Showing papers by "Huan Guo published in 2010"
National Health Research Institutes1, National Institutes of Health2, Seoul National University3, National Taiwan University4, Academia Sinica5, International Agency for Research on Cancer6, Peking Union Medical College7, Vanderbilt University8, National Chung Hsing University9, China Medical University (Taiwan)10, Huazhong University of Science and Technology11, Kyungpook National University12, Korea University13, Nanjing Medical University14, National University of Singapore15, Chang Gung University16, Kaohsiung Medical University17, National Cheng Kung University18, National Yang-Ming University19, Inha University20
TL;DR: 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.
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 27 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=1.30610 211 ). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p=5.38610 211 ). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p=2.60610 220 , 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 CLPTM1LTERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
210 citations
TL;DR: Wang et al. as mentioned in this paper found that the -1271C allele was associated with a significantly increased lung cancer risk in the two independent patient case-control studies (P C variant may affect lung cancer susceptibility and survival by modulating endogenous Hsp27 synthesis levels).
Abstract: PURPOSE Heat-shock protein 27 (Hsp27), encoded by HSPB1, plays crucial roles in tumorigenesis and cell survival and is reported to be an independent prognosis marker for cancer. We hypothesized that genetic variants of the HSPB1 gene may be associated with lung cancer susceptibility and survival. PATIENTS AND METHODS We first resequenced the full-length HSPB1 gene and then genotyped three selected tag single nucleotide polymorphisms (SNPs) in 1,152 paired Chinese lung cancer patient cases and controls. Another 500 paired patient cases and controls were used for replication. We also evaluated the roles of these tagSNPs in the overall survival of 248 patients with advanced non-small-cell lung cancer (NSCLC), and validated the results in another 335 patients with advanced NSCLC. The genotype-phenotype correlation was assessed in 309 workers with occupational exposure to polycyclic-aromatic hydrocarbons (PAHs) as well as by luciferase reporter assay and Western blotting analysis. RESULTS The -1271C allele was associated with a significantly increased lung cancer risk in the two independent patient case-control studies (P C variant may affect lung cancer susceptibility and survival by modulating endogenous Hsp27 synthesis levels.
39 citations
TL;DR: Findings suggest that genetic variants in HSPA8 gene (especially promoter SNP rs2236659) contribute to the CHD susceptibility by affecting its expression level.
Abstract: Background
There is ample evidence that Hsp70 takes part in the progress of coronary heart disease (CHD). This implies that genetic variants of Hsp70 genes such as HSPA8 (HSC70) gene might contribute to the development of CHD. The present study aimed to investigate whether certain genetic variants of HSPA8 gene are associated with CHD in Han Chinese people.
30 citations
TL;DR: The results suggested that genetic variations in key NER genes, especially in XPA and XPC genes, may modulate DNA damage levels when exposed to PAHs.
Abstract: We explored the effects of single nucleotide polymorphisms (SNP) of nucleotide excision repair (NER) genes on DNA damage caused by exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH) in 475 Chinese workers. We quantified urinary 1-hydroxypyrene using high-performance liquid chromatography, and the DNA damage level of lymphocytes was examined by the comet assay and represented as the Olive tail moment (OTM) value. We genotyped 38 tagSNPs in 10 NER genes. The SNP function was further investigated using luciferase reporter assay in three cell lines. Our results showed that two promoter SNPs, XPA rs1800975 and XPC rs3731055, were associated with lower OTM values (P(trend) = 0.01 and 0.02 respectively). However, another missense SNP rs2228001 in the XPC gene was positively associated with OTM value (P(trend) = 0.01). A stratified analysis found that the association between this SNP and DNA damage was only observed among subjects with higher PAH exposure levels but not among those with lower exposure levels (P(interaction) = 0.018). A dose-response association was found between the combined risk alleles of the above three genetic variants and increased DNA damage levels (P(trend) = 0.004). This association was more pronounced in subjects with higher PAH exposure than those with lower exposure levels (P(interaction) = 0.046). Our functional study indicated that XPA rs1800975G and XPC rs3731055A alleles had a higher luciferase expression than their corresponding SNP alleles (P < 0.05). These results suggested that genetic variations in key NER genes, especially in XPA and XPC genes, may modulate DNA damage levels when exposed to PAHs.
26 citations
22 Feb 2010-Journal of Environmental Science and Health Part A-toxic\/hazardous Substances & Environmental Engineering
TL;DR: Although the increased MNed BNC frequencies among the exposed group may be associated with the co-exposure of various chemical pollutants in the environment, there was no statistical evidence of an association between GSTs genotypes and frequencies of micronuclei in the study population.
Abstract: In the present study, we investigated whether genetic polymorphisms of metabolic enzymes in an exposed population were associated with genotoxic effects of the pollutants from e-waste in 58 subjects (the exposed) resided in a typical e-waste recycling site and 80 subjects (the controls) from a village away from the recycling site Effects of genetic polymorphisms of glutathione S-transferases (GSTs) (GSTT1 and GSTM1) on the frequency of micronucleated binucleated cells (MNed BNC) in peripheral blood lymphocytes were evaluated GSTM1 and GSTT1 were typed using PCR-restriction fragment length polymorphism methods Cytogenetic alterations were evaluated using the cytokinesis-block micronucleus assay The MNed BNC frequency was significantly higher in the exposed group (median: 40‰, IQR: 20–70‰) than in the control group (median: 10‰, IQR: 00–20‰, P < 001 for both comparisons); sera GST activities were also higher in the exposed subjects with either non-null GSTT1 (mean ± SD: 2027 ± 643) or non-null
26 citations