoded RNAs

EBVEpstein-Barr virus

EGFREpidermal growth factor receptor

EMTEpithelial-mesenchymal transition

eNOSEndothelial NO synthase

H. pyloriHelicobacter pylori

HBVHepatitis B virus

HCVHepatitis C virus

HIV-1Human immunodeficiency virus-1

HPVHuman papillomavirus

HSP70.1Heat shock protein 70-kDa protein 1

HTLV-1Human T-cell lymphotropic virus type 1

IARCInternational Agency for Research on Cancer


INFInterferon therapy

iNOSInducible NO synthase

LMP1Latent membrane protein 1

MALTMucosa-associated lymphoid tissue

MARKMicrotubule affinity-regulating kinase

nNOSNeuronal NO synthase

NONitric oxide

Nod1Nucleotide-binding oligomerization domain protein 1

NPCNasopharyngeal carcinoma



OVOpisthorchis viverrini

PAR1Partitioning-defective 1

PI3K-AKTPhosphoinositide 3-kinase-protein kinase B

RNSReactive nitrogen species

ROSReactive oxygen species

SHSchistosoma haematobium

SHP2Src homology 2 domain-containing phosphatase 2

STAT3Signal transducer and activator of transcription-3

TNF-αTumor necrosis factor-α

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Autor: Shosuke Kawanishi - Shiho Ohnishi - Ning Ma - Yusuke Hiraku - Shinji Oikawa - Mariko Murata


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