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      • SCOPUSKCI등재
      • KCI등재

        다환성 방향족 탄화수소 노출에 의한 DNA 산화적 손상과 Paraoxonase-1(PON1) 유전자 다형성이 폐암 발생에 미치는 영향

        이철호,이계영,최강현,홍윤철,김용대,강종원,김헌,Lee, Chul-Ho,Lee, Kye-Young,Choe, Kang-Hyeon,Hong, Yun-Chul,Kim, Yong-Dae,Kang, Jong-Won,Kim, Heon 대한예방의학회 2005 예방의학회지 Vol.38 No.3

        Objectives : 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.

      • KCI등재

        GPX1 및 hOGG1 유전자다형성에 따른 유전자의 산화적 손상 및 폐암 발생 위험도 평가

        이철호,이계영,최강현,홍윤철,노성일,엄상용,고영준,장연위,임동혁,강종원,김헌,김용대,Lee, Chul-Ho,Lee, Kye-Young,Choe, Kang-Hyeon,Hong, Yun-Chul,Noh, Sung-Il,Eom, Sang-Yong,Ko, Young-Jun,Zhang, Yan-Wei,Yim, Dong-Hyuk,Kang, Jong-Won,Kim, H 대한예방의학회 2006 예방의학회지 Vol.39 No.2

        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 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.

      • KCI등재후보

        주담관 ( Major Bile Ducts ) 을 침범한 간세포암에 대한 임상적 고찰

        박선미(Seon Me Park),최강현(Kang Hyeon Choe),진재용(Jae Yong Chin),김형호(Hyeong Ho Kim),김미경(Mee Kyung Kim),양석균(Suk Kyung Yang),정영화(Young Hwa Chung),이영상(Young Sang Lee),민영일(Young Il Min),이문규(Mun Gyu Lee),성규보(Kyu 대한내과학회 1993 대한내과학회지 Vol.45 No.5

        N/A Background: Hepatocellular carinoma (HCC) with major bile duct invasion is a particular type that invades and ruptures into the bile duct in the early stage of HCC. It will be different from the other types of HCC in the clinical characteristics, progonosis and prognostic factors. Method: We investigated 16 patients, who were confirmed to have major bile duct invation by surgical pathology (6 cases), cholangiogram (7 cases), or computed tomography (3 cases), to find clinical features and to evaluate prognosis and prognostic factors affecting the mean survival time. Results: 1) Sixteen (2.8%) of 566 patients with HCC were associated with major bile duct invasion. 2) The macroscopic types of tumor by computed tomography were nodular in 6, infiltrative in 8, and invisible in 2 cases. 3)The mean survival time of 16 patients was 3.3 months. 4) weight loss (>10%) and infiltrative tumor type were correlated to poor prognosis, However, age, total bilirubin, alpha-fetoprotein, and HBsAg positivity did not affect the survival time. Conclusion: In our series, the frequency of HCC with major bile duct invasion was not uncommon and the infiltrative tumor type was more frequent than the nodular tumor type. The assessment of weight loss and gross tumor type can identify some prospect of pro- longed survival in patients with HCC showing major bile duct invasion.

      • SCOPUSKCI등재

        GSTM1과 GSTT1, 그리고 CYP1A1, CYP2E1 다형성이 폐암발생에 미치는 영향에 대한 환자-대조군연구

        남홍매,강종원,배장환,최강현,이기형,김승택,원중희,김용민,김헌,Nan, Hong-Mei,Kang, Jong-Won,Bae, Jang-Whan,Choe, Kang-Hyeon,Lee, Ki-Hyeong,Kim, Seung-Taik,Won, Choong-Hee,Kim, Yong-Min,Kim, Heon 대한예방의학회 1999 예방의학회지 Vol.32 No.2

        1997년 3월부터 1998년 6월까지 충북대학교병원 내과에 입원하여 치료를 받은 폐암환자 98명과 암 아닌 다른 질환을 가진 대조군 98명을 대상으로 흡연, 음주, 여러 가지 질병과거력 등을 포함한 생활습관과, GSTM1과 GSTT1, 그리고 CYP1A1, CYP1E1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. GSTM1의 결손은 환자군이 67.01%, 대조군이 58.16%로 확인되었으며, OR(95% CI)이 1.46(0.82-2.62)으로 폐암 발생에 대해 유의한 영향을 미치지 않는 것으로 나타났다. 2. GSTT1의 결손은 환자군이 58.76%, 대조군이 50.00%로 확인되었으며, OR (95% CD가 1.43(0.81-2.51)으로 폐암 발생과 관련이 없는 것으로 나타났다. 3. CYP1A1 유전자 다형성은 Ile/Ile, Ile/Val, Val/Val 환자군이 각각 59.18%, 35.71%, 5.10%, 대조군이 각각 52.04%, 45.92%, 2.04%로 CYP1A1 유전자 다형성과 폐암 위험도 사이의 관련성은 유의하지 않은 것으로 나타났다$(x^2trend=0.253,\;p-value>0.05)$. 4. CYP1E1 유전자 다형성은 c1/c1, c1/c2, c2/c2 형 이 환자군에서 각각 50.00%, 42.86%, 7.14%, 대조군에서 각각 66.33%, 30.61%, 3.06%로 CYP1E1 활성이 폐암 발생에 유의한 영향을 미치는 것으로 나타났다$(x^2trend=5.783,\;p-value<0.05)$. 특히 환자군이 대조군에 비하여 아주 드문 대립유전자인 c2형이 더 많은 것으로 나타났다. 5. 폐암과 밀접한 연관이 있는 흡연습관의 OR(95% CI)이 3.03(1.58-5.81)으로 확인되어, 폐암의 위험인자로 재확인 되었다. 6. GSTM1, GSTT1, CYP1A1, CYP2-E1과 흡연습관을 포함한 다변량 분석에서 흡연습관만이 유의한 폐암의 위험인자로 나타났다. 이 결과로부터 위의 4가지 유전자의 다형성이 폐암발생에 미치는 영향은, 흡연을 포함한 환경적 요인에 비하여 크지 않을 것으로 판단된다. Objectives: This study was performed to investigate sweets of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytoehrome 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 form 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 rancor 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 lle/lle, lle/Val and Val/Val of the CYP1A1 polymorphisms were 59.18-18%, 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 ($x^2trend=0.253$, 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 $(x^2trend=5.783,\;p<0.05)$. 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% Cl) 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 snaking 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.

      • SCOPUSKCI등재

        Volume-Controlled Mode의 기계환기시 동일환 I:E Ratio하에서 Inspiratory Pause가 기도압 몇 가스교환에 미치는 영향

        최원준,정성한,이정아,최강현,Choi, Won-Jun,Jung, Sung-Han,Lee, Jeong-A,Choe, Kang-Hyeon 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.5

        연구배경: Volume controlled ventilation(VCV)시 inspiratory pause의 사용은 흡기시간을 연장하여 평균기도압을 상승시키고 가스교환을 호전시키는 것으로 알려져 있다. 그러나 같은 흡기시간을 유지하더라도 inspiratory pause를 사용하였을 경우 평균기도압과 가스교환의 변화에 대하여는 잘 알려지지 않았다. 방 법: 저자들은 VCV으로 기계호흡을 받는 12명의 환자를 대상으로 흡기산소농도, 상시호흡량, 호흡수 및 I : E ratio(1 : 3)는 변화시키지 않고 5%의 pause를 사용한 경우와 사용하지 않은 경우의 기도압 및 가스교환의 변화를 관찰하여 비교하였다. 결 과: 동맥혈 이산화탄소분압은 pause를 사용한 경우 $38.6{\pm}7.4$ mmHg로 시용하지 않은 경우의 $41.0{\pm}7.7$ mmHg보다 유의하게 낮았다 (p<0.01). 동맥혈 산소분압은 pause를 사용한 경우 $94.4{\pm}23.2$ mmHg로 사용하지 않은 경우의 $91.8{\pm}19.7$ mmHg보다 높은 경향이 있었으나 (p=0.054), 폐포-동맥혈 산소분압차$(P(A-a)O_2)$는 pause 유무에 따른 차이가 없었다 ($185.3{\pm}86.5$ mmHg vs. $184.9{\pm}84.9$ mmHg, P=0.766). 평균기도압은 pause를 사용한 경우 $9.7{\pm}4.0\;cmH_2O$로 사용하지 않은 경우의 $8.8{\pm}4.0\;cmH_2O$보다 유의하게 높았다 (p<0.01). Pause를 사용했을 때의 pause pressure와 pause를 사용하지 않을 때의 최고흡기압의 차이는 호흡기계의 저항과 역상관관계를 보였으나 (r=-0.777, p<0.01), pause가 없을 때의 최고흡기압에서 pause를 사용했을 때의 최고흡기압으로의 증가는 호흡기계의 저항과 정상관관계를 보여 (r=0.811, p<0.01), 평균기도압의 차이는 호흡기계의 저항과 유의한 정상관관계를 보였다(r=0.681, p<0.05). 평균기도압의 변화는 $PaCO_2$의 변화와 상관관계를 보이지 않았다. 결 론: Volume control ventilation시 동일한 1:3 의 I:E ratio하에서라도 5%의 inspiratory pause를 사용하는 것이 평균기도압을 더 높게 유지할 수 있으며 폐환기를 호전시킬 수 있는 것으로 사료되었다. 또한 호흡기계의 저항이 증가되어 있을수록 평균기도압의 상승이 많았으나 평균기도압의 상승 정도는 폐환기의 변화와 상관관계를 보이지 않았다. Background : In volume-controlled ventilation, the use of inspiratory pause increases the inspiratory time and thus increases mean airway pressure and improves ventilation. But under the same I : E ratio, the effects of inspiratory pause on mean airway pressure and gas exchange are not certain. Moreover, the effects may be different according to the resistance of respiratory system. So we studied the effects of inspiratory pause on airway pressure and gas exchange under the same I : E ratio in volume-controlled ventilation. Methods: Airway pressure and arterial blood gases were evaluated in 12 patients under volume-controlled mechanical ventilation with and without inspiratory pause time 5%. The I : E ratio of 1 : 3, $FiO_2$, tidal volume, respiratory rate, and PEEP were kept constant. Results: $PaCO_2$ with inspiratory pause was lower than without inspiratory pause ($38.6{\pm}7.4$ mmHg vs. $41.0{\pm}7.7$ mmHg. p<0.01). P(A-a)$O_2$ was not different between ventilation with and without inspiratory pause $185.3{\pm}86.5$ mmHg vs. $184.9{\pm}84.9$ mmHg, p=0.766). Mean airway pressure with inspiratory pause was higher than without inspiratory pause ($9.7{\pm}4.0\;cmH_2O$ vs. $8.8{\pm}4.0\;cmH_2O$, p<0.01). The resistance of respiratory system inversely correlated with the pressure difference between plateau pressure with pause and peak inspiratory pressure without pause (r=-0.777, p<0.l), but positively correlated with the pressure difference between peak inspiratory pressure with pause and peak inspiratory pressure without pause (r=0.811, p<0.01). Thus the amount of increase in mean airway pressure with pause positively correlated with the resistance of respiratory system (r=0.681, p<0.05). However, the change of mean airway pressure did not correlated with the change of $PaCO_2$. Conclusion: In volume-controlled ventilation under the same I : E ratio of 1 : 3, inspiratory pause time of 5% increases mean airway pressure and improves ventilation. Although the higher resistance of respiratory system, the more increased mean airway pressure, the increase in mean airway pressure did not correlated with the change in $PaCO_2$.

      • KCI등재
      • SCOPUSKCI등재

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