Biomedical subjects

David C Christiani

Publications and source records attributed to David C Christiani.

At least 37 records · Page 2Linked to original sources

PubMed2006

Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients.

Our previous analysis suggested that surgery season in the summer time and high vitamin D intake are associated with improved survival in early-stage non-small cell lung cancer (NSCLC) patients. Here, we investigated the associations of vitamin D receptor (VDR) polymorphisms of Cdx-2 G>A, FokI C>T, and BsmI C>T with overall survival (OS) and recurrence-free survival (RFS) in 373 early-stage NSCLC patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median follow-up time was 71 months (range, 0.1-140 months), with 186 deaths and 127 recurrences. There was no association between VDR polymorphisms and survival, overall or among adenocarcinoma patients. Among squamous cell carcinoma (SCC) patients, the G/A+A/A genotype group of the Cdx-2 polymorphism was associated with better OS: the 5-year OS rates were 41% [95% confidence interval (95% CI), 28-53] for the G/G and 55% (95% CI, 39-71) for the G/A+A/A genotypes, respectively (P = 0.04, log-rank test), with the adjusted hazard ratio of 0.56 (95% CI, 0.33-0.95) for G/A+A/A versus G/G. For the joint effects of the three polymorphisms, subjects with two or more "protective" alleles have better OS among SCC patients, with the adjusted hazard ratios of 0.20 (95% CI, 0.09-0.48), 0.40 (95% CI, 0.19-0.87), and 0.43 (95% CI, 0.19-0.97), respectively, for subjects with two, three, and four or more "protective" alleles when compared with subjects with zero or one "protective" allele (P(trend) = 0.71). Similar associations were found in haplotype analysis and for RFS among SCC patients. In conclusion, VDR polymorphisms may be associated with improved survival among SCC patients of early-stage NSCLC.

Adult↗

PubMed2006

The impact of diet and betel nut use on skin lesions associated with drinking-water arsenic in Pabna, Bangladesh.

An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water samples were collected. Water samples were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR) = 1.67; 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68; 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41; 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89; 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded.

Adult↗

PubMed2005

Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer.

The MMPs (matrix metalloproteinases) are a family of secreted zinc metalloproteases that degrade the collagens of the extracellular matrix important in tissue remodeling and repair during development and inflammation. We investigated the associations between polymorphisms of MMP-1 (-1607 1G/2G, rs1799750), MMP-3 (-1171 5A/6A, rs3025058), and MMP-12 (-82AG, rs2276109, and 1082A/G, rs652438) and the risk of lung cancer in 2014 Caucasian lung cancer patients and 1323 healthy controls. The results were analyzed using logistic regression models, adjusting for covariates. The four polymorphisms were in Hardy-Weinberg disequilibrium. Except for the 1G-1082A, the other linkage disequilibrium tests between the four MMP polymorphisms were statistically significant (P < 0.001). There was no overall association between individual MMP polymorphism and the risk of lung cancer. The MMP polymorphisms jointly were associated with a non-statistically significant higher risk of lung cancer, with the adjusted odds ratio (AOR) of subjects with 5+ variant alleles versus zero variant allele of 1.31 [95% confidence interval (CI), 0.92-1.88]. Stronger associations were observed in never-smokers and males, with the corresponding AORs of 2.44 (95%CI, 1.10-5.43, P(trend) = 0.04) in never smokers and 1.35 (95%CI, 0.79-2.30, P(trend) = 0.04) in men. In haplotype analysis, the 1G-6A-82A-1082G haplotype was associated with higher risk of lung cancer among never smokers, with the AOR of 3.65 (95%CI, 1.62-8.20) when compared with the most common 1G-5A-82A-1082A haplotype. In conclusion, the combined MMP genotypes and associated haplotypes may be associated with higher risk of lung cancer, particularly among never smokers and men.

Adult↗

PubMed2005

Polyphenol associated-DNA adducts in lung and blood mononuclear cells from lung cancer patients.

The formation of smoking induced-DNA adducts is a critical factor in the induction of human lung cancer. As derivates of benzene and polyaromatic hydrocarbons (PAHs) are important compounds of tobacco smoke, in DNA isolated from human lung and blood mononuclear cells (MNCs) from 38 lung cancer patients, we used the (32)P-postlabeling assay to detect polyphenol associated DNA adducts. Two DNA adducts were detected in blood MNCs and lung tissue that co-chromatographed with DNA modifications from HL60 cells treated with combinations of benzene metabolites (e.g., hydroquinone and benzenetriol). These adducts were designated polyphenol-associated DNA adducts. Relative adduct levels for polyphenolic adducts were five-fold higher than aromatic adducts in both lung and MNCs. A significant correlation was observed between levels of polyphenol adducts and total duration of cigarette smoking in lung (r=0.34; P<0.04) and MNCs (r=0.7; P<0.04), but no correlation between levels of polyphenol adducts and pack-years consumption of cigarettes nor time since quitting smoking in former smokers. Long term former smokers and the one non-smoker in the study had detectable levels of polyphenol adducts. Surprisingly, the levels of polyphenol adducts in MNCs were highly correlated with aromatic adduct levels (r=0.84; P<0.001). Individual aromatic adducts in MNCs also correlated with polyphenol adducts. Total polyphenol adduct levels had a correlation with aromatic DNA adduct levels in lung tissue (r=0.46; P<0.01). To our knowledge these results are the only comparison of adducts in MNCs with lung tissue, and the only data set indicating that blood MNCs are a valid surrogate for lung adduct DNA burden.

Adenocarcinoma↗

PubMed2005

Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients.

PURPOSE: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity. EXPERIMENTAL DESIGN: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non-small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen. RESULTS: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03). CONCLUSIONS: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a >2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non-small cell lung cancer patients.

Adult↗

PubMed2005

Urinary metal and polycyclic aromatic hydrocarbon biomarkers in boilermakers exposed to metal fume and residual oil fly ash.

BACKGROUND: Boilermakers are occupationally exposed to known carcinogens. METHODS: The association of urinary 1-hydroxy-pyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure, with biomarkers of metal exposure (vanadium, chromium, manganese, nickel, copper, and lead) in boilermakers exposed to metal fume from welding and dust particulates from residual oil fly ash (ROFA) was examined. A repeated measures cohort study was conducted during the overhaul of an oil-fired boiler. Twice-daily urine samples were obtained for 5 days and analyzed for cotinine, 1-OHP, and metals. Generalized estimating equations (GEE) were used to model the multivariate relationship of 1-OHP to the explanatory variables. RESULTS: Metal and 1-OHP levels were determined for 165 urine samples from 20 boilermakers and these levels increased during the workweek. However, the 1-OHP level was not significantly associated with any individual metal level at any time point. CONCLUSION: This suggests that boilermakers were occupationally exposed to PAH and metals, but 1-OHP as a PAH biomarker was unable to serve as a surrogate marker of metal exposure for the metals measured in this study.

Adolescent↗

PubMed2005

Interaction between environmental tobacco smoke and arsenic methylation ability on the risk of bladder cancer.

OBJECTIVE: Arsenic exposure and environmental tobacco smoke (ETS) have been suspected to be associated with bladder cancer risk. We hypothesize that interaction between ETS and the ability to methylate arsenic, a detoxification pathway, modifies the risk of bladder cancer. METHODS: From January 1996 to December 1999, we identified 41 newly diagnosed bladder cancer patients and 202 fracture and cataract patients at the National Cheng-Kung University (NCKU) Medical Center. The levels of urinary arsenic species [As(III), As(V), MMA(V), and DMA(V)] were determined in all subjects. RESULTS: We found significant interaction between ETS and secondary methylation index (SMI) on the risk of bladder cancer (p=0.02). Among non-smokers with a high primary methylation index (PMI), the risk of bladder cancer was lower in subjects exposed to ETS (OR, 0.37; 95% CI, 0.14-0.96) than in subjects without exposure to ETS. Among non-smokers without ETS, the risk of bladder cancer was 4.7 times higher in subjects with a low SMI (95% CI, 1.30-16.81) than in subjects with a high SMI. CONCLUSIONS: Ability to methylate arsenic plays an important role in reducing the risk of bladder cancer attributable to the continuation of arsenic exposure from drinking water and from ETS exposure.

Aged↗

PubMed2005

Obesity and cardiovascular disease risk factors in firefighters: a prospective cohort study.

OBJECTIVE: Obesity, despite being a significant determinant of fitness for duty, is reaching epidemic levels in the workplace. Firefighters' fitness is important to their health and to public safety. RESEARCH METHODS AND PROCEDURES: We examined the distribution of BMI and its association with major cardiovascular disease (CVD) risk factors in Massachusetts firefighters who underwent baseline (1996) and annual medical examinations through a statewide medical surveillance program over 5 years of follow-up. We also evaluated firefighters' weight change over time. RESULTS: The mean BMI among 332 firefighters increased from 29 at baseline to 30 at the follow-up examination (2001), and the prevalence of obesity increased from 35% to 40%, respectively (p < 0.0001). In addition, the proportion of firefighters with extreme obesity increased 4-fold at follow-up (from 0.6% to 2.4%, p < 0.0001). Obese firefighters were more likely to have hypertension (p = 0.03) and low high-density lipoprotein-cholesterol (p = 0.01) at follow-up. Firefighters with extreme obesity had an average of 2.1 CVD risk factors (excluding obesity) in contrast to 1.5 CVD risk factors for normal-weight firefighters (p = 0.02). Finally, on average, normal-weight firefighters gained 1.1 pounds, whereas firefighters with BMI > or = 35 gained 1.9 pounds per year of active duty over 5 years of follow-up. DISCUSSION: Obesity is a major concern among firefighters and shows worsening trends over time. Periodic medical evaluations coupled with exercise and dietary guidelines are needed to address this problem, which threatens firefighters' health and may jeopardize public safety.

Adult↗

PubMed2005

Molecular epidemiology of non-small cell lung cancer.

Although smoking is the primary risk factor for most lung cancers, genetic predisposition may play an important role. Familial aggregation studies suggest a greater genetic component in the risk for younger individuals developing lung cancer, for lifetime nonsmokers, and possibly for women. Low-penetrance, high-prevalence polymorphic genes may explain part of this genetic predisposition. Functional polymorphisms of xenobiotic metabolism may alter the total exposure of tobacco carcinogens in the host. Subtle alterations in the DNA repair, inflammatory, and cell cycle pathways may also alter lung cancer susceptibility. The role of individual polymorphisms has been evaluated for several genes including the CYP and glutathione s-transferase superfamilies, and the NAT genes; DNA repair genes such as XPD (nucleotide excision pathway), XRCC1 (base excision pathway), and MGMT; and tumor suppressor or cell cycle genes such as p53. Molecular epidemiological studies are now focused on building larger databases from existing smaller studies and developing strategies to simultaneously evaluate multiple polymorphisms and genes within the same pathway.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Exposure to fuel-oil ash and welding emissions during the overhaul of an oil-fired boiler.

The health effects of exposure to vanadium in fuel-oil ash are not well described at levels ranging from 10 to 500 microg/m(3). As part of a larger occupational epidemiologic study that assessed these effects during the overhaul of a large oil-fired boiler, this study was designed to quantify boilermakers' exposures to fuel-oil ash particles, metals, and welding gases, and to identify determinants of these exposures. Personal exposure measurements were conducted on 18 boilermakers and 11 utility workers (referents) before and during a 3-week overhaul. Ash particles < 10 microm in diameter (PM(10), mg/m(3)) were sampled over full work shifts using a one-stage personal size selective sampler containing a polytetrafluoroethylene filter. Filters were digested using the Parr bomb method and analyzed for the metals vanadium (V), nickel (Ni), iron (Fe), chromium (Cr), cadmium (Cd), lead (Pb), manganese (Mn), and arsenic (As) by inductively coupled plasma mass spectrometry. Nitrogen dioxide (NO(2)) was measured with an Ogawa passive badge-type sampler and ozone (O(3)) with a personal active pump sampler.Time-weighted average (TWA) exposures were significantly higher (p < 0.05) for boilermakers than for utility workers for PM(10) (geometric mean: 0.47 vs. 0.13 mg/m(3)), V (8.9 vs. 1.4 microg/m(3)), Ni (7.4 vs. 1.8 microg/m(3)) and Fe (56.2 vs. 11.2 microg/m(3)). Exposures were affected by overhaul time periods, tasks, and work locations. No significant increases were found for O(3) or NO(2) for boilermakers or utility workers regardless of overhaul period or task group. Fuel-oil ash was a major contributor to boilermakers' exposure to PM(10) and metals. Vanadium concentrations sometimes exceeded the 2003 American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value.

Adult↗

PubMed2005

Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion.

OBJECTIVE: Clinical predictors for acute respiratory distress syndrome (ARDS) have been studied in few prospective studies. Although transfusions are common in the intensive care unit, the role of submassive transfusion in non-trauma-related ARDS has not been studied. We describe here the clinical predictors of ARDS risk and mortality including the role of red cell transfusion. DESIGN: Observational prospective cohort. SETTING: Intensive care unit of Massachusetts General Hospital. PATIENTS: We studied 688 patients with sepsis, trauma, aspiration, and hypertransfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty-one (32%) subjects developed ARDS with a 60-day mortality rate of 46%. Significant predictors for ARDS on multivariate analyses included trauma (adjusted odds ratio [ORadj] 0.22, 95% confidence interval [CI] 0.09-0.53), diabetes (ORadj 0.58, 95% CI 0.36-0.92), direct pulmonary injury (ORadj 3.78, 95% CI 2.45-5.81), hematologic failure (ORadj 1.84, 95% CI 1.05-3.21), transfer from another hospital (ORadj 2.08, 95% CI 1.33-3.25), respiratory rate >33 breaths/min (ORadj 2.39, 95% CI 1.51-3.78), hematocrit >37.5% (ORadj 1.77, 95% CI 1.14-2.77), arterial pH <7.33 (ORadj 2.00, 95% CI 1.31-3.05), and albumin </=2.3 g/dL (ORadj 1.80, 95% CI 1.18-2.73). Packed red blood cell transfusion was associated with ARDS (ORadj 1.52, 95% CI 1.00-2.31, p = .05). Significant predictors for mortality in ARDS included age (ORadj 1.96, 95% CI 1.50-2.53), Acute Physiology and Chronic Health Evaluation III score (ORadj 1.78, 95% CI 1.16-2.73), trauma (ORadj 0.075, 95% CI 0.006-0.96), corticosteroids before ARDS (ORadj 4.65, 95% CI 1.47-14.7), and arterial pH <7.22 (ORadj 2.32, 95% CI 1.02-5.25). Packed red blood cell transfusions were associated with increased mortality in ARDS (ORadj 1.10 per unit transfused; 95% CI 1.04-1.17) with a significant dose-dependent response (p = .02). CONCLUSIONS: Important predictors for the development of and mortality in ARDS were identified. Packed red blood cell transfusion was associated with an increased development of and increased mortality in ARDS.

Adolescent↗

PubMed2005

Dietary iron, zinc, and calcium and the risk of lung cancer.

BACKGROUND: Iron, zinc, and calcium are all involved in the metabolism of reactive oxygen species and may compete with each other for similar binding sites. Dietary intakes of these micronutrients have been associated with altered risks of colorectal, breast, and prostate cancers. METHODS: In this Massachusetts hospital-based case-control study of 923 patients with lung cancer and 1125 healthy controls, we studied the associations between dietary iron, zinc, and calcium intake and the risk of lung cancer. Dietary intake was assessed at the time of recruitment (1992 to 2000) with the use of a 126-item semiquantitative food-frequency questionnaire. We analyzed the data using multiple logistic regression models adjusting for smoking history and other potential risk factors. RESULTS: The adjusted odds ratios of dietary iron, zinc, and calcium from food sources were 1.45 (95% confidence interval=1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29), respectively, for the highest quintile versus the lowest quintile of each micronutrient. Stronger associations between micronutrients and lung cancer risk were found when iron, zinc, and calcium were included together in the same model. The associations between dietary micronutrients intake and lung cancer risk were stronger among current smokers than among former smokers. When we examined intake from supplements as well as diet, associations were similar to those for diet alone. CONCLUSIONS: Dietary iron, zinc, and calcium may play an important role in the development of lung cancer, especially among current smokers. These results need to be confirmed in large prospective studies.

Adult↗

PubMed2005

Estimation of personal exposures to particulate matter and metals in boiler overhaul work.

OBJECTIVE: We sought to develop an algorithm and estimate unmeasured exposures to particulate matter (PM) and metals in an epidemiologic study of boilermakers. METHODS: The algorithm was based on limited measurements and workers' task and time activity patterns. Half of the measurements were used to develop exposure estimates for unmeasured person days. The other half was used for method validation. RESULTS: The validation demonstrated good approximations of actual exposures with differences less than 5% for PM and vanadium (V). Average estimated exposures to PM (mg/m3) and V (microg/m3) were significantly higher for workers doing boiler repair than utility work (0.36 vs. 0.09 for PM and 5.99 vs. 0.38 for V). CONCLUSIONS: This algorithm provided reasonably accurate exposure indices for our epidemiologic study in this population. It also is likely applicable to similar exposure scenarios in other studies.

Air Pollutants, Occupational↗

PubMed2005

Biomarker research in occupational health.

OBJECTIVES: A variety of biomarkers have been used to study worker populations, and these studies have achieved different levels of success in the improvement of occupational health. METHODS: Successful application of biomarker research is dependent upon several important factors: ability to identify hazardous substances from the exposure to a variety of substances, relevance to the development of disease, and usefulness for health risk assessment. RESULTS: Besides the traditional biomarkers for exposure, biological effects, and health risk, new biomarkers for susceptibility and genome-wide responses are being used to improve our understanding of occupational health at a higher and, perhaps, more precise level. CONCLUSIONS: In addition, there is a continued need to develop and apply biomarkers that can be used to provide real-time detection of excessive exposure to hazardous substances in the workplace, especially from unexpected fugitive emissions. These topics are discussed in the review.

Benzene↗

PubMed2005

Physicians' initial management of acute low back pain versus evidence-based guidelines. Influence of sciatica.

BACKGROUND: Little information is available on physician characteristics and patient presentations that may influence compliance with evidence-based guidelines for acute low back pain. OBJECTIVE: To assess whether physicians' management decisions are consistent with the Agency for Health Research Quality's guideline and whether responses varied with the presentation of sciatica or by physician characteristics. DESIGN: Cross-sectional study using a mailed survey. PARTICIPANTS: Participants were randomly selected from internal medicine, family practice, general practice, emergency medicine, and occupational medicine specialties. MEASUREMENTS: A questionnaire asked for recommendations for 2 case scenarios, representing patients without and with sciatica, respectively. RESULTS: Seven hundred and twenty surveys were completed (response rate=25%). In cases 1 (without sciatica) and 2 (with sciatica), 26.9% and 4.3% of physicians fully complied with the guideline, respectively. For each year in practice, the odds of guideline noncompliance increased 1.03 times (95% confidence interval [CI]=1.01 to 1.05) for case 1. With occupational medicine as the referent specialty, general practice had the greatest odds of noncompliance (3.60, 95% CI=1.75 to 7.40) in case 1, followed by internal medicine and emergency medicine. Results for case 2 reflected the influence of sciatica with internal medicine having substantially higher odds (vs case 1) and the greatest odds of noncompliance of any specialty (6.93, 95% CI=1.47 to 32.78), followed by family practice and emergency medicine. CONCLUSIONS: A majority of primary care physicians continue to be noncompliant with evidence-based back pain guidelines. Sciatica dramatically influenced clinical decision-making, increasing the extent of noncompliance, particularly for internal medicine and family practice. Physicians' misunderstanding of sciatica's natural history and belief that more intensive initial management is indicated may be factors underlying the observed influence of sciatica.

Acute Disease↗

PubMed2005

Modeling lung cancer risk in case-control studies using a new dose metric of smoking.

Many approaches have been taken to adjust for smoking in modeling cancer risk. In case-control studies, these metrics are often used arbitrarily rather than being based on the properties of the metric in the context of the study. Depending on the underlying study design, hypotheses, and base population, different metrics may be deemed most appropriate. We present our approach to evaluating different smoking metrics. We examine the properties of a new metric, "logcig-years", that we initially derived from using a biological model of DNA adduct formation. We compare this metric to three other smoking metrics, namely pack-years, square-root pack-years, and a model in which smoking duration and intensity are separate variables. Our comparisons use generalized additive models and logistic regression to examine the relationship between the logit probability of cancer and each of the metrics, adjusting for other covariates. All models were fit using data from a lung cancer study of 1,275 cases and 1,269 controls that has focused on gene-smoking relationships. There was a very significant, linear relationship between logcig-years and the logit probability of lung cancer in this sample, without any need to adjust for smoking status. These properties together were not shared by the other metrics. In this sample, logcig-years captured more information about smoking that is important in lung cancer risk than the other metrics. In conclusion, we provide a general framework for evaluating different smoking metrics in studies where smoking is a critical variable.

Adult↗

PubMed2005

A urinary metabolite of phenanthrene as a biomarker of polycyclic aromatic hydrocarbon metabolic activation in workers exposed to residual oil fly ash.

Residual oil fly ash is a chemically complex combustion product containing a significant component of potentially carcinogenic transition metals and polycyclic aromatic hydrocarbons (PAH). Various biomarkers of PAH exposure have been investigated previously, most notably 1-hydroxypyrene (1-OHP), in urine. In this study, we assessed the utility of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT), a metabolite of phenanthrene, to detect occupational PAH exposure. Urine samples collected across the workweek were analyzed for 1-OHP and trans, anti-PheT in boilermakers (n = 20) exposed to residual oil fly ash. Median baseline urinary trans, anti-PheT concentrations were 0.50 microg/g creatinine in current tobacco smokers and 0.39 microg/g creatinine in nonsmokers. Median baseline urinary 1-OHP concentrations in smokers and nonsmokers were 0.31 and 0.13 microg/g creatinine, respectively. To study further the effect of smoking exposure on the urinary PAH markers, urinary cotinine was used. Although urinary trans, anti-PheT and 1-OHP concentrations were correlated (Spearman r = 0.63; P < 0.001) for all subjects, the regression coefficient between log-transformed trans, anti-PheT and log 1-OHP was statistically significant only for subjects with low levels of urinary cotinine or for nonsmokers. Each 1-unit increase in log 1-OHP was associated with a 0.77-unit increase (95% confidence interval, 0.45-1.09) in log trans, anti-PheT in subjects with low levels of urinary cotinine (P < 0.001). In these subjects, dichotomized occupational exposure status was a significant predictor of log trans, anti-PheT (P = 0.02) but not of log 1-OHP (P = 0.2). In conclusion, we found that urinary trans, anti-PheT was detected in levels comparable with 1-OHP in occupationally exposed workers, particularly nonsmokers. This study shows that urinary trans, anti-PheT may be an effective biomarker of uptake and metabolic activation of PAHs.

Adult↗

PubMed2005

Matrix metalloproteinase-1 promoter polymorphism and lung cancer risk.

Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2G allele of the MMP-1 -1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% CI, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% CI, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males.

Adult↗