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David C Christiani

Publications and source records attributed to David C Christiani.

At least 55 records · Page 3Linked to original sources
PubMed2005

Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer.

Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been associated with higher risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and low expression of ERCC1 mRNA levels has been associated with higher risk of cancers. We examined the association between two polymorphisms of ERCC1, 8092C > A (rs3212986) and 19007T > C (codon 118, rs11615), which are associated with altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer patients and 1,358 controls. The results were analyzed using logistic regression models, adjusting for relevant covariates. The two polymorphisms were in Hardy-Weinberg disequilibrium and in linkage disequilibrium. There was no overall association between ERCC1 polymorphisms and lung cancer risk, with the adjusted odds ratios (AOR) of 1.26 [95% confidence interval (95% CI), 0.81-1.96] for the 8092C > A polymorphism (A/A versus C/C) and 0.93 (95% CI, 0.67-1.30) for the 19007T > C polymorphism (C/C versus T/T). Stratified analyses revealed that the AORs for the 8092C > A polymorphism (A/A versus C/C) decreased significantly as pack-years increased, with the AOR of 2.11 (95% CI, 1.03-4.31) in never smokers and 0.50 (95% CI, 0.25-1.01) in heavy smokers (>/=56 pack-years), respectively. Consistent results were found when gene-smoking interaction was incorporated by joint effects and interactions models that considered both discrete and continuous variables for cumulative smoking exposure. The same direction for the gene-smoking interaction was found for the 19007T > C polymorphism, although the interaction was not statistically significant. In conclusion, ERCC1 8092C > A polymorphism may modify the associations between cumulative cigarette smoking and lung cancer risk.

Adult↗
PubMed2005

Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water.

Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (As(in)) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 mug As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dose-dependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (beta = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (beta = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between As(in) exposure and toenail As(in) content.

Adolescent↗
PubMed2005

Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients.

Vitamin D may inhibit the development and progression of a wide spectrum of cancers. We investigated the associations of surgery season and vitamin D intake with recurrence-free survival (RFS) and overall survival in 456 early-stage non-small cell lung cancer patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median (range) follow-up time was 71 (0.1-140) months, with 161 recurrence and 231 deaths. Patients who had surgery in summer had a better RFS than those who had surgery in winter (adjusted hazard ratio, 0.75; 95% confidence interval, 0.56-1.01), with 5-year RFS rates of 53% (45-61%) and 40% (32-49%), respectively (P = 0.10, log-rank test). Similar association between surgery season and RFS was found among the 321 patients with dietary information (P = 0.33, log-rank test). There was no statistically significant association between vitamin D intake and RFS. Because both season and vitamin D intake are important predictors for vitamin D levels, we investigated the joint effects of surgery season and vitamin D intake. Patients who had surgery during summer with the highest vitamin D intake had better RFS (adjusted hazard ratio, 0.33; 95% confidence interval, 0.15-0.74) than patients who had surgery during winter with the lowest vitamin D intake, with the 5-year RFS rates of 56% (34-78%) and 23% (4-42%), respectively. Similar associations of surgery season and vitamin D intake with overall survival were also observed. In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients.

Adult↗
PubMed2005

Case report: occupationally related recurrent varicella (chickenpox) in a hospital nurse.

Commonly accepted outcomes of varicella-zoster virus (VZV) infections include chickenpox (primary) and shingles (recurrence or latency), as well lifetime immunity against chickenpox. We report the case of a registered nurse who worked in a neurologic surgery ward in a general hospital in Taipei, Taiwan. While working there for approximately 1 year, she developed recurrent chickenpox after caring for a paraparesis patient, who had herpes zoster during hospitalization in August 2002. The varicella incubation period was 10 days, which matched the range (10-21 days). Recently negative specific serum IgM and positive specific serum IgG indicated a past VZV infection. The nurse did not get herpes zoster from the second episode of varicella on 9 August 2002 to 4 April 2005 and is now convalescing. We conclude that occupational VZV hazards exist in the health care environment and suggest testing for VZV antibody and a VZV vaccination program for susceptible health care workers. Key words: chickenpox, indirect fluroscent antibody, occupational exposure, polymerase chain reaction, shingles, Taiwan, varicella-zoster virus.

Adult↗
PubMed2005

Global gene expression profiling in whole-blood samples from individuals exposed to metal fumes.

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole-blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures.

Adult↗
PubMed2005

Seat inclination, use of lumbar support and low-back pain of taxi drivers.

OBJECTIVES: Epidemiologic evidence supporting optimal seating is limited and inconsistent. This cross-sectional study was conducted to examine the association between seat inclination, use of lumbar support, and the prevalence of clinically significant low-back pain among taxi drivers METHODS: A digital inclinometer was used to measure inclinations of seat surfaces (theta(seat)) and backrests (theta(back)), and calculate the back-to-thigh angle (theta(back-thigh)). Structured interviews were conducted to gather information on the use of lumbar support and the prevalence of low-back pain that had led to medical attention or absence from driving in the past month. A multiple logistic regression analysis was used to estimate the prevalence odds ratio (OR) with adjustment for age, body mass index, professional seniority, monthly driving hours, and the intensity of exposure to whole-body vibration. RESULTS: Among 224 drivers, the mean theta(seat), and theta(backrest) were 14.5 (SD 9.6) and 95.1 (SD 2.7) degrees, respectively, resulting in theta(back-thigh) of 80.6 (SD 9.3) degrees. Fifty-five percent used a lumbar support regularly, but 25% reportedly had significant low-back pain. The prevalence of low-back pain was 23% among those with theta(back-thigh) <86 degrees, 37% for those with a theta(back-thigh) of 86 approximately 91 degrees, and 9% for a theta(back-thigh) of >91 degrees. The adjusted OR comparing those with a theta(back-thigh) of < or = 91 degrees to those with a theta(back-thigh) of >91 degrees was 5.11 [95% confidence interval (95% CI) 1.07 approximately 24.4]. For regularly using drivers versus those not using lumbar support, the prevalence of low-back pain was 18% versus 34%, with an adjusted OR of 0.33 (95% CI 0.16 approximately 0.68). Neither theta(seat) nor theta(backrest) alone was significantly associated with low-back pain. CONCLUSIONS: The epidemiologic observation of this study was consistent with the results of prior biomechanical studies on appropriate seat inclinations and the use of lumbar support. Prospective studies are needed to confirm the true beneficial effects of these seating parameters.

Automobile Driving↗
PubMed2004

The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms.

BACKGROUND: Exogenous reactive oxygen species (ROS) induces DNA damage. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals, a major type of ROS, into hydrogen peroxide. p53 is a tumor suppressor gene, and X-ray cross-complementing group 1 (XRCC1) is involved in the base-excision repair of ROS-induced DNA damage. METHODS: The authors investigated whether the SOD2 Ala16Val polymorphism modifies the associations between p53 Arg72Pro and XRCC1 Arg399Gln polymorphisms and the risk of nonsmall cell lung carcinoma (NSCLC) in a case-control study of 935 Caucasian patients with NSCLC and 1233 healthy control participants. The results were analyzed using logistic regression models that were adjusted for possible confounding variables. RESULTS: There was no association between p53 or XRCC1 polymorphism and NSCLC risk for individuals with SOD2 Ala/Ala or Ala/Val genotype. For individuals with the SOD2 Val/Val genotype, greater risks were found in association with p53 (variant Pro allele vs. Arg/Arg), XRCC1 (variant Gln allele vs. Arg/Arg), and the combination of the two polymorphisms ("double variant" vs. "double wild type"), with the adjusted odds ratios (ORs) of 1.84 (95% confidence interval [95% CI], 1.20-2.82), 1.39 (95% CI, 0.98-2.21), and 2.54 (95% CI, 1.38-4.68), respectively. Furthermore, the greater risk for the double variant of p53 and XRCC1 in the SOD2 Val/Val genotype group was specific only for patients with adenocarcinoma and not for patients with squamous cell carcinoma, with adjusted ORs of 3.31 (95% CI, 1.68-6.51) and 0.69 (95% CI, 0.24-2.02), respectively. CONCLUSIONS: The SOD2 Val/Val genotype may increase the risk of NSCLC carried by XRCC1 and p53 polymorphisms, particularly for adenocarcinoma.

Adult↗
PubMed2004

Microsomal epoxide hydrolase, endotoxin, and lung function decline in cotton textile workers.

Occupational exposure to endotoxin in organic dust may induce lung function decline. Microsomal epoxide hydrolase (mEH) detoxifies reactive oxygen species generated by endotoxin exposure, and polymorphisms of the mEH gene are associated with altered enzyme activity. We investigated the associations between mEH polymorphisms, endotoxin exposure, and lung function decline in a 20-year prospective study of 265 workers exposed to endotoxin and 234 control subjects. mEH Tyr113His and His139Arg polymorphisms were genotyped by the 5' nuclease assay, and data were analyzed using multivariate linear regression models, adjusting for important covariates. Overall, the annual decline rate of FEV1 was 29.47 ml during the 20-year follow-up. Endotoxin exposure was associated with faster lung function decline among genotypes associated with slower enzyme activity: estimates (SE) of annual FEV1 decline rates for endotoxin exposure were -2.33 (2.07), -2.81 (1.66), and -6.73 (2.83) ml for Tyr/Tyr, Tyr/His, and His/His genotype groups, respectively, for the Tyr113His polymorphism; and -1.82 (2.58) and -4.27 (1.33) ml for Arg/Arg + His/Arg and His/His genotypes, respectively, for the His139Arg polymorphism. We conclude that mEH polymorphisms modify the association between occupational endotoxin exposure and longitudinal lung function decline.

Case-Control Studies↗
PubMed2004

MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma.

Manganese superoxide dismutase (SOD2) and myeloperoxidase (MPO) are polymorphic enzymes involved in reactive oxidative species metabolism. In this case-control study (830 non-small cell lung carcinoma (NSCLC) patients; 1119 controls) we evaluated whether the MPO -G463A polymorphism (associated with a novel estrogen receptor binding site) modifies the association between the SOD2 Ala16Val polymorphism and NSCLC risk differently by gender. For women carrying the MPO variant genotypes, the adjusted odds ratio of the SOD2 polymorphism (Val/Val vs. Ala/Ala) was 3.26 (95% CI, 1.55-6.83). No associations were found in men or in women carrying the MPO GG wildtype genotype.

Adult↗
PubMed2004

Lung adenocarcinoma and human papillomavirus infection.

Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation.

Adenocarcinoma↗
PubMed2004

Genetic susceptibility to tobacco-related cancer.

Although cigarette smoking is the dominant risk factor for several epithelial cancers, only a small fraction of individuals with tobacco exposure develop cancer. The underlying hypothesis is that genetic factors may render certain smokers more susceptible to cancer than others. Genetic alterations in critical regulatory pathways may predispose cells to carcinogenesis. These pathways include regulation of xenobiotic metabolism; control of genomic stability, including DNA repair mechanisms, cell-cycle checkpoints, apoptosis and telomere length; and control of microenvironmental factors, such as matrix metalloproteinases, inflammation and growth factors. In addition, epigenetic events, such as promoter hypermethylation and loss of imprinting, are also involved in carcinogenesis. In this review, we will summarize recent advances in genetic susceptibility to tobacco-related cancer. Emphasizing on risk assessment, we will describe how genetic variations in the above-mentioned genetic pathways modify the tobacco-related cancer risk. In addition, we will discuss how genetic variations may assist in predicting clinical outcome, such as the natural history of cancer and treatment response. The measurements of genetic susceptibility by both genotypic and phenotypic assays are covered in the text. Finally, we present a number of current concerns that need to be addressed as the exciting field of molecular cancer epidemiology advances rapidly.

Cytochrome P-450 Enzyme System↗
PubMed2004

Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

DNA repair is a critical mechanism of resistance to platinum-based chemotherapy. Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Increased ERCC1 mRNA levels are related directly to platinum resistance in various cancers. We examined the association between two polymorphisms of ERCC1, codon 118 C/T and C8092A, which are associated with altered ERCC1 mRNA levels and mRNA stability, and overall survival (OS) in 128 advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. The two polymorphisms were in linkage disequilibrium. There was a statistically significant association between the C8092A polymorphism and OS (P = 0.006, by log-rank test), with median survival times of 22.3 (C/C) and 13.4 (C/A or A/A) months, respectively, suggesting that any copies of the A allele were associated with poor outcome. No statistically significant association was found for the codon 118 polymorphism and OS (P = 0.41, by log-rank test), with median survival times of 19.9 (T/T), 16.1 (C/T), and 13.3 (C/C) months, respectively. In conclusion, the ERCC1 C8092A polymorphism may be a useful predictor of OS in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

Adult↗
PubMed2004

The role of collagen IX tryptophan polymorphisms in symptomatic intervertebral disc disease in Southern European patients.

STUDY DESIGN: We conducted a cross-sectional, genotyping study of intervertebral disc disease patients and controls. OBJECTIVES: To determine the contribution of COL9A2 and COL9A3 Tryptophan polymorphisms to intervertebral disc disease development in a genetically heterogeneous, Southern European population compared to previous Finnish studies. SUMMARY OF BACKGROUND DATA: The COL9A2 and COL9A3 genes encode the alpha2 and alpha3 chains of Collagen IX. Recent Finnish studies suggest that a tryptophan polymorphism in the COL9A2 gene (Trp2) results in hereditary intervertebral disc disease, whereas a similar tryptophan mutation in COL9A3 (Trp3) conveys a 3-fold risk of intervertebral disc disease. METHODS: We studied 105 symptomatic patients with radiographically and/or surgically proven lumbar (98%, n = 103) or cervical (2%, n = 2) intervertebral disc disease and 102 age-matched controls without spinal complaints from hospitals in Athens, Greece. Intervertebral disc disease was defined as significant disc herniation resulting in persistent back or leg pain. We genotyped all patients for COL9A2 and COL9A3 allele variations using a polymerase chain reaction-based technique. RESULTS: None of our patients had the Trp2 allele. Consistent with previous Finnish findings, more Greek intervertebral disc disease cases (8.6%) than controls (4.9%) had at least 1 Trp3 allele, but this difference did not reach statistical significance (P = 0.293). The allele frequency of the Trp3 mutation was significantly higher among previously studied Finnish patients with intervertebral disc disease (12.3%) than among the Southern European patients with intervertebral disc disease in our study (4.3%), P = 0.001. CONCLUSIONS: The differences in Trp allele frequency we found between Greek and Finnish patients with intervertebral disc disease most likely represent true differences in polymorphism prevalence between the respective populations. The 2 previously described Trp alleles in COL9A2 and COL9A3 are likely to be less significant susceptibility factors for intervertebral disc disease development in Southern European populations.

Adult↗
PubMed2004

XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy.

PURPOSE: Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of DNA repair genes are associated with differential DNA repair activity and may explain interindividual differences in overall survival after therapy with platinum agents for non-small-cell lung cancer (NSCLC). METHODS: We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes in 103 patients with stage III (54%) and IV (46%) NSCLC treated with platinum-based chemotherapy. RESULTS: Median age was 58 years (range, 32 to 77 years), 49% were females, and there were 86 deaths. Median follow-up period was 61.9 months. Median survival time (MST) was 14.9 months; by stage, MST was 28.6 months (IIIA), 16.0 months (IIIB), and 9.3 months (IV). Genotypes were not associated with stage. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival (P =.003 and P =.07, respectively, by log-rank test). Similarly, when we compared combinations of variant alleles across both polymorphisms, we found that a greater number of variant alleles was associated with decreasing overall survival (P =.009, log-rank test). These polymorphisms independently predicted overall survival even after taking into account stage, performance status, and chemotherapy regimen. CONCLUSION: Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in platinum-treated patients with advanced NSCLC.

Adult↗
PubMed2004

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

BACKGROUND: Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS: We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. RESULTS: Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. CONCLUSIONS: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

Adenocarcinoma↗
PubMed2004

High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines.

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to single-nucleotide polymorphism (SNP) arrays is an efficient method to detect genome-wide cancer LOH. Here, we survey LOH patterns in a panel of 33 human lung cancer cell lines using SNP array hybridization containing 1500 SNPs. We compared the LOH patterns generated by SNP array hybridization to those previously obtained by 399 microsatellite markers and find a high degree of concordance between the two methods. A novel informatics platform, dChipSNP, was used to perform hierarchical tumor clustering based on genome-wide LOH patterns. We demonstrate that this method can separate non-small-cell and small-cell lung cancer samples based on their shared LOH. Furthermore, we analysed seven human lung cancer cell lines using a novel 10 000 SNP array and demonstrate that this is an efficient and reliable method of high-density allelotyping. Using this array, we identified small regions of LOH that were not detected by lower density SNP arrays or by standard microsatellite marker panels.

Biomarkers, Tumor↗