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Chin Hao Chang,
Chin Fu Hsiao,
Yu Min Yeh,
Gee Chen Chang,
Ying Huang Tsai,
Yuh Min Chen,
Ming Shyan Huang,
Hui Ling Chen,
Yao Jen Li,
Pan Chyr Yang,
Chien Jen Chen,
Chao A Hsiung,
Wu Chou Su
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ABSTRACT: Lung cancer is the leading cause of cancer death worldwide as well as in Taiwan. Interleukin-6 (IL-6) is a multifunctional cytokine and has been implicated in tumor progression. The present study recruited 245 patients with advanced (Stage 3B/4) non-small cell lung cancer (NSCLC) that had received chemotherapy, to evaluate associations between IL-6 and lung cancer-specific survival. Among these subjects, 112 gave blood samples before and 133 after the start of chemotherapy. Plasma IL-6 was measured using an enzyme linked-immuno-sorbent assay. The 33rd and 66th percentiles of IL-6 concentrations were 2.01 and 25.16 for the 245 patients, and were defined as the cutoff points for dividing the patients into low, intermediate, and high groups. Kaplan-Meier and Cox proportional-hazard models were used to evaluate the relationship between the IL-6 level and survival time. Results after adjusting for age, sex, smoking history, histologic type, and stage of lung cancer revealed a significant relationship. For all patients, the hazard ratio with high IL-6 levels for lung cancer-specific survival was 2.10 (95% confidence interval (CI)= 1.49-2.96) compared with low IL-6 levels. The hazard ratio for patients who were recruited before and after the start of chemotherapy was1.25 (95% CI= 0.73-2.13) and 3.66 (95% CI= 2.18-6.15), respectively. Patients with high circulating IL-6 also responded poorly to chemotherapy. Therefore, a high level of circulating IL-6 was associated with an inferior response and survival outcome in NSCLC patients treated with chemotherapy. © 2012 Wiley Periodicals, Inc.
International Journal of Cancer 10/2012; · 5.44 Impact Factor
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Yen-Li Lo,
Chin-Fu Hsiao,
Gee-Chen Chang,
Ying-Huang Tsai,
Ming-Shyan Huang,
Wu-Chou Su,
Yuh-Min Chen,
Che-Wei Hsin, Chin-Hao Chang,
Pan-Chyr Yang,
Chien-Jen Chen,
Chao A Hsiung
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ABSTRACT: OBJECTIVE: Lung cancers that occur in never smokers differ from those that occur in smokers. We performed an analysis of potential epidemiological risk factors for lung cancer among never smokers. METHODS: In this hospital-based matched case-control study, all 1,540 matched case-control pairs were Han Chinese in Taiwan. The data on demographic characteristics, smoking habit, exposure to environmental tobacco smoke, medical history of lung diseases, family history of lung cancer, and female characteristics were collected from a structured questionnaire. A multiple conditional logistic regression was used to estimate odds ratios and 95 % confidence intervals after adjusting for possible confounders. RESULTS: Overall, several epidemiological factors of lung cancer in never smokers were different between males and females. For the female population, subjects who were exposed to environmental tobacco smoke (OR = 1.39, 95 % CI = 1.17-1.67) with a history of pulmonary tuberculosis and with family history of lung cancer in first-degree relatives (OR = 2.44, 95 % CI = 1.79-3.32) had higher risk of lung cancer, while subjects with a history of hormone replacement therapy and using fume extractors for those who cooked were protective. For the male population, only subjects with family history of lung cancer in first-degree relatives (OR = 2.77, 95 % CI = 1.53-5.01) were significantly associated with risk of lung cancer. CONCLUSION: This study provides insights about the epidemiological factors of lung cancer in never smokers, adding to existing evidence that family history of lung cancer and environmental tobacco smoke may moderate lung cancer risk.
Cancer Causes and Control 05/2012; · 2.88 Impact Factor
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Chao Agnes Hsiung,
Qing Lan,
Yun-Chul Hong,
Chien-Jen Chen,
H Dean Hosgood,
I-Shou Chang,
Nilanjan Chatterjee,
Paul Brennan,
Chen Wu,
Wei Zheng, [......],
Chih-Yi Chen,
Kun-Chieh Chen,
Shi-Yi Yang,
Chi-Yuan Hu,
Chung-Kai Chang,
Joseph F Fraumeni,
Stephen Chanock,
Pan-Chyr Yang,
Nathaniel Rothman,
Dongxin Lin
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ABSTRACT: Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
PLoS Genetics 08/2010; 6(8). · 8.69 Impact Factor
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Chin-Hao Chang,
Chin-Fu Hsiao,
Gee-Chen Chang,
Ying-Huang Tsai,
Yuh-Min Chen,
Ming-Shyan Huang,
Wu-Chou Su,
Wan-Shan Hsieh,
Pan-Chyr Yang,
Chien-Jen Chen,
Chao A Hsiung
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ABSTRACT: Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) plays an important role in repairing oxidative DNA damage induced by tobacco carcinogens. In this case-control study, the authors examined the interactive effect of hOGG1 gene polymorphisms and cigarette smoking on the risk of lung cancer in Taiwan. A total of 1,096 cases and 1,007 controls were enrolled from 6 medical centers in Taiwan during 2002-2004. hOGG1 Ser326Cys genetic polymorphisms were determined using the MassARRAY system (SEQUENOM, Inc., San Diego, California). Tobacco smoking history was obtained through personal interview according to a structured questionnaire. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. The odds of developing lung cancer for persons with the Cys/Cys genotype versus the Ser/Ser genotype were 1.11 (95% confidence interval (CI): 0.74, 1.65) for never smokers, 1.45 (95% CI: 0.74, 2.83) for moderate smokers, and 3.52 (95% CI: 1.54, 8.06) for heavy smokers. The P value for interaction in the logistic model was 0.01. The increased risk associated with the Cys/Cys genotype among heavy smokers remained statistically significant for various histologic types of lung cancer, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. The authors conclude that there was a noticeable modifying effect on the association between hOGG1 genotype and lung cancer risk by cigarette smoking status.
American journal of epidemiology 09/2009; 170(6):695-702. · 5.59 Impact Factor
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ABSTRACT: For a genetic study in which there are concordant and discordant sibpairs for a complex disease trait and the measurements of other endophenotypes/intermediate phenotypes for each of the individuals are also available, we describe an allele-sharing based multipoint linkage test that utilizes nonparametrically the additional endophenotypes/intermediate phenotypes. The usefulness of this method is evaluated in simulation studies, which show that the gain in power is influenced by not only the endophenotypic value but also the correlation between the diagnosis-based phenotype and the endophenotype. In addition to reporting p values, our method also provides an index C(E), derived from the coefficients of the weight function associated with the endophenotype in the proposed statistic, to indicate the relevance of a specific endophenotype/intermediate phenotype in the genetic study. The simulation study indicates that a larger power, in general, corresponds to a larger value of the index C(E). The index C(E) is thus suggested as a quantity to be used in the choice of endophenotypes in linkage study. Data from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) are used to illustrate the method.
Genetic Epidemiology 03/2006; 30(2):133-42. · 3.44 Impact Factor
