Journal of Preventive Medicine and Public Health

Original Article

Association Between MicroRNA196a2 rs11614913 Genotypes and the Risk of Non-Small Cell Lung Cancer in Korean Population: Young-Seoub Hong, Ho-Jin Kang, Jong-Young Kwak, Byung Lae Park, Chang-Hun You, Yu-Mi Kim, Heon Kim; J Prev Med Public Health. 2011;44(3):125-130. Published online May 17, 2010; DOI: https://doi.org/10.3961/jpmph.2011.44.3.125

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Objectives

The microRNA (miRNA) miR-196a2 may play an important role in lung cancer development and survival by altering binding activity of target mRNA. In this study, we evaluated their associations with the susceptibility of non-small cell lung cancers (NSCLC) by case-control study in a Korean population.

Methods

We performed genotyping analyses for miR-196a2 rs11614913 T/C at miRNA regions in a case-control study using blood samples of 406 NSCLC patient and 428 cancer-free control groups.

Results

The total C allele frequencies for miR-196a2 were 48.8% for the patients and 45.6% for the controls; and the genotype frequencies of TT, TC, and CC were 23.7%, 55.2%, and 21.1% for the patients and 31.1%, 46.35%, and 22.4% for the controls (p<0.05). Participants who possesses TC/CC genotypes showed high risk for NSCLC compared to those possessed TT genotypes (OR, 1.42; 95% CI, 1.03 to 1.96). The association was persisted in 60 and older age group, male, smokers, those without family history for cancer. However, no significant association of CC genotypes in recessive genetic model was observed.

Conclusions

In conclusion, this case-control study provides evidence that miR-196a2 rs11614913 C/T polymorphisms are associated with a significantly increased risk of NSCLC in a dominant model, indicating that common genetic polymorphisms in miR-196a2 rs11614913 are associated with NSCLC. The association of miR196a2 rs11614913 polymorphisms and NSCLC risk require confirmation through additional larger studies.

Summary

Citations

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Editorial

Association Between Green Tea Consumption and Lung Cancer Risk.: Andy H Lee, Wenbin Liang, Fumi Hirayama, Colin W Binns; J Prev Med Public Health. 2010;43(4):366-367.; DOI: https://doi.org/10.3961/jpmph.2010.43.4.366

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Abstract PDF

Green tea is a popular beverage and its health benefits are well known. However, inconsistent results have been reported in observational studies concerning the association between green tea consumption and the lung cancer risk. In this commentary, several methodological issues underlying the measurement of tea exposure are highlighted. The recommendations should be useful for designing and planning prospective cohort studies to ascertain the protective effect of green tea against lung cancer.

Summary

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English Abstract

Ten Year Trend of Cancer Incidence in Seoul, Korea: 1993-2002.: Myung Hee Shin, Hyun Kyung Oh, Yoon Ok Ahn; J Prev Med Public Health. 2008;41(2):92-99.; DOI: https://doi.org/10.3961/jpmph.2008.41.2.92

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Abstract PDF

OBJECTIVES
Effective cancer prevention and control measures can only be done when dependable data on the cancer incidence is available. The Seoul Cancer Registry (SCR) was founded to provide valid, comparable and representative cancer incidence data for Koreans. We aimed to compare the cancer incidence in the first (1993-1997) and second term (1998-2002) of the SCR, and we analyzed the annual incidence trend during that 10 years. METHODS: The SCR detects potential cancer cases through the Korean Central Cancer Registry (KCCR) data, the health insurance claims, the individual hospital's discharge records and the death certificates. About 87% of the SCR data is registered through the KCCR. The rest of the data is registered by SCR registrars who visit about 70~80 mid-sized hospitals in Seoul to review and abstract the medical records of the potential cancer patients. RESULTS: The total number of new cancer cases was higher in 1998~2002 than in 1993~1997 by 20.6% for men and 18.4% for women, respectively. The age-standardized rate (ASR) of total cancer per 100,000 increased 1% (from 295.4 to 298.3) for men and 5.1% (from 181.5 to 190.7) for women, between the two periods. The commonest cancer sites during 1998-2002 for men were stomach, liver, bronchus/lung, colorectum, bladder and prostate, and the commonest cancer sites for women were breast, stomach, colorectum, cervix uteri, thyroid and bronchus/lung. Compared with the ASRs in 1993, the ASRs in 2002 increased for colorectum (58.4% for men, 27.1% for women), prostate (81.5%), breast (58.3% for women), thyroid (141% for women), and bronchus/lung (15.4% for women). The ASRs for stomach (-18.7% for men, -20.7% for women) and uterine cervix cancer (-39.7%) had decreased. CONCLUSIONS: The cancer incidence is increasing in Seoul, Korea, especially for the colorectum and prostate for men, and for the breast, colorectum, bronchus/lung and thyroid for women.

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Original Articles

Therapeutic Compliance and Its Related Factors of Lung Cancer Patients.: Si Hyun Nam, Sin Kam, Jae Yong Park, Sang Chul Chae, Moon Seob Bae, Moo Chul Shin, Min Hae Yeh; Korean J Prev Med. 2002;35(1):13-23.

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Abstract PDF: OBJECTIVES
To investigate the therapeutic compliance and its related factors in lung cancer patients. METHODS: The subjects of this study comprised 277 patients first diagnosed with lung cancer at Kyungpook National University Hospital between Jan 1999 and Sept 1999. Of these, 141 (50.9%) participated in the study by properly replying to structured questionnaires. The data was analyzed using a simplified Health Decision Model. This model includes categories of variables covering therapeutic compliance, health beliefs, patient preferences, knowledge and experience, social interaction, sociodemographic and clinical characteristics. RESULTS: The therapeutic compliance rate of the 141 study subjects was 78.0%. An analysis of health beliefs and patient preferences revealed health concern (p<0.05), dependency on medicine (p<0.05), perceived susceptibility and severity (p<0.05) as well as preferred treatment (p<0.01) as factors related to therapeutic compliance. Factors from the sociodemographic characteristics and clinical factors that were related to therapeutic compliance were age (p<0.01), monthly income (p<0.05), histological type (p<0.05) and clinical stage (p<0.05) of cancer. CONCLUSIONS: In order to improve therapeutic compliance in lung cancer patients it is necessary to educate the aged, low-income patients, or patients who have small cell lung cancer or lung cancer of an advanced stage for which surgery is not indicated. Additionally, it is essential for medical personnel to have a deep concern about patients who have poor lifestyles, a low dependency on medicine, or a high perceived susceptibility and severity. Practically, early diagnosis of lung cancer and thoughtful considerations of low-income patients are important. By means of population-based education in a community, we may promote attention to health and enhance the early diagnosis of lung cancer.; Summary

Understanding the Occurrence of Lung Cancer in Foundry Workers through Health Insurance Data .: Yeon Soon Ahn, Jae Seok Song, Seong Kyu Kang, Ho Keun Chung; Korean J Prev Med. 2000;33(3):299-305.

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Abstract PDF: CONCLUSIONS: To investigate the difference in the occurrence of lung cancer between foundry workers and non-foundry workers by comparing the number of workers diagnosed with lung cancer through health insurance data. METHODS: The study population was comprised of 28,884 workers who had undergone at least one general or special medical examination between January 1995 and December 1997 at the occupational health center. All of the subjects had health insurance during this period. We combined the medical examination data with the health insurance data to compare the number of foundry workers diagnosed with lung cancer and the number of non-foundry workers diagnosed with lung cancer. RESULTS: Seven workers were diagnosed with lung cancer among the 1,591 foundry workers, compared to twelve workers among the 27,293 non-foundry workers (odds ratio: 10.04, 95% confidence interval: 3.95-25.55). The seven foundry workers diagnosed with lung cancer were all exposed to dust, and six out these seven workers were engaged in finishing or shake-out processes. CONCLUSIONS: Although the information for this study was obtained from health insurance data, which has limitations such as accuracy and completeness, the number of foundry workers diagnosed with lung cancer was significantly higher than that of non-foundry workers. Therefore, a well-designed cohort study should be followed to confirm the higher lung cancer rates in foundry workers.; Summary

A Case-Control Study on Effects of Genetic Polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 on Risk of Lung Cancer.: Hong Mei Nan, Heon Kim, Jong Won Kang, Jang Whan Bae, Kang Hyeon Choe, Ki Hyeong Lee, Seung Taik Kim, Choong Hee Won, Yong Min Kim; Korean J Prev Med. 1999;32(2):123-129.

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Abstract PDF: OBJECTIVES
This study was performed to investigate effects of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) on lung cancer development. METHODS: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital from March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung cancer were statistically analyzed. RESULTS: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls OR:1.43(0.81-2.51). The frequencies of Ile/Ile, Ile/Val and Val/Val of the CYP1A1 polymorphisms were 59.18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 (x2trend=0.253, p-value>0.05). The respective frequency of c1/c1, c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls (x2trend=5.783, p<0.05). c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% CI) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only smoking habit came out to be a significant risk factor for lung cancer. CONCLUSION: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.; Summary

PCR and RFLP-based CYP2D6(B) and CYP2D6(T) Genotyping for Korean Lung Cancer Cases and Controls.: Jin Ho Chun, Chang Hee Lee, Sang Hwa Urm, Byung Chul Son, Jun Han Park, Kui Oak Jung, Chang Hak Sohn, Hye Kyoung Yoon, Choon Hee Son, Hyung In Kim, Jin Seok Kim; Korean J Prev Med. 1998;31(1):1-14.

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Abstract PDF: The genetically determined CYP2D6 activity is considered to be associated with cancer susceptibility with inter-individual variation. Genetic polymorphism of CYP2D6(B) and CYP2D6(T) was determined by the two polymerase chain reaction(PCR) and BstN1 and EcoN1 restriction fragment length polymorphisms(RFLP) for 67 lung cancer cases and 95 healthy volunteer controls. The cases were composed of 26 squamous cell carcinoma, 14 small cell carcinoma, 10 adenocarcinoma, 3 large cell undifferentiated carcinoma, and 14 not histologically diagnosed. The results were gained from the 142 subjects (57 cases and 85 controls) who observed successfully in two PCR and BstN1/EcoN1 RFLP. Only one and no mutant allele of the CYP2D6(B) and CYP2D6(T) gene was detected, that is, the frequency of mutant allele was very low; 0.7%(1/142) and 0%(0/142), respectively. Detected mutant allele of the CYP2D6(B) was heterozygous type(WM). The odds ratios for lung cancer susceptibility with CYP2D6(B) and CYP2D6(T) genotype were not calculated. These results are similar to the previous understanding that the mutant allele is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6(B) and CYP2D6(T) genotypes have maybe no association with lung cancer susceptibility in Koreans. This is the basic data of CYP2D6(B) and CYP2D6(T) genotypes for Koreans. It would be hepful for further study to determine lung cancer susceptibility of Koreans with the data about CYP1A1, CYP2E1, GSTM1 from future study.; Summary

Lung cancer, chronic obstructive pulmonary disease and air pollution.: Joo Hon Sung, Soo Hun Cho, Dae Hee Kang, Keun Young Yoo; Korean J Prev Med. 1997;30(3):585-598.

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Abstract PDF: BACKGROUND
Although there are growing concerns about the adverse health effect of air pollution, not much evidence on health effect of current air pollution level had been accumulated yet in Korea. This study was designed to evaluate the chronic health effect of air pollution using Korean Medical Insurance Corporation (KMIC) data and air quality data. Medical insurance data in Korea have some drawback in accuracy, but they do have some strength especially in their national coverage, in having unified ID system and individual information which enables various data linkage and chronic health effect study. METHOD: This study utilized the data of Korean Environmental Surveillance System Study (Surveillance Study), which consist of asthma, acute bronchitis, chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (congestive heart failure and ischemic heart disease), all cancers, accidents and congenital anomaly, i.e., mainly potential environmental diseases. We reconstructed a nested case-control study with Surveillance Study data and air pollution data in Korea. Among 1,037,210 insured who completed questionnaire and physical examination in 1992, disease free (for chronic respiratory disease and cancer) persons, between the age of 35-64 with smoking status information were selected to reconstruct cohort of 564,991 persons. The cohort was followed-up to 1995 (1992-5) and the subjects who had the diseases in Surveillance Study were selected. Finally, the patients, with address information and available air pollution data, left to be 'final subjects'. Cases were defined to all lung cancer cases (424) and COPD admission cases (89), while control groups are determined to all other patients than two case groups among 'final subjects'. That is, cases are probable chronic environmental diseases, while controls are mainly acute environmental diseases. For exposure, Air quality data in 73 monitoring sites between 1991 - 1993 were analyzed to surrogate air pollution exposure level of located areas (58 areas). Five major air pollutants data, TSP, O3, SO2, CO, NOx was available and the area means were applied to the residents of the local area. 3-year arithmetic mean value, the counts of days violating both long-term and shot-term standards during the period were used as indices of exposure. Multiple logistic regression model was applied. All analyses were performed adjusting for current and past smoking history, age, gender. Results: Plain arithmetic means of pollutants level did not succeed in revealing any relation to the risk of lung cancer or COPD, while the cumulative counts of non-attainment days did. All pollutants indices failed to show significant positive findings with COPD excess. Lung cancer risks were significantly and consistently associated with the increase of O3and CO exceedance counts(to corrected error level - 0.017) and less strongly and consistently with SO2 and TSP. SO2and TSP showed weaker and less consistent relationship. O3and CO were estimated to increase the risks of lung cancer by 2.04 and 1.46 respectively, the maximal probable risks, derived from comparing more polluted area (95%) with cleaner area (5%). CONCLUSIONS: Although not decisive due to potential misclassication of exposure, these results were drawn by relatively conservative interpretation, and could be used as an evidence of chronic health effect especially for lung cancer. O3might be a candidate for promoter of lung cancer, while CO should be considered as surrogated measure of motor vehicle emissions. The control selection in this study could have been less appropriate for COPD, and further evaluation with another setting might be necessary.; Summary

Comparative Study

Effects of Oxidative DNA Damage and Genetic Polymorphism of the Glutathion Peroxidase 1 (GPX1) and 8-Oxoguanine Glycosylase 1 (hOGG1) on Lung Cancer.: Chul Ho Lee, Kye Young Lee, Kang Hyeon Choe, Yun Chul Hong, Sung Il Noh, Sang Yong Eom, Young Jun Ko, Yan Wei Zhang, Dong Hyuk Yim, Jong Won Kang, Heon Kim, Yong Dae Kim; J Prev Med Public Health. 2006;39(2):130-134.

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Abstract PDF: OBJECTIVES
Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. METHODS: Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. RESULTS: Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p<0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR=2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. CONCLUSIONS: These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.; Summary

English Abstract

Effects of Oxidative DNA Damage Induced by Polycyclic Aromatic Hydrocarbons and Genetic Polymorphism of the Paraoxonase-1 (PON1) Gene on Lung Cancer.: Chul Ho Lee, Kye Young Lee, Kang Hyeon Choe, Yun Chul Hong, Yong Dae Kim, Jong Won Kang, Heon Kim; J Prev Med Public Health. 2005;38(3):345-350.

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Abstract PDF: OBJECTIVE
Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. METHODS: One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8- hydroxydeoxyguanosine (8-OH-dG) measured. RESULTS: Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2- naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. CONCLUSIONS: These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene.; Summary

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