Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening:A multicenter randomized controlled trial in different resource settings in China

Objective:We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus(hrHPV)-positive women in primary healthcare settings in China.Methods:This study was undertaken in 11 rural and 9 urban sites.Women aged 35-64 years old were enrolled.HrHPV-positive women were randomly allocated to liquid-based cytology(LBC),visual inspection with acetic acid and Lugol’s iodine(VIA/VILI)(rural only)triage,or directly referred to colposcopy(direct COLP).At 24 months,hrHPV testing,LBC and VIA/VILI were conducted for combined screening.Results:In rural sites,1,949 hrHPV-positive women were analyzed.A total of 852,218 and 480 women were randomly assigned to direct COLP,LBC and VIA/VILI.At baseline,colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%.LBC(n=3 and n=7)or VIA/VILI(n=8 and n=26)could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia(CIN)2 or worse and CIN3+compared with direct COLP(n=14 and n=23).For the 24-month cumulative detection rate of CIN2+,VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP.When stratified by age,baseline LBC triage+performed best(P<0.001),peaking among women aged 35-44 years(Ptrend=0.002).In urban sites,1,728 women were hrHPV genotyping test positive.A total of 408,571 and 568women were randomly assigned to direct COLP for HPV16/18+,direct COLP for other hrHPV subtypes+,and LBC triage for other hrHPV subtypes+.LBC(n=12 and n=31)significantly decreased the number of colposcopies needed to detect one CIN2+and CIN3+compared with direct COLP(n=14 and n=44).HPV16/18+increased the 24-month cumulative detection rate of CIN2+(17.89%,P<0.001).Conclusions:LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+women and LBC triage for other hrHPV subtype+women in urban settings might be feasible strategies.

Chemo/Dietary prevention of cancer:perspectives in China

Cancer is a major disease worldwide and different approaches are needed for its prevention.Previous laboratory and clinical studies suggest that cancer can be prevented by chemicals,including those from the diet.Furthermore,epidemiological studies have suggested that deficiencies in certain nutrients can increase the risk of some cancers.In this article on chemo/dietary prevention,examples will be given to illustrate the effectiveness of chemopreventive agents in the prevention of breast,colon and prostate cancers in high-risk populations and the possible side effects of these agents.The potential usefulness of dietary approaches in cancer prevention and the reasons for some of the failed trials will be discussed.Lessons learned from these studies can be used to design more relevant research projects and develop effective measures for cancer prevention in the future.The development of effective chemopreventive agents,the use of nutrient supplements in deficient or carcinogen-exposed populations,and the importance of cohort studies will be discussed in the context of the current socioeconomic situation in China.More discussions are needed on how we can influence society to pay more attention to cancer prevention research and measures.

Patterns and Trends in Diagnostic Tests Used for Detection of Colorectal Cancer after Screening with the Immunochemical Fecal Occult Blood Test in Japan

According to the guidelines by the Japanese government, optical colonoscopy is the most strongly recommended diagnostic test after screening with the immunochemical fecal occult blood test (iFOBT), followed by double-contrast barium enema (BE) or sigmoidoscopy. Our study was to assess patterns and trends of colorectal cancer (CRC) diagnostic testing within 2 years after iFOBT. We analyzed both iFOBT results and claims data provided by employee health insurance societies in Japan from 2005 to 2010. 25,596 enrollees underwent iFOBT screening. The positive rate was 5.1%. 32.3% of those positive underwent diagnostic tests and 1.0% (12 patients) were confirmed as having cancer. The most common test was optical colonoscopy (77.2% of total tests), followed by BE (16.2%). From 2006 to 2009, the rate of optical colonoscopy for females increased from 55% to 82% and that of BE declined from 36% to 12%, while no significant changes were seen for males. Only one-third of those who tested positive underwent diagnostic test in the 2 years following screening iFOBT. As official guidelines for diagnostic testing of CRC recommend, optical colonoscopy is now the most commonly used diagnostic test after positive iFOBT result for enrollees in employee health insurance societies in Japan.

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Current issues and future perspectives of gastric cancer screening

Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries,which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques,namely,upper gastrointestinal endoscopy,serological testing,and "screen and treat" method were extensively reviewed. Moreover,the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand,serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date,the effectiveness of new techniques for gastric cancer screening has remained limited. However,endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening.To effectively introduce new techniques for gastric cancer screening in a community,incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies.In addition to effectiveness evaluation,the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening.

Comparative epidemiology of gastric cancer between Japan and China

AIM:To clarify the similarities and differences in gastric cancer epidemiology between Japan and China.METHODS:A comprehensive literature search of the PubMed database was performed.The relevant literature published in China was also been cited.Data on incidence and mortality rates in 2008 were obtained from the Cancer Mondial database,published by International Agency for Research on Cancer at http://www-dep.iarc.fr/.RESULTS:Gastric cancer remains a significant publichealth burden in both Japan and China.The prevalence of Helicobacter pylori(H.pylori)colonization is high in the adult populations of both countries.Accumulating evidence from intervention studies in both countries has shown the effectiveness of H.pylori eradication in reduc-ing gastric cancer incidence.There are differences,however,in many aspects of gastric cancer,including patterns of incidence and mortality,trends in the prevalence of H.pylori infection,H.pylori strains,the magnitude of risk of gastric cancer related to H.pylori infection,and associations with dietary habits.Compared with China,Japan has seen a more rapid decline in H.pylori infection among adolescents.While Japanese cohort studies have dominated the literature concerning the associations between gastric cancer and dietary habits,numerous case-control studies in China suggest a positive association between a high intake of preserved fish and vegetables and gastric cancer risk.There is a need for a multidisciplinary research approach to understand the interactions between various strains of H.pylori,host factors,and other lifestyle and environmental factors in gastric carcinogenesis in both countries.CONCLUSION:The shared high incidence of gastric cancer and high prevalence of H.pylori,as well as differences in many aspects of gastric cancer,provide an excellent opportunity to establish Sino-Japanese collaborations.

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.

Impact of endoscopic screening on mortality reduction from gastric cancer

AIM:To investigate mortality reduction from gastric cancer based on the results of endoscopic screening.METHODS:The study population consisted of participants of gastric cancer screening by endoscopy,regular radiography,and photofluorography at Niigata city in 2005.The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry.The standardized mortality ratio(SMR)of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population.RESULTS:Based on the results calculated from the mortality rate of the population of Niigata city,the SMRs of gastric cancer death were 0.43(95%CI:0.30-0.57)for the endoscopic screening group,0.68(95%CI:0.55-0.79)for the regular radiographic screening group,and 0.85(95%CI:0.71-0.94)for the photofluorography screening group.The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer.CONCLUSION:The 57%mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer.Further studies and prudent interpretation of results are needed.

New insights into pancreatic cancer stem cells

Pancreatic cancer(PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells(CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on Dcl K1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC.

Predictors for difficult cecal insertion in colonoscopy: The impact of obesity indices

AIM To identify the factors influencing cecal insertion time(CIT) and to evaluate the effect of obesity indices on CIT. METHODS We retrospectively reviewed the data for participants who received both colonoscopy and abdominal computed tomography(CT) from February 2008 to May 2008 as part of a comprehensive health screening program. Age, gender, obesity indices [body mass index(BMI), waist-to-hip circumference ratio(WHR), waist circumference(WC), visceral adipose tissue(VAT)volume and subcutaneous adipose tissue(SAT) volume on abdominal CT], history of prior abdominal surgery, constipation, experience of the colonoscopist, quality of bowel preparation, diverticulosis and time required to reach the cecum were analyzed. CIT was categorized as longer than 10 min(prolonged CIT) and shorter than or equal to 10 min, and then the factors that required a CIT longer than 10 min were examined.RESULTS A total of 1678 participants were enrolled. The mean age was 50.42 ± 9.931 years and 60.3% were men. The mean BMI, WHR, WC, VAT volume and SAT volume were 23.92 ± 2.964 kg/m2, 0.90 ± 0.076, 86.95 ± 8.030 cm, 905.29 ± 475.220 cm3 and 1707.72 ± 576.550 cm3, respectively. The number of patients who underwent abdominal surgery was 268(16.0%). Colonoscopy was performed by an attending physician alone in 61.9% of cases and with the involvement of a fellow in 38.1% of cases. The median CIT was 7 min(range 2-56 min, IQR 5-10 min), and mean CIT was 8.58 ± 5.291 min. Being female, BMI, VAT volume and involvement of fellow were significantly associated with a prolonged CIT in univariable analysis. In multivariable analysis, being female(OR = 1.29, P = 0.047), lower BMI(< 23 kg/m2)(OR = 1.62, P = 0.004) or higher BMI(≥ 25 kg/m2)(OR = 1.80, P < 0.001), low VAT volume(< 500 cm3)(OR = 1.50, P = 0.013) and fellow involvement(OR = 1.73, P < 0.001) were significant predictors of prolonged CIT. In subgroup analyses for gender, lower BMI or higher BMI and fellow involvement were predictors for prolonged CIT in both genders. However, low VAT volume was associated with prolonged CIT in only women(OR = 1.54, P = 0.034).CONCLUSION Being female, having a lower or higher BMI than the normal range, a low VAT volume, and fellow involvement were predictors of a longer CIT.

Trend Analysis of Cancer Mortality in the Jinchang Cohort, China,2001-2010

Objective To describe the baseline data of cancers in the Jinchang Cohort, this paper examined trends in cancer mortality among adults investigated in Jinchang, Gansu province from 2001 to 2010. Methods Mortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010. Results The crude mortality rate of cancer continuously increased from 161.86 per 100,000 in 2001 to 315.32 per 100,000 in 2010, with an average increase of 7.69% per year in the Jinchang Cohort （16.41% in females compared to 6.04% in males）, but the age-standardized mortality rate increased only in females. Thirteen leading cancers accounted for 92.10% of all cancer deaths. The five leading causes of cancer mortality in males were lung, gastric, liver, esophageal, and colorectal cancer, whereas those in females were lung, liver, gastric, breast, and esophageal cancer. Conclusion The overall cancer mortality rate increased from 2001 to 2010 in the Jinchang Cohort, with greater rate of increase in females than in males. Lung, breast, and gastric cancer, in that order, were the leading causes of increased cancer mortality in females.

Successful endoscopic closure of a colonic perforation one day after endoscopic mucosal resection of a lesion in the transverse colon

A 73-year-old man underwent endoscopic mucosal resection(EMR) of a 20-mm flat elevated lesion on the transverse colon. The morning after the procedure, he started to have severe right upper quadrant pain after his first meal. A computed tomography scan revealed free air and a stomach filled with food. He was diagnosed to have delayed post-EMR intestinal perforation. He underwent emergent colonoscopy and clipping of the perforated site. He was discharged 8 d after the endoscopic closure without the need for surgical intervention. The meal was not the cause of the colon transversum perforation.

Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region, China, 2018

Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends（＋2.63% per year; P 〈 0.05 and ＋1.9% per year; P 〈 0.05）. This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.

Three novel NEIL1 promoter polymorphisms in gastric cancer patients

AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric cancer was searched for genetic polymorphisms by polymerase chain reaction-single-strand conformation polymorphism and subsequent sequencing analyses.RESULTS:Three novel genetic polymorphisms,i.e.c.-3769C>T,c.-3170T>G,and c.-2681TA[8],were identified in the NEIL1 promoter region at an allele frequency of 0.6%,9.4%,and 4.4%,respectively,in Japanese gastric cancer patients.CONCLUSION:Three NEIL1 promoter polymorphisms detected in this study may be of importance in gastric carcinogenesis.

Analysis of the Prognosis for Patients with Stage T3N0-1M0 Nasopharyngeal Carcinoma Treated by Chemotherapy Combined with Radiotherapy

OBJECTIVE To investigate the relationship between the therapeutic modality and prognostic factors for the patients with T3N0-1M0 nasopharyngeal carcinoma. METHODS The clinical data from 127 cases of T3N0-1M0 nasopharyngeal carcinoma patients with initial treatment, during the period from January 4th, 2000 to November 12th, 2001, were retrospectively analyzed. The cases were divided into Group A with simple radiotherapy (90) and Group B with the radiation therapy combined with chemotherapy (37), based on various patients' conditions. In group B, inductive chemotherapy was conducted for 18 cases, inductive chemotherapy plus homochronous chemotherapy for 5 and homochronous chemotherapy for 14. RESULTS The 5-year overall survival (OS) in the groups A and B was 73.4% and 72.3% respectively (P>0.05); the cancer-correlated survival (CCS) in the 2 groups was 76.4% and 72.3% respectively (P>0.05); the disease-free survival (DFS) in group A and B was 65.5% and 71.7% respectively (P<0.05). A multiple analysis showed that the mode of radiation therapy plus chemotherapy was a favorable independent impact factor for DFS. CONCLUSION Chemotherapy plus radiotherapy can improve the DFS of patients with T3N0-1M0 nasopharyngeal carcinoma, but fails to prolong the survival time of the patients. The modality of chemotherapy plus radiotherapy is not the necessary choice in treatment of patients with T3N0-1M0 nasopharyngeal carcinoma.

Mitochondria-targeted atovaquone promotes anti-lung cancer immunity by reshaping tumor microenvironment and enhancing energy metabolism of anti-tumor immune cells

Dear Editor,Atovaquone(ATO),a mitochondrial inhibitor,has anti-cancer effects[1].Based on ATO,we developed mitochondria-targeted atovaquone(Mito-ATO)that had even stronger anti-tumor efficacy than ATO[2].We syn-thesized Mito-ATO by attaching the bulky triphenylphos-phonium(TPP)group to ATO via a ten-carbon alkyl chain(Supplementary file of methods;Supplementary Figure S1).

Reinfection rate and endoscopic changes after successful eradication of Helicobacter pylori

AIM:To determine the long-term outcomes regarding reinfection with Helicobacter pylori(H.pylori)and endoscopic changes after successful H.pylori eradication. METHODS:From June 1994 to January 2007,186 patients(M:F=98:88;mean age 50.0±11.4 years), in whom H.pylori had been successfully eradicated, were enrolled.The mean duration of follow up was 41.2±24.0 mo. RESULTS:H.pylori reinfection occurred in 58 patients (31.2%).The average annual reinfection rate was 9.1% per patient year.No recurrence of peptic ulcer was detected at the follow up endoscopy.There were no significant differences between the H.pylori eradication regimens for the reinfection rate and no significant differences in endoscopic findings between the H.pylorirecurred group and the H.pylori-cured group.CONCLUSION:The reinfection rate in Korea is 9.1% which represents a decreasing trend.There was no relationship between H.pylori infection status and changes in endoscopic findings.There was also no recurrence or aggravation of ulcers.

BRIEF ARTICLE New reduced volume preparation regimen in colon capsule endoscopy

AIM:To evaluate the effectiveness of our proposed bowel preparation method for colon capsule endoscopy.METHODS:A pilot,multicenter,randomized controlled trial compared our proposed "reduced volume method"(group A) with the "conventional volume method"(group B) preparation regimens.Group A did not drink polyethylene glycol electrolyte lavage solution(PEGELS) the day before the capsule procedure,while group B drank 2 L.During the procedure day,groups A and B drank 2 L and 1 L of PEG-ELS,respectively,and swallowed the colon capsule(PillCam COLON capsule).Two hours later the first booster of 100 g magnesium citrate mixed with 900 mL water was administered to both groups,and the second booster was administered six hours post capsule ingestion as long as the capsule had not been excreted by that time.Capsule videos were reviewed for grading of cleansing level,RESULTS:Sixty-four subjects were enrolled,with results from 60 analyzed.Groups A and B included 31 and 29 subjects,respectively.Twenty-nine(94%) subjects in group A and 25(86%) subjects in group B had adequate bowel preparation(ns).Twenty-two(71%) of the 31 subjects in group A excreted the capsule within its battery life compared to 16(55%) of the 29 subjects in group B(ns).Of the remaining 22 subjects whose capsules were not excreted within the battery life,all of the capsules reached the left side colon before they stopped functioning.A single adverse event was reported in one subject who had mild symptoms of nausea and vomiting one hour after starting to drink PEG-ELS,due to ingesting the PEG-ELS faster than recommended.CONCLUSION:Our proposed reduced volume bowel preparation method for colon capsule without PEG-ELS during the days before the procedure was as effective as the conventional volume method.

A Retrospective Cohort Mortality Study in Jinchang,the Largest Nickel Production Enterprise in China

Nickel is an essential trace metal used in the occupational setting, resulting in both occupational and nonoccupational exposures to individuals at varying levels. Exposure to nickel has been associated with several toxicities and the International Agency for Research on Cancer has concluded that there is sufficient evidence in humans associating exposure to nickel compounds with risk of lung cancer and sinonasal cancer. This study confirmed a significant excess of mortality from diseases of the lung including silicosis, lung cancer, and cor pulmonale among workers involved in nickel mining or smelting in China.

Dynamic Changes in DNA Damage and Repair Biomarkers with Employment Length among Nickel Smelting Workers

Our study explored the dynamic changes in andthe relationship between the DNA damage marker8-hydroxy-2＇-deoxyguanosine （8-OHdG） and theDNA repair marker 8-hydroxyguanine DNAglycosidase 1 （hOGG1） according to the length ofoccupational employment in nickel smeltingworkers. One hundred forty nickel-exposedsmelting workers and 140 age-matched unexposedoffice workers were selected from the Jinchangcohort. The 8-OHdG levels in smelting workers wassignificantly higher than in office workers （Z=-8.688,P〈0.05） and the 8-OHdG levels among nickelsmelting workers in the 10-14 y employment lengthcategory was significantly higher than among allpeers. The hOGG1 levels among smelting workerswere significantly lower than those of non-exposedworkers （Z=-8.948, P〈0.05）. There were significantdifferences between employment length andhOGG1 levels, with subjects employed in nickelsmelting for 10-14 y showing the highest levels ofhOGG1. Correlation analysis showed positivecorrelations between 8-OHdG and hOGG1 levels（r=0.413; P〈0.01）. DNA damage was increased withemployment length among nickel smelting workersand was related to the inhibition of hOGG1 repaircapacity.