• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3047-3052
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• 2012

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.

• Toxicological Research
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• 제17권
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• pp.293-297
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• 2001

The international pharmaceutical and regulatory communities had been recognizing the limited utility of conventional rodent carcinogenicity study particularly on the second species, mouse, after intense investigation of carcinogenicity data base worldwide, and a new scheme for carcinogenicity testing for pharmaceuticals was proposed at the Expert Working Group on Safety in the International Conference on Harmonization (ICH) in 1996. CB6F 1-Tg rasH2 mouse carrying human prototype c-Ha-ras gene with its own promoter/enhancer is one oj the new carcinogenicity assay model for human cancer risk assessment. Studies have been conducted since 1992 to validate the transgenic (Tg) mice for rapid carcinogenicity test-ing, short term (26 weeks) studies with genotoxic (by Salmonella), non-genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic non-carcinogens revealed relatively high concordance oj the response of the Tg mouse with classical bioassay across classes of carcinogenic agents. Mechanistic basis for carcinogensis in the model are being elucidated in terms of the role of overexpression and/or point mutation of the transgene. This report review the initial studies of validation of the model and preliminary results of on-going ILSI HESI ACT project will be presented.

• 환경영향평가
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• 제29권5호
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• pp.391-402
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• 2020

국내 법적 근거를 가진 건강영향평가(Health Impact Assessment)는 환경영향평가 항목 중 위생공중보건 항목에서 작성 수행되고 있다. 택지개발 등 주거지 개발사업들은 「환경보건법」 제13조에 따른 건강 영향평가 대상사업은 아니다. 하지만 환경영향평가협의회 단계에서 인근 산업단지 등 오염원에서 배출되는 물질 중 건강영향평가 대상물질을 확인하여 위해도(발암·비발암 포함)를 산정하여 제시하라는 심의내용에 근거하여 부분적인 건강영향평가로 수행하고 있다. 주거지 개발사업은 특정대기유해물질 등 오염물질 배출시설 계획이 없지만 주변 산업단지와 같은 대기오염 발생원에서 배출되는 오염물질에 의해 향후 입주하는 계획지구 주민들에게 건강영향을 미칠 수가 있다. 본 연구에서는 실제 도시개발사업 사례를 분석하여 미래에 입주하는 계획지구 입주민들에게 미치는 영향을 검토하고자 하였다. 미래에 영향 검토 시 주변지역에 대한 문헌을 통한 예측 case1, 대기확산모델(AERMOD)을 이용한 발암성물질 노출농도예측과 기여도 분석 case2를 하였다. 본 연구를 통해 계획지구 인근 산업단지 등의 오염원에 대한 수용체를 고려한 건강영향평가 방법으로는 현황조사와 대기확산모델(AERMOD)을 이용한 노출농도예측 및 기여도분석을 상호 보완적으로 적용하여 평가하는 것이 효용성이 높은 것으로 판단되었다.

• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.275-284
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• 1998

1996년 3월부터 1996년 12월까지 충북대학교병원 비뇨기과에 입원하여 치료를 받은 방광암 환자 67명과 암 아닌 다른 질환을 가진 대조군 67명을 대상으로 흡연, 음주, 직업력 등을 포함한 생활 습관과 NAT2와 GSTM1, 그리고 GSTT1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. NAT2 다형성 분포는, 환자군이 slow, intermediate, rapid acetylator가 각각 3.0%, 38.8%, 58.2%, 그리고 대조군이 7.6%, 40.9%, 51.5%였으며, NAT2의 활성과 방광암 위험도 사이의 관련성은 유의하지 않았다($\chi^2_{trend}=1.18$, P-value>0.05). 2. GSTM1 결손은 환자군의 68.7%, 대조군의 49.3%에서 확인되었으며, OR(95% 신뢰구간)이 2.23(1.12-4.56)으로, 방광암 발생의 위험인자로 나타났다. 3. GSTT1은 환자군의 26.9%,그리고 대조군의 43.3%에서 결손이 있는 것으로 나타나서, GSTT1 결손은 방광암에 대하여 보호효과가 있는 것으로 관찰되었다(OR: 0.48, 95% 신뢰구간: 0.23-0.99). 4. 흡연 여부는 방광암의 발생에 유의한 영향을 미치지 않는 것으로 나타났는데(OR=1.85, 95% CI: 0.85-4.03), 이는 환자군과 대조군의 흡연률이 모두 높기 때문으로 판단된다. 5. 그 외, 음주력, 직업력, 수혈 여부, 그리고 피임시술의 과거력 등의 요인들은 방광암 발생과 유의한 관련성이 없는 것으로 나타났다.

• Asian Journal of Atmospheric Environment
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• 제8권1호
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• pp.35-47
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• 2014

The purpose of the study is to evaluate the pollution level (gaseous and particle phase) in the public facilities for the PAHs, non-regulated materials, forecast the risk level by the health risk assessment (HRA) and propose the guideline level. PAH assessments through sampling of particulate matter of diameter < 2.5 ${\mu}m$ ($PM_{2.5}$). The user and worker exposure scenario for the PAHs consists of 24-hour exposure scenario (WIES) assuming the worst case and the normal exposure scenario (MIES) based on the survey. This study investigated 20 PAH substances selected out of 32 substances known to be carcinogenic or potentially carcinogenic. The risk assessment applies major toxic equivalency factor (TEF) proposed from existing studies and estaimates individual Excess Cancer Risk (ECR). The study assesses the fine dusts ($PM_{2.5}$) and the exposure levels of the gaseous and particle PAH materials for 6 spots in each 8 facility, e.g. underground subway stations, child-care facilities, elderly care facilities, super market, indoor parking lot, terminal waiting room, internet caf$\acute{e}$ (PC-rooms), movie theater. For internet caf$\acute{e}$ (PC-rooms) in particular, that marks the highest $PM_{2.5}$ concentration and the average concentration of 10 spots (2 spots for each cafe) is 73.3 ${\mu}g/m^3$ (range: 6.8-185.2 ${\mu}g/m^3$). The high level of $PM_{2.5}$ seen in internet cafes was likely due to indoor smoking in most cases. For the gaseous PAHs, the detection frequency for 4-5 rings shows high and the elements with 6 rings shows low frequency. For the particle PAHs, the detection frequency for 2-3 rings shows low and the elements with 6 rings show high frequency. As a result, it is investigated that the most important PAHs are the naphthalene, acenaphthene and phenanthrene from the study of Kim et al. (2013) and this annual study. The health risk assessment demonstrates that each facility shows the level of $10^{-6}-10^{-4}$. Considering standards and local source of pollution levels, it is judged that the management standard of the benzo (a)pyrene, one of the PAHs, shall be managed with the range of 0.5-1.2 $ng/m^3$. Smoking and ventilation were considered as the most important PAHs exposure associated with public facility $PM_{2.5}$. This study only estimated for inhalation health risk of PAHs and focused on the associated cancer risk, while multiple measurements would be necessary for public health and policy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5249-5252
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• 2014

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

• 한국식품위생안전성학회지
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• 제35권4호
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• pp.354-364
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• 2020

서울약령시장과 서울경동시장 등에서 유통되고 있는 식약공용 농·임산물 29품목 171건에 대하여 ICP-MS와 수은 분석기를 이용하여 중금속(납, 카드뮴, 비소, 수은) 함량을 분석하고 위해도를 평가하였다. 납, 카드뮴, 비소, 수은의 검출 범위는 각각 ND-4.719 mg/kg, ND-1.019 mg/kg, 0.002-8.696 mg/kg, ND-0.058 mg/kg로 나타났다. 171건의 검체 중 Artemisiae Capillaris Herba(인진호) 1건과 Actinidiae Ramulus et Fulium et Fructus Vermicultus(목천료) 1건에서 각각 카드뮴과 비소 항목이 허용기준을 초과하여 부적합 판정을 받았으며 나머지는 모두 허용기준 이내였다. 위해도를 평가 했을 때 비발암위해도지수(HI)가 1을 초과한 품목은 없었고, 발암위해도가 납은 모든 품목에서 10^-6 이하였으며 비소는 10^-4-10^-6 으로 나타나 전반적으로 안전한 수준으로 평가되었다. %PTWI는 납, 카드뮴, 비소, 수은 모두 100이하로 나타났다. 유통중인 식약공용 농·임산물의 중금속(납, 카드뮴, 비소, 수은) 함량을 분석하고 비발암위해도지수(HI), 발암위해도, %PTWI를 평가한 결과 안전한 수준으로 평가되었다.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.12.1-12.8
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• 2012

Objectives: The aim of this study was to identify the health and environmental risk factors of air contaminants that influence environmental and respiratory diseases in Gyeongju, Pohang and Ulsan in South Korea, with a focus on volatile organic compounds (VOCs). Methods: Samples were collected by instantaneous negative pressure by opening the injection valve in the canister at a fixed height of 1 to 1.5 m. The sample that was condensed in $-150^{\circ}C$ was heated to $180^{\circ}C$ in sample pre-concentration trap using a 6-port switching valve and it was injected to a gas chromatography column. The injection quantity of samples was precisely controlled using an electronic flow controller equipped in the gas chromatography-mass spectrometer. Results: The quantity of the VOC emissions in the industrial area was 1.5 to 2 times higher than that in the non-industrial area. With regards to the aromatic hydrocarbons, toluene was detected at the highest level of 22.01 ppb in Ulsan, and chloroform was the halogenated hydrocarbons with the highest level of 10.19 ppb in Pohang. The emission of toluene was shown to be very important, as it accounted for more than 30% of the total aromatic hydrocarbon concentration. Conclusions: It was considered that benzene in terms of the cancer-causing grade standard, toluene in terms of the emission quantity, and chloroform and styrene in terms of their grades and emission quantities should be selected for priority measurement substances.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6429-6438
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• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• BMB Reports
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• 제51권11호
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.