• Tuberculosis and Respiratory Diseases
• /
• v.71 no.5
• /
• pp.349-354
• /
• 2011

Background: Lung cancer is the leading cause of cancer deaths in the world. Human papillomavirus (HPV) infection and E6 oncoprotein expression are known risk factors for the development of non-small cell lung cancer (NSCLC). This study was performed to evaluate the prevalence of HPV 16/18 E6 oncoprotein expression in patients with NSCLC. Methods: Immunohistochemical stains of the HPV 16/18 E6 oncoprotein were performed in tumor tissues from 68 patients with NSCLC who underwent curative surgery from March 2006 to November 2008. Results: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC and a statistical analysis revealed that E6 oncoprotein expression was significantly higher in females (p=0.028), never smokers (p=0.045), and patients with adenocarcinoma (p=0.022) than that in other patients. Conclusion: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC. Further studies detecting HPV infection and E6 oncoprotein expression in never smoking patients with NSCLC are needed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.4063-4070
• /
• 2016

Background: Cytochrome P450 2E1 (CYP2E1) and catechol-O-methyltransferase (COMT) genes may contribute to susceptibility to lung cancer because of their critical involvement in mechanisms of carcinogenesis. Materials and Methods: We evaluated the role of CYP2E1 rs2031920 and COMT rs4680 in a case-control study involving 462 lung cancer cases and 379 controls in Japanese. Logistic regression was used to assess adjusted odds ratios (OR) and 95% confidence intervals (CI). Multiplicative and additive interactions with cigarette smoking or alcohol use were also examined. Results: Neither CYP2E1 rs2031920 nor COMT rs4680 was associated with lung cancer risk overall. However, smokers with the CC genotype of CYP2E1 rs2031920 (OR = 3.57, 95% CI = 2.26 - 5.63) presented a higher risk of lung cancer than those with at least one T allele (OR = 2.91, 95% CI = 1.70 - 4.98) as compared to never-smokers with at least one T allele (reference). Subjects with excessive drinking and the CC genotype of CYP2E1 rs2031920 had a significantly higher risk (OR = 2.22, 95% CI =1.39 - 3.56) than appropriate drinkers with at least one T allele. A similar tendency was observed between COMT rs4680 and either smoking or drinking habits. There were no multiplicative or additive interactions between the polymorphisms and either smoking or alcohol use. Conclusions: Our findings indicate that CYP2E1 rs2031920 and COMT rs4680 are not major contributors to lung cancer risk in our Japanese population. Future studies on the genetics of lung cancer in Japanese and their environment interactions are required.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.321-326
• /
• 2014

Background: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. Materials and Methods: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. Results: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94-18.17; p=0.002). Conclusions: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.6
• /
• pp.2827-2832
• /
• 2016

Purpose: To estimate the number of deaths attributable to second hand smoking (SHS) in Morocco in 2012. Materials and Methods: prevalence based study focusing on mortality from ischaemic heart disease (IHD) and lung cancer among non-smokers aged 35 and over. Prevalence of SHS among never smokers was gathered from a national cross sectional survey on tobacco and population attributable risk (PAR) was calculated by applying PARs to mortality. The analyses were stratified by sex, age and area of exposure. Results: Rates for exposure to SHS among men aged 35-64 years ranged from 20.0% at home to 57.4% at work. Among non-smoking Moroccans aged 35 and over, 233 (IC: 147 - 246) deaths were attributable to exposure to SHS; 156 (IC: 100 - 221) in women and 77 (IC: 44 -125) in men. A total of 173 (122 - 222) deaths were estimated to have been caused by exposure only at home, 34 (9 - 76) by exposure only at the work place and 26 (15 - 58) by exposure both at home and work places. Exposure to SHS could be responsible for 182 (128 - 237) deaths from IHD and 51 (19 - 109) from lung cancer. Conclusions: These data confirm that SHS needs urgent attention in Morocco.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5171-5174
• /
• 2013

Background: This study aimed to explore potential associations between single nucleotide polymorphisms (SNPs) of the x-ray repair cross-complementing group 1 (XRCC1) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) and non-small cell lung cancer (NSCLC) susceptibility in non-smoker Chinese patients. Methods: A total of 200 NSCLC patients and 200 healthy controls with matched age and gender were recruited for genotyping of XRCC1 SNPs (rs2256507 and rs1001581) and CLPTM1L SNPs (rs401681 and rs4975616). Association of these SNPs with NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. Results: The frequencies of genotype and allele in these four loci (rs2256507, rs1001581, rs401681, and rs4975616) were not significantly different between the cases and controls, or between either of the histological subgroups (adenocarcinoma and squamous cell carcinoma) and controls. Conclusions: Although these SNPs are associated with NSCLC risk in patients with a tobacco-smoking habit, this study demonstrated that XRCC1 and CLPTM1L gene SPNs are not linked with NSCLC risk in non-smoking patients, indicating that molecular mechanisms of NSCLC betwee tobacco smokers and non-smokers may be different. Future studies are needed to uncover the underlying molecular mechanisms for NSCLC in non-smokers.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2643-2647
• /
• 2013

Background: Despite anti-smoking campaigns, smoking prevalence among Thai males aged 30 or older is high, at around 50%. The purpose of this study was to determine the relationship between smoking and mortality in a rural Thai community. Materials and Methods: Subjects enrolled into the Khon Kaen cohort study between 1990 and 2001 were followed up for their vital status until $16^{th}$ March 2012. The death resource was from the Bureau of Policy and Strategy, Ministry of Interior, Thailand. A Cox proportional hazards model was used to analyse the association between smoking and death, controlling for age, education level and alcohol drinking, and confidence intervals were calculated using the floating risk method. Results: The study recruited 5,962 male subjects, of whom 1,396 died during a median 13.5 years of follow-up. Current smokers were more likely to die than never smokers after controlling for age, education level and alcohol drinking (HR, 95%CI: 1.41, 1.32-1.51), and the excess mortality was greatest for lung cancer (HR, 95%CI: 3.51, 2.65-4.66). However, there was no increased risk with increasing dose of tobacco, and no difference in risk between smokers of yamuan (hand-rolled cigarettes) and manufactured tobacco. Conclusion: Mortality from cancer, particularly lung cancer, and from all causes combined is dependent on smoking status among men in rural Thailand, but the relative risks are lower than have been reported from studies in high income countries, where the tobacco epidemic is more established.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.9
• /
• pp.3927-3932
• /
• 2014

Background: Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. Patients and Methods: EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. Results: EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5ng/ml seemed to be higher than patients with a concentration over 5ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. Conclusions: The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

• Journal of Radiation Protection and Research
• /
• v.40 no.3
• /
• pp.155-161
• /
• 2015

Radon is a naturally occurring radioactive gas and a major indoor contribution of exposure to ionizing radiation in dwellings. $^{222}Rn$ is a health hazard gas what is responsible for thousand lung cancer deaths every year. In this study, indoor radon concentrations present in thirty representative houses in Mahallat city, Iran, were determined in order to estimate lung cancer risk associated with residential radon exposure. Long-term passive method, using CR-39, was used to measure the radon concentration. The results showed an association between the age of the dwellings and the indoor radon concentration that was found, in that the concentration of radon tended to increase as the age of the dwelling also increased. The indoor radon concentrations were calculated to be within the range of $23{\pm}2$ to $350{\pm}26Bq{\cdot}m^{-3}$, with an average of $158Bq{\cdot}m^{-3}$. The annual effective dose from inhaled radon and its decay products was calculated between $0.8{\pm}0.1$ and $12.3{\pm}0.9mSv{\cdot}y^{-1}$, with an average of $5.5mSv{\cdot}y^{-1}$. By taking into consideration the EPA recommendation and ICRP statement, the average annual risk of lung cancer from inhaled radon was calculated as 0.09%, 0.06%, 0.01%, and 0.03% for current smokers (CS), those who had ever smoked (ES), never smokers (NS) and the general population, respectively.

• Journal of Preventive Medicine and Public Health
• /
• v.53 no.6
• /
• pp.476-486
• /
• 2020

Objectives: The objective of this study was to estimate the risk of lung cancer in relation to angiotensin II receptor blocker (ARB) use among patients with hypertension from the Korean National Health Insurance Service-National Health Screening Cohort. Methods: We conducted a retrospective cohort study of patients with hypertension who started to take antihypertensive medications and had a treatment period of at least 6 months. We calculated the weighted hazard ratios (HRs) and their 95% confidence intervals (CIs) of lung cancer associated with ARB use compared with calcium channel blocker (CCB) use using inverse probability treatment weighting. Results: Among a total of 60 469 subjects with a median follow-up time of 7.8 years, 476 cases of lung cancer were identified. ARB use had a protective effect on lung cancer compared with CCB use (HR, 0.75; 95% CI, 0.59 to 0.96). Consistent findings were found in analyses considering patients who changed or discontinued their medication (HR, 0.50; 95% CI, 0.32 to 0.77), as well as for women (HR, 0.56; 95% CI, 0.34 to 0.93), patients without chronic obstructive pulmonary disease (HR, 0.75; 95% CI, 0.56 to 1.00), never-smokers (HR, 0.64; 95% CI, 0.42 to 0.99), and non-drinkers (HR, 0.69; 95% CI, 0.49 to 0.97). In analyses with different comparison antihypertensive medications, the overall protective effects of ARBs on lung cancer risk remained consistent. Conclusions: The results of the present study suggest that ARBs could decrease the risk of lung cancer. More evidence is needed to establish the causal effect of ARBs on the incidence of lung cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.5
• /
• pp.490-497
• /
• 2005

Background : The paraoxonase enzyme plays a significant role in the detoxification of various organophosphorous compounds in mammals, and paraoxonase (PON) 1 is one of the endogenous free-radical scavenging systems in the human body. In this study, we investigated the interaction between cigarette smoking and the genetic polymorphism of PON1 with lung cancer in Korean males. Methods : Three hundred thirty five patients with lung cancer and an equal number of age-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and alcohol drinking habits. A 5' exonuclease assay (TaqMan) was used to genotype the PON1 Q192R polymorphism. The effects of smoking habits and drinking habits, the PON1 Q192R polymorphism and their interactions were statistically analyzed. Results : Cigarette smoking and the Q/Q genotype of PON1 were significant risk factors for lung cancer. Individuals carrying the Q/Q genotype of PON1 were at a higher risk for lung cancer as compared with those individuals carrying the Q/R or R/R genotype (odds ratio, 2.84; 95% confidence interval, 1.69 - 4.79). When the groups were further stratified by the smoking status, the Q/Q PON1 was associated with lung cancer among the current or ex-smokers (odds ratio, 2.56; 95% confidence interval, 1.52 - 4.31). Current smokers or ex-smokers who had the Q/Q genotype showed an elevated risk for lung cancer (odds ratio: 15.50, 95% confidence interval: 6.76 - 35.54) as compared with the group of subjects who never smoked, and had the Q/R or R/R genotype. The odds ratios (95% confidence interval) of smokers with the PON1 Q/Q type compared to the nonsmokers with the PON1 Q/R or R/R type were 53.77 (6.55 - 441.14) for squamous cell carcinoma, 6.25 (1.38 - 28.32) for adenocarcinoma, and 59.94 (4.66 - 770.39) for small cell carcinoma, and these results were statistically significant. Conclusion : These results suggest that cigarette smoking and the PON1 Q/Q genotype are risk factors for lung cancer. The combination of cigarette smoking and the PON1 Q/Q genotype significantly increased the lung cancer risk irrespective of the histologic type of cancer.