• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8287-8292
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• 2016

Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p=0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3 'UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 'UTR is more informative than TSER polymorphism in predicting increased risk.

• Tuberculosis and Respiratory Diseases
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• 제77권2호
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• pp.55-59
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• 2014

The US National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality and a 6.7% decrease in all-cause mortality. The NLST is the only trial showing positive results in a high-risk population, such as in patients with old age and heavy ever smokers. Lung cancer screening using a low-dose chest computed tomography might be beneficial for the high-risk group. However, there may also be potential adverse outcomes in terms of over diagnosis, bias and cost-effectiveness. Until now, lung cancer screening remains controversial. In this review, we wish to discuss the evolution of lung cancer screening and summarize existing evidences and recommendations.

• Genomics & Informatics
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• 제19권1호
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• pp.3.1-3.12
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• 2021

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer-associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type-specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer-associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1123-1130
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• 2018

Purpose: Exposure to indoor radon is associated with lung cancer. This study aimed to estimate the number of lung cancer deaths attributable to indoor radon exposure, its burden of disease, and the effects of radon mitigation in Korea in 2010. Materials and Methods: Lung cancer deaths due to indoor radon exposure were estimated using exposure-response relations reported in previous studies. Years of life lost (YLLs) were calculated to quantify disease burden in relation to premature deaths. Mitigation effects were examined under scenarios in which all homes with indoor radon concentrations above a specified level were remediated below the level. Results: The estimated number of lung cancer deaths attributable to indoor radon exposure ranged from 1946 to 3863, accounting for 12.5-24.7% of 15623 total lung cancer deaths in 2010. YLLs due to premature deaths were estimated at 43140-101855 years (90-212 years per 100000 population). If all homes with radon levels above $148Bq/m^3$ are effectively remediated, 502-732 lung cancer deaths and 10972-18479 YLLs could be prevented. Conclusion: These findings suggest that indoor radon exposure contributes considerably to lung cancer, and that reducing indoor radon concentration would be helpful for decreasing the disease burden from lung cancer deaths.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.495-500
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• 2015

Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.

• Journal of Preventive Medicine and Public Health
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• 제40권3호
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• pp.233-238
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• 2007

Objectives : We aimed to assess the relationship between long-term exposure to air pollution and lung cancer in the Republic of Korea. Methods : Using the Annual Report of Ambient Air Quality in Korea, Annual Report of National Cancer Registration, and Annual Report on the Cause of Death Statistics, we calculated the standardized mortality ratio (SMR) and standardized incidence ratio (SIR) of lung cancer for both sexes in 74 areas from 7 Korean metropolitan cities. We performed random intercept, Poisson regression using empirical Bayes method. Results : Both SMRs and SIRs in the 7 metropolitan cities were higher in women than in men. Mean SIRs were 99.0 for males and 107.0 for females. The association between $PM_{10}$ and lung cancer risk differed according to gender. $PM_{10}$ was not associated with the risk of lung cancer in males, but both incidence and mortality of lung cancer were positively associated with $PM_{10}$ in females. The estimated percentage increases in the rate of female lung cancer mortality and incidence were 27% and 65% at the highest $PM_{10}$ category $({\geq}70\;{\mu}g/m^3)$, compared to the referent category $({\geq}50\;{\mu}g/m^3)$. Conclusions : Long-term exposure to $PM_{10}$ was significantly associated with female lung cancer incidence in 7 Korean metropolitan cities. Further study is undergoing to estimate the relative risk of $PM_{10}$ using multi-level analysis for controlling individual and regional confounders such as smoking and socioeconomic position.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4063-4070
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• 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
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• 제14권5호
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• pp.2801-2803
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• 2013

Background: The ABO blood groups and Rh factor may affect the risk of lung cancer. Materials and Methods: We analyzed 2,044 lung cancer patients with serologically confirmed ABO/Rh blood group. A group of 3,022,883 healthy blood donors of Turkish Red Crescent was identified as a control group. We compared the distributions of ABO/Rh blood group between them. Results: The median age was 62 years (range: 17-90). There was a clear male predominance (84% vs. 16%). Overall distributions of ABO blood groups were significantly different between patients and controls (p=0.01). There were also significant differences between patients and controls with respect to Rh positive vs. Rh negative (p=0.04) and O vs. non-O (p=0.002). There were no statistically significant differences of blood groups with respect to sex, age, or histology. Conclusions: In the study population, ABO blood types were associated with the lung cancer. Having non-O blood type and Rh-negative feature increased the risk of lung cancer. However, further prospective studies are necessary to define the mechanisms by which ABO blood type may influence the lung cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2877-2881
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• 2016

Background: Lung cancer is one of the most common causes of death that is rising in many countries including Iran. This study aimed to determine the impact of factors on survival of lung cancer patients at a referral center of lung diseases in Tehran, Iran. Materials and Methods: A retrospective study was conducted on adult lung cancer cases admitted to a referral center for lung diseases from 2011 to 2015. Multivariate analysis was performed to determine the risk factors for all-cause mortality. Results: Of a total 933 patients with lung cancer, 53.4% died, 49.3% of them at the hospital. Overall median follow-up time was 7 months. The most common histological type of cancer was adenocarcinoma with a 13 month median survival time. Age ${\geq}55$ and smoking remained significant for all-cause mortality on Cox analysis, whereas gender was not. Conclusions: The survival of lung cancer patients is poor and the patients with history of smoking and age${\geq}55$ are at increased risk of death. Having a large hospital-based registry provides a good measurement of prognostic statistics for lung cancer. Further investigations are necessary to establish reasons for mortality.

• Safety and Health at Work
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• 제7권3호
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• pp.251-255
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• 2016

Background: Building demolition can lead to emission of dust into the environment. Exposure to silica dust may be considered as an important hazard in these sites. The objectives of this research were to determine the amount of workers' exposure to crystalline silica dust and assess the relative risk of silicosis and the excess lifetime risk of mortality from lung cancer in demolition workers. Methods: Four sites in the Tehran megacity region were selected. Silica dust was collected using the National Institute for Occupational Safety and Health method 7601 and determined spectrophotometrically. The Mannetje et al and Rice et al models were chosen to examine the rate of silicosis-related mortality and the excess lifetime risk of mortality from lung cancer, respectively. Results: The amount of demolition workers' exposure was in the range of $0.085-0.185mg/m^3$. The range of relative risk of silicosis related mortality was increased from 1 in the workers with the lowest exposure level to 22.64/1,000 in the employees with high exposure level. The range of the excess lifetime risk of mortality from lung cancer was in the range of 32-60/1,000 exposed workers. Conclusion: Geometric and arithmetic mean of exposure was higher than threshold limit value for silica dust in all demolition sites. The risk of silicosis mortality for many demolition workers was higher than 1/1,000 (unacceptable level of risk). Estimating the lifetime lung cancer mortality showed a higher risk of mortality from lung cancer in building demolition workers.