Ultra-sensitive troponin I is an independent predictor of incident coronary heart disease in the general population

Abstract

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.2 years, 51.5% women) comprising 803 CHD cases and 1942 non-cases. Ultrasensitive troponin I was detectable in 99.9% of available case-cohort samples. In an age- and sex-adjusted model, individuals in the highest quartile of the troponin distribution had a more than threefold increased risk for CHD events compared to those in the bottom quartile [hazard ratio, HR, 3.11; 95% confidence interval (CI) 2.15–4.49]. In a model adjusting for cardiovascular risk factors including C-reactive protein, cystatin C and N-terminal pro brain natriuretic peptide, individuals in the highest troponin I quartile still showed a hazard ratio of 2.58 (95% CI 1.66–4.00) for incident CHD as compared to those in the lowest quartile. Ultrasensitive troponin I was detectable in almost all individuals of a study sample reflecting middle-aged to elderly European general population. Ultrasensitive troponin concentrations exhibit an independent, graded, positive relation with incident CHD.

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Occupational formaldehyde and amyotrophic lateral sclerosis

Abstract

Prior studies have yielded inconsistent evidence regarding the association between formaldehyde exposure and amyotrophic lateral sclerosis (ALS). We conducted a population case–control study in the Danish National Registries on the relationship between occupationally-derived formaldehyde exposure and ALS. Occupational history was obtained from a comprehensive and prospectively recorded pension database of all paid work in Denmark since 1964, and was linked to a job-exposure matrix to derive individual exposure estimates. Each case was matched to 4 age- and sex-matched population controls alive on the date of the case diagnosis via risk set sampling, and odds ratios and confidence intervals (CI) were calculated via conditional logistic regression, adjusting for potential confounders. There were 3650 incident cases of ALS in the Danish National Patient Register from 1982 to 2009. Among controls, 25% were ever employed in jobs with a positive prevalence of formaldehyde exposure. Exposure to formaldehyde was associated with a 1.3-fold increased rate of ALS (95% CI 1.2–1.4). This study suggests that formaldehyde exposure, or employment in formaldehyde-exposed occupations, is related to the risk of ALS.

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Occupational exposure to diesel motor exhaust and risk of lung cancer by histological subtype: a population-based case–control study in Swedish men

Abstract

We investigated occupational exposure to diesel motor exhaust (DME) and the risk of lung cancer by histological subtype among men, using elemental carbon (EC) as a marker of DME exposure. 993 cases and 2359 controls frequency-matched on age and year of study inclusion were analyzed by unconditional logistic regression in this Swedish case–control study. Work and smoking histories were collected by a questionnaire and telephone interviews. DME was assessed by a job-exposure matrix. We adjusted for age, year of study inclusion, smoking, occupational exposure to asbestos and combustion products (other than motor exhaust), residential exposure to radon and exposure to air pollution from road traffic. The OR for lung cancer for ever vs. never exposure to DME was 1.15 (95% CI 0.94–1.41). The risk was higher for squamous and large cell, anaplastic or mixed cell carcinoma than for alveolar cell cancer, adenocarcinoma and small cell carcinoma. The OR in the highest quartile of exposure duration (≥34 years) vs. never exposed was 1.66 (95% CI 1.08–2.56; p for trend over all quartiles: 0.027) for lung cancer overall, 1.73 (95% CI 1.00–3.00; p: 0.040) for squamous cell carcinoma and 2.89 (95% CI 1.37–6.11; p: 0.005) for the group of undifferentiated, large cell, anaplastic and mixed cell carcinomas. We found no convincing association between exposure intensity and lung cancer risk. Long-term DME exposure was associated with an increased risk of lung cancer, particularly to squamous cell carcinoma and the group of undifferentiated, large cell, anaplastic or mixed carcinomas.

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Long-term a posteriori dietary patterns and risk of hip fractures in a cohort of women

Abstract

Dietary pattern analysis is a useful tool to study the importance of food components in the context of a diet and how they relate to health and disease. The association between dietary patterns and fractures is at present uncertain. We aimed to study associations between dietary patterns and risk of hip fracture in the Swedish Mammography Cohort, including 56,736 women (median baseline age 52 years). Diet data was collected in food frequency questionnaires at two investigations and dietary patterns were defined by principal component analysis using 31 food groups. Information on hip fractures was collected from the Swedish National Patient Register. Multivariable adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated in Cox proportional hazards regression analysis. The two patterns identified—the healthy and Western/convenience dietary patterns—were time-updated and analysed. During a median follow-up time of 25.5 years, 4997 women experienced a hip fracture. Hip fracture rate was 31% lower in the highest compared to the lowest quartile of the healthy dietary pattern [HR (95% CI) 0.69 (0.64; 0.75)]. In contrast, women in the highest compared to the lowest quartile of the Western/convenience dietary pattern had a 50% higher [HR (95% CI) 1.50 (1.38; 1.62)] hip fracture rate. Further, in each stratum of a Western/convenience dietary pattern a higher adherence to a healthy dietary pattern was associated with less hip fractures. The present results suggest that a varied healthy diet may be beneficial for the prevention of fragility fractures in women.

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UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

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UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

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UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

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