Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ...ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age‐adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8–143.2) for SqCC, 111.3 (95% CI: 69.8–177.5) for SCLC and 21.9 (95% CI: 16.6–29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5–124.6), 108.6 (95% CI: 50.7–232.8) and 16.8 (95% CI: 9.2–30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.
An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between ...lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.
Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.
The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)).
SES remained a risk factor for lung cancer after adjustment for smoking behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of ...the environmental threats to health.
We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe.
In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5-11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011-2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with health-based guidelines.
Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values.
We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck
cancers is not clear because studies have used various methods to quantify ...the excess head and neck cancer burden.
Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168
controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative
interaction parameter ( ψ ) and population attributable risks (PAR).
Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer
risk ( ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for
head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol
combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer),
by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe,
51% in North America, 83% in Latin America).
Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head
and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol
use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol
Biomarkers Prev 2009;18(2):541–50)
Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously.
...Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma.
The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case-control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking.
Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio OR, 1.33; 95% confidence interval CI, 1.20-1.48 and OR, 1.50; 95% CI, 1.21-1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33-4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis "only." Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter.
Findings from this large international case-control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer.
Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the ...International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
Background: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water. Objectives: We aimed to quantify skin ...cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism. Methods: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case-control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. Results: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. Conclusion: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L.
Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack ...adequate control for potential confounders and only a few studies have reported on exposure-response relationships.
Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders.
The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure.
Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant.
Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.
We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated ...the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 × 10−10 and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and ...methylation reactions, catalyzed by reductases and methyltransferases. Objectives: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. Methods: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylenetetrahydrofolate reductase (MTHFR). Results: The results show that the M287T (T→C) polymorphism in the AS3MT gene, the A222V (C→T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 µg/L arsenic in urine. Females < 60 years of age had, in general, higher methylation efficiency than males, indicating an influence of sex steroids. That might also explain the observed better methylation in overweight or obese women, compared with normal weight men. The influence of the M287T (T→C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. Conclusions: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic.
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