| 1. |
- Bonassi, Stefano, et al.
(author)
-
Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries
- 2008
-
In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 29:6, s. 1178-1183
-
Journal article (peer-reviewed)abstract
- Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37-3.70), RRhigh = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.
|
|
| 2. |
- Gallo, Valentina, et al.
(author)
-
Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
-
In: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
-
Journal article (peer-reviewed)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
|
|
| 3. |
|
|
| 4. |
- Peters, Susan, et al.
(author)
-
Polycyclic aromatic hydrocarbon exposure, urinary mutagenicity, and DNA adducts in rubber manufacturing workers
- 2008
-
In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 17:6, s. 1452-1459
-
Journal article (peer-reviewed)abstract
- Objectives: Several studies have suggested that genotoxic risks might still be present in the contemporary rubber manufacturing industry. Previously, we observed elevated levels of urinary mutagenicity and bladder DNA adducts in rubber workers. Presently, we investigated whether DNA adducts in peripheral blood mononuclear cells (PBMC) and/or urothelial cells may be caused by polycyclic aromatic hydrocarbons or other genotoxic compounds. Methods: Spot urine samples from 116 rubber manufacturing workers were collected on Sunday and during the workweek (post-shift) to determine 1-hydroxypyrene and mutagenicity levels. For 52 nonsmokers, urothelial cell DNA adducts and PBMC DNA adducts were measured additionally. Results: Urinary 1-hydroxypyrene levels were significantly higher in workweek samples compared with Sunday (P = 0.0001). This increase was not uniform across tasks and only reached statistical significance for the curing department (+99%; P = 0.003). Weekday urinary mutagenicity was significantly increased for mixing (+56%) and curing (+21%) workers when compared with that for Sunday. Total urothelial cell DNA adducts were related to urinary 1-hydroxypyrene (P = 0.021) and mutagenicity (P = 0.027). No significant relationship was found between the adduct levels in PBMC and urothelial cells or between the former and urinary 1-hydroxypyrene or mutagenicity. Conclusions: Workers in the compounding, mixing, and curing departments were at highest genotoxic risk among rubber manufacturing workers. Increased levels of urinary 1-hydroxypyrene, mutagenicity, and urothelial cell DNA adducts were found in these workers. Urothelial cell and PBMC DNA adducts were not related, hinting possibly to the presence of specific bladder carcinogens in the rubber manufacturing industry.
|
|
| 5. |
- Purdue, Mark P, et al.
(author)
-
Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers.
- 2007
-
In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 62:1, s. 51-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow-up were available, were analysed. METHODS: Cancer incidence for 1971-2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non-lung tobacco-related cancers, other cancers, total mortality) were also investigated. RESULTS: 834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow-up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality. CONCLUSIONS: Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk.
|
|
| 6. |
- van Es, Michael A, et al.
(author)
-
Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
-
Journal article (peer-reviewed)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
|
|
