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"Very hot beverage" (>65°C) consumption is an IARC probable carcinogen and may contribute to the African esophageal cancer burden. We conducted community cross-sectional exposure studies of hot beverage consumption in Kenya and Malawi during 2018-2019, aiming to: (i) implement a detailed measurement protocol incorporating three measurements of sip temperature and volume so as to predict each sip's intra-esophageal liquid temperature (IELT); (ii) examine variations by seasonality, drinking venue and age, including children. 246 participants were included, of whom 236 had drink measurements (52 children and 183 adults). Among adults, mean (SD) temperatures at first sip were 67 (9) and 68 (7) °C in Kenya and Malawi respectively, i.e. 58 and almost 70 % of first sips were > 65 °C. In both countries, adults exhibited a protective habit of smaller sips at higher temperatures (mean 11 mL at first sip), whereas the larger middle sip (20 mL) had the highest IELT (45 °C). The highest temperatures were observed in men and for drinks taken in social settings, whereas we did not detect seasonality or associations with other esophageal cancer risk factors. Measurements were difficult to make for 20 % (8/43) of Kenyan children whose drink was cooled by pouring between cups ('poesha'). Where poesha was not practiced, IELTs were lower in children (especially < 10 years) than in adults, owing to a mean of 8 °C cooler first sip temperature, however 20 % of first sips were > 65 °C. If very hot beverage consumption is an esophageal carcinogen, lowering sip temperatures and volumes in East Africa would form important prevention avenues., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The largest case-control study (Interphone study) investigating glioma risk related to mobile phone use showed a J-shaped relationship with reduced relative risks for moderate use and a 40% increased relative risk among the 10% heaviest regular mobile phone users, using a categorical risk model based on deciles of lifetime duration of use among ever regular users., Methods: We conducted Monte Carlo simulations examining whether the reported estimates are compatible with an assumption of no effect of mobile phone use on glioma risk when the various forms of biases present in the Interphone study are accounted for. Four scenarios of sources of error in self-reported mobile phone use were considered, along with selection bias. Input parameters used for simulations were those obtained from Interphone validation studies on reporting accuracy and from using a nonresponse questionnaire., Results: We found that the scenario simultaneously modeling systematic and random reporting errors produced a J-shaped relationship perfectly compatible with the observed relationship from the main Interphone study with a simulated spurious increased relative risk among heaviest users (odds ratio = 1.91) compared with never regular users. The main determinant for producing this J shape was higher reporting error variance in cases compared with controls, as observed in the validation studies. Selection bias contributed to the reduced risks as well., Conclusions: Some uncertainty remains, but the evidence from the present simulation study shifts the overall assessment to making it less likely that heavy mobile phone use is causally related to an increased glioma risk., Competing Interests: Disclosure: M.F. was vice chairman (2012–2020) of the International Commission on Non-Ionizing Radiation Protection, an independent body setting guidelines for nonionizing radiation protection. She has served as advisor to a number of national and international public advisory and research steering groups concerning the potential health effects of exposure to nonionizing radiation, currently for the World Health Organization. M.F. is the principal investigator of the Swedish part of the COSMOS study, which has been funded by the Swedish Research Council, AFA Insurance, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Radiation Safety Authority, and VINNOVA. VINNOVA received funds for this purpose from TeliaSonera AB, Ericsson AB, and Telenor Sverige AB, to cover part of the data collection (ended 2012). The provision of funds to the COSMOS study investigators via VINNOVA was governed by agreements that guarantee COSMOS’ complete scientific independence. The remaining authors declare they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention., Methods: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, during pregnancy and/or during post-natal period. Random effects meta-analysis was used to estimate summary effect sizes (ES) and 95% confidence intervals (CIs). We also quantified heterogeneity (I 2 ) across studies., Findings: A total of 4040 studies were identified, of which 181 studies (85 case-control and 96 cohort studies) met our criteria for inclusion. Of all eligible studies, 50% (n = 91) were conducted in Europe, 32% (n = 57) in North America, 9% (n = 16) in Australia, 8% (n = 15) in Asia, 1% (n = 2) in South America, and none in Africa. We found associations for some modifiable risk factors including childhood domestic exposures to insecticides (ES 1.44, 95% CI 1.20-1.73) and herbicides (ES 2.38, 95% CI 1.31-4.33). Maternal domestic exposure to insecticides (ES 1.45, 95% CI 1.09-1.94), maternal consumption of cured meat (ES 1.51, 95% CI 1.05-2.17) and coffee ≥ 2 cups/day (ES 1.45, 95% 95% CI 1.07-1.95) during pregnancy, and maternal exposure to benzene (ES 2.22; 95% CI 1.01-4.88) before conception were associated with CBTs in case-control studies. Also, paternal occupational exposure to pesticides (ES 1.48, 95% CI 1.23-1.77) and benzene (ES 1.74, 95% CI 1.10-2.76) before conception and during pregnancy were associated in case-control studies and in combined analysis. On the other hand, assisted reproductive technology (ART) (ES 1.32, 95% CI 1.05-1.67), caesarean section (CS) (ES 1.12, 95% CI 1.01-1.25), paternal occupational exposure to paint before conception (ES 1.56, 95% CI 1.02-2.40) and maternal smoking > 10 cigarettes per day during pregnancy (ES 1.18, 95% CI 1.00-1.40) were associated with CBT in cohort studies. Maternal intake of vitamins and folic acid during pregnancy was inversely associated in cohort studies. Hormonal/infertility treatment, breastfeeding, child day-care attendance, maternal exposure to electric heated waterbed, tea and alcohol consumption during pregnancy were among those not associated with CBT in both case-control and cohort studies., Conclusion: Our results should be interpreted with caution, especially as most associations between risk factors and CBT were discordant between cohort and case-control studies. At present, it is premature for any CBT to define specific primary prevention guidelines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents., Objectives: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking., Methods: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI)., Results: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8)., Discussion: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies., (© 2023 International Agency for Research on Cancer. International Agency for Research on Cancer retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease., Methods: Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case-control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS)., Results: We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case-control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease., Conclusions: Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention., (© 2023. The Author(s).)

Background: Gold mining activities in South Africa resulted in contamination of residential environment with uranium-rich wastes from mine tailings. Health of the people living around the mine tailings could be affected by uranium exposure due to its hazardous chemotoxic and radiological properties., Methods: We conducted a cross-sectional study to assess i) uranium (U) concentrations in individual hair samples of children and adults living in close proximity to mine tailings in Northeast- Soweto in Johannesburg, South Africa, and ii) the association between U concentrations in hair and various factors, including zone of residence, socio-demographic and housing characteristics. Sampling sites were divided into three zones based on the distance between a dwelling and a cluster of mine tailings (zone 1: <= 500 m, zone 2: 2-3 km away, zone 3: 4-5 km away). U concentrations in hair samples were measured using inductively coupled plasma mass spectrometry. To test the association between U concentrations and selected factors we used robust regression models with log-transformed U concentrations., Results: Among 128 subjects with available U measurements, 63 (49%) were children (ages 7-15 years) of which 38 were girls, the remaining 65 (51%) were adult females. Mean (median) U concentration in hair samples was 143 (92) µg/kg. In the mutually adjusted analyses, only an inverse association between age and U concentration in hair remained statistically significant, with geometric mean in children being 2.1 times higher compared to adults (P < 0.001). There was no evidence of an association between zones and U concentration (P = 0.42)., Conclusions: There was little evidence of association between U concentration in hair and distance from the mine tailings within the 5 km range, but overall concentrations were elevated compared to general population samples in other parts of the world. Children had statistically significantly higher geometric mean of uranium concentration in hair compared to adults. The results are important for improvement of mining waste policies and implementation of health monitoring and protective measures in populations at risk., Article Category: Research Article., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Background: Globally, lung cancer is the most frequent occupational cancer, but the risk associated with the occupations or occupational environment in Iran is not clear. We aimed to assess occupations with the risk of lung cancer., Methods: We used the IROPICAN nationwide case-control study data including 658 incident lung cancer cases and 3477 controls. We assessed the risk of lung cancer in relation to ever working in major groups of International Standard Classification of Occupations, high-risk occupations for lung cancer and duration of employment and lung cancer subtype among construction workers and farmers while controlling for cigarette smoking and opium consumption. We used unconditional regression logistic models to estimate ORs for the association between increased lung cancer risk and occupations., Results: We observed elevated ORs for lung cancer in male construction workers (OR=1.4; 95% CI: 1.0 to 1.8), petroleum industry workers (OR=3.2; 95% CI: 1.1 to 9.8), female farmers (OR=2.6; 95% CI: 1.3 to 5.3) and female bakers (OR=5.5; 95% CI: 1.0 to 29.8). A positive trend by the duration of employment was observed for male construction workers (p< 0.001). Increased risk of squamous cell carcinoma was observed in male construction workers (OR=1.9; 95% CI: 1.2 to 3.0) and female farmers (OR=4.3; 95% CI: 1.1 to 17.2), who also experienced an increased risk of adenocarcinoma (OR=3.8; 95% CI: 1.4 to 9.9)., Discussion: Although we observed associations between some occupations and lung cancer consistent with the literature, further studies with larger samples focusing on exposures are needed to better understand the occupational lung cancer burden in Iran., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case-control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons., Competing Interests: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.

Background: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project., Methods: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI)., Results: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP μg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk., Conclusions: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens., Impact: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Although several cross-sectional studies have shown that aircraft noise exposure was associated with an increased risk of hypertension, a limited number of longitudinal studies have addressed this issue. This study is part of the DEBATS (Discussion on the health effect of aircraft noise) research programme and aimed to investigate the association between aircraft noise exposure and the incidence of hypertension., Methods: In 2013, 1244 adults living near three major French airports were included in this longitudinal study. Systolic and diastolic blood pressure, as well as demographic and lifestyle factors, were collected at baseline and after 2 and 4 years of follow-up during face-to-face interviews. Exposure to aircraft noise was estimated for each participant's home address using noise maps. Statistical analyses were performed using mixed Poisson and linear regression models adjusted for potential confounding factors., Results: A 10 dB(A) increase in aircraft noise levels in terms of L den was associated with a higher incidence of hypertension (incidence rate ratio (IRR)=1.36, 95% CI 1.02 to 1.82). The association was also significant for L day (IRR 1.41, 95% CI 1.07; to 1.85) and L night (IRR 1.31, 95% CI 1.01 to 1.71). Systolic and diastolic blood pressure increased with all noise indicators., Conclusion: These results strengthen those obtained from the cross-sectional analysis of the data collected at the time of inclusion in DEBATS, as well as those from previous studies conducted in other countries. Hence, they support the hypothesis that aircraft noise exposure may be considered as a risk factor for hypertension., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development., Methods: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression., Results: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype., Conclusions: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted., (© 2021. The Author(s).)

Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterize the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression, and more specifically of TET2 demethylase that may be involved in the DNA hypermethylation following short-term E2 deprivation. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER connection mainly with two partner TF families, AP-1 and FOX. These interactions take place in the proximity of E2 deprivation-mediated differentially methylated and histone acetylated enhancers. Finally, while most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation, DNA hypermethylation and H3K27 deacetylation at certain enhancers were partially retained. Overall, these results show that inactivation of ER mediates rapid and mostly reversible epigenetic changes at enhancers, and bring new insight into early events, which may ultimately lead to endocrine resistance., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background : DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers' blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods : Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population ( n = 244), in relation to the child's dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results : Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions : This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.

Introduction: Lebanon is among the top countries worldwide in combined incidence and mortality of breast cancer, which raises concern about risk factors peculiar to this country. The underlying molecular mechanisms of breast cancer require elucidation, particularly epigenetics, which is recognized as a molecular sensor to environmental exposures., Purpose: We aim to explore whether DNA methylation levels of AHRR (marker of cigarette smoking), SLC1A5 and TXLNA (markers of alcohol consumption), and LINE-1 (a genome-wide repetitive retrotransposon) can act as molecular mediators underlying putative associations between breast cancer risk and pertinent extrinsic (tobacco smoking and alcohol consumption) and intrinsic factors [age and body mass index (BMI)]., Methods: This is a cross-sectional pilot study which includes breast cancer cases (N = 65) and controls (N = 54). DNA methylation levels were measured using bisulfite pyrosequencing on available peripheral blood samples (N = 119), and Multivariate Imputation by Chained Equations (MICE) was used to impute missing DNA methylation values in remaining samples. Multiple mediation analysis was performed to assess direct and indirect (via DNA methylation) effects of intrinsic and extrinsic factors on breast cancer risk., Results: In relation to exposure, AHRR hypo-methylation was associated with cigarette but not waterpipe smoking, suggesting potentially different biomarkers of these two forms of tobacco use; SLC1A5 and TXLNA methylation were not associated with alcohol consumption; LINE-1 methylation was inversely associated with BMI (β-value [95% confidence interval (CI)] = -0.04 [-0.07, -0.02]), which remained significant after adjustment for age, smoking and alcohol consumption. In relation to breast cancer, there was no detectable association between AHRR, SLC1A5 or TXLNA methylation and cancer risk, but LINE-1 methylation was significantly higher in breast cancer cases when compared to controls (mean ± SD: 72.00 ± 0.66 versus 70.89 ± 0.73, P = 4.67 × 10 -14 ). This difference remained significant after adjustment for confounders (odds ratio (OR) [95% CI] = 9.75[3.74, 25.39]). Moreover, LINE-1 hypo-methylation mediated 83% of the inverse effect of BMI on breast cancer risk., Conclusion: This pilot study demonstrates that alterations in blood LINE-1 methylation mediate the inverse effect of BMI on breast cancer risk. This warrants large scale studies and stratification based on clinic-pathological types of breast cancer., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project., Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens., Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0)., Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey "vie après cancer" VICAN (January-June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue ( p = 0.03) and an increase in cognitive sequelae was reported ( p = 0.03). Two latent classes were identified-functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.

Objectives: A historical cohort study of cancer mortality is being conducted among workers in a chrysotile mine and its enrichment factories in the town of Asbest, Russian Federation. Because individual-level information on tobacco use is not available for Asbest Chrysotile Cohort members, a cross-sectional survey of smoking behaviours was conducted among active and retired workers., Methods: Self-administered questionnaires were completed by active workers during meetings organised by occupational safety personnel. Retired workers completed questionnaires during meetings of the Veterans Council or were interviewed via telephone or in person. Of the respondents, 46% could be linked to the Asbest Chrysotile Cohort. Among those, logistic regression models were used to assess associations between smoking and cumulative dust exposure., Results: Among men, smoking prevalence was high and relatively consistent across birth decades (average, 66%), and was similar in workers across all levels of cumulative dust exposure (p trend, 0.44). Among women, the prevalence increased from <10% in those born before 1960 to 30% in those born after 1980, and smoking was associated with exposure to dust versus not exposed to dust (p value, 0.006), but did not vary appreciably across workers in different cumulative dust exposure categories (p trend, 0.29)., Conclusions: Our study suggests that cross-sectional surveys may be a useful tool for understanding the potential health impact from smoking in occupational cohorts, including possible confounding by smoking. This survey showed that adjustment at the age group level among women is needed to reduce residual confounding and account for smoking patterns, which have changed substantially over time., Competing Interests: Competing interests: EVK and SVK reported receiving, on behalf of their institutes and personally through consulting firms, payments from companies to evaluate exposure to asbestos and risk of asbestos-related disease in those workplaces. All other authors have no competing interests to declare. For full transparency, EVK reported participation as an occupational and environmental health expert as part of the delegation of the Russian Ministry of Health at multiple World Health Assembly meetings as well as at the Conference of the Parties to the Basel and Rotterdam Conventions. EVK and SVK reported attending meetings organized by the International Chrysotile Association and reported that all expenses for attendance were paid by their respective institutes., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists., Methods: To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France ( n = 20) and hot porridge consumers ( n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature., Results: Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3-20.7] of hotter (+9.5°C; 95% CI, 6.2-12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent., Conclusions: Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols., Impact: This study provides a logistically feasible framework for assessing human exposure to hot beverages., (©2019 American Association for Cancer Research.)

Introduction: Responsibility analysis allows the evaluation of crash risk factors from crash data only, but requires a reliable responsibility assessment. The aim of the present study is to predict expert responsibility attribution (considered as a gold-standard) from explanatory variables available in crash data routinely recorded by the police, according to a data-driven process with explicit rules., Method: Driver responsibility was assessed by experts using all information contained in police reports for a sample of about 5000 injury crashes that occurred in France in 2011. Three statistical methods were used to predict expert responsibility attribution: logistic regression with L1 penalty, random forests, and boosting. Potential predictors of expert attribution referred to inappropriate driver actions and to external conditions at the time of the crash. Logistic regression was chosen to construct a score to assess responsibility for drivers and riders in crashes involving one or more motor vehicles, or involving a cyclist or pedestrian., Results: Cross-validation showed that our tool can predict expert responsibility assessments on new data sets. In addition, responsibility analyses performed using either the expert responsibility or our predicted responsibility return similar odds ratios. Our scoring process can then be used to reliably assess responsibility based on national police report databases, provided that they include the information needed to construct the score., (Copyright © 2019 Elsevier Ltd and National Safety Council. All rights reserved.)

Background: An estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1), based on sufficient evidence of lung cancer from epidemiological studies., Objective: To conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking., Methods: The literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers's test and Begg's test., Results: Forty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For 'ever' compared with 'never' being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I 2 =26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I 2 =44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I 2 =41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I 2 =6.3%; 15 studies) among 'shipyard welders', 1.44 (95% CI 1.07 to 1.95; I 2 =35.8%; 3 studies) for 'mild steel welders' and 1.38 (95% CI 0.89 to 2.13; I 2 =68.1%; 5 studies) among 'stainless steel welders'. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype., Conclusions: These results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide. We next show that the glycidamide mutational signature is found in a full one-third of approximately 1600 tumor genomes corresponding to 19 human tumor types from 14 organs. The highest enrichment of the glycidamide signature was observed in the cancers of the lung (88% of the interrogated tumors), liver (73%), kidney (>70%), bile duct (57%), cervix (50%), and, to a lesser extent, additional cancer types. Overall, our study reveals an unexpectedly extensive contribution of acrylamide-associated mutagenesis to human cancers., (© 2019 Zhivagui et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women., Methods: Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures., Results: The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways., Conclusions: These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Gliomas are the most common cancer of the brain, with a poor prognosis in particular for glioblastoma. In 2014, a study suggested reduced survival in relation to latency of mobile phone use among glioblastoma patients. A joint epidemiological/experimental project to study effects of RF-EMF on tumor development and progression was established. The current analysis relates to the epidemiological part and addresses whether pre-diagnostic mobile phone use was associated with survival among glioma patients., Methods: Glioma cases (n = 806) previously enrolled in a collaborative population-based case-control study in Denmark, Finland and Sweden were followed up for survival. Vital status, date of death, date of emigration, or date last known to be alive was obtained based on registry linkages with a unique personal ID in each country. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) stratified by country. Covariates investigated were sex, age, education, histology, treatment, anatomic location and marital status., Results: No indication of reduced survival among glioblastoma patients was observed for various measures of mobile phone use (ever regular use, time since start of regular use, cumulative call time overall or in the last 12 months) relative to no or non-regular use. All significant associations suggested better survival for mobile phone users. Results were similar for high-grade and low-grade gliomas., Conclusions: We found no evidence of reduced survival among glioma patients in relation to previous mobile phone use.

Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC's Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30-39 year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa., (Copyright © 2018. Published by Elsevier Ltd.)

Circulating miRNAs have shown great promises as noninvasive diagnostic and predictive biomarkers in several solid tumors. While the miRNA profiles of renal tumors have been extensively explored, knowledge of their circulating counterparts is limited. Our study aimed to provide a large-scale genome-wide profiling of plasma circulating miRNA in clear-cell renal cell carcinoma (ccRCC). Plasma samples from 94 ccRCC cases and 100 controls were screened for 754 circulating micro-RNAs (miRNA) by TaqMan arrays. Analyses including known risk factors for renal cancer-namely, age, sex, hypertension, obesity, diabetes, tobacco smoking and alcohol consumption-highlighted that circulating miRNA profiles were tightly correlated with the stage of the disease. Advanced tumors, characterized as stage III and IV, were associated with specific miRNA signatures that significantly differ from both controls and earlier stage ccRCC cases. Molecular pathway enrichment analyses of their gene targets showed high similarities with alterations observed in renal tumors. Plasma circulating levels of miR-150 were significantly associated with RCC-specific survival and could marginally improve the predictive accuracy of clinical parameters in our series, including age at diagnosis, sex and conventional staging. In summary, our results suggest that circulating miRNAs may provide insights into renal cell carcinoma progression., (© 2017 UICC.)

Background: Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited., Methods: We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours., Results: We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort., Conclusions: We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.

Aim of the Study: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification., Methods: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age., Results: We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls., Conclusion: Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

TP53 gene mutations are one of the most frequent somatic events in cancer. The IARC TP53 Database (http://p53.iarc.fr) is a popular resource that compiles occurrence and phenotype data on TP53 germline and somatic variations linked to human cancer. The deluge of data coming from cancer genomic studies generates new data on TP53 variations and attracts a growing number of database users for the interpretation of TP53 variants. Here, we present the current contents and functionalities of the IARC TP53 Database and perform a systematic analysis of TP53 somatic mutation data extracted from this database and from genomic data repositories. This analysis showed that IARC has more TP53 somatic mutation data than genomic repositories (29,000 vs. 4,000). However, the more complete screening achieved by genomic studies highlighted some overlooked facts about TP53 mutations, such as the presence of a significant number of mutations occurring outside the DNA-binding domain in specific cancer types. We also provide an update on TP53 inherited variants including the ones that should be considered as neutral frequent variations. We thus provide an update of current knowledge on TP53 variations in human cancer as well as inform users on the efficient use of the IARC TP53 Database., (© 2016 WILEY PERIODICALS, INC.)

Background: The nature of somatic mutations observed in human tumors at single gene or genome-wide levels can reveal information on past carcinogenic exposures and mutational processes contributing to tumor development. While large amounts of sequencing data are being generated, the associated analysis and interpretation of mutation patterns that may reveal clues about the natural history of cancer present complex and challenging tasks that require advanced bioinformatics skills. To make such analyses accessible to a wider community of researchers with no programming expertise, we have developed within the web-based user-friendly platform Galaxy a first-of-its-kind package called MutSpec., Results: MutSpec includes a set of tools that perform variant annotation and use advanced statistics for the identification of mutation signatures present in cancer genomes and for comparing the obtained signatures with those published in the COSMIC database and other sources. MutSpec offers an accessible framework for building reproducible analysis pipelines, integrating existing methods and scripts developed in-house with publicly available R packages. MutSpec may be used to analyse data from whole-exome, whole-genome or targeted sequencing experiments performed on human or mouse genomes. Results are provided in various formats including rich graphical outputs. An example is presented to illustrate the package functionalities, the straightforward workflow analysis and the richness of the statistics and publication-grade graphics produced by the tool., Conclusions: MutSpec offers an easy-to-use graphical interface embedded in the popular Galaxy platform that can be used by researchers with limited programming or bioinformatics expertise to analyse mutation signatures present in cancer genomes. MutSpec can thus effectively assist in the discovery of complex mutational processes resulting from exogenous and endogenous carcinogenic insults.

The impact of aircraft noise on health is of growing concern. We investigated the relationship between this exposure and mortality from cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We performed an ecological study on 161 communes (commune being the smallest administrative unit in France) close to the following three major French airports: Paris-Charles de Gaulle, Lyon Saint-Exupéry, and Toulouse-Blagnac. The mortality data were provided by the French Center on Medical Causes of Death for the period 2007-2010. Based on the data provided by the French Civil Aviation Authority, a weighted average exposure to aircraft noise (L den AEI) was computed at the commune level. A Poisson regression model with commune-specific random intercepts, adjusted for potential confounding factors including air pollution, was used to investigate the association between mortality rates and L den AEI. Positive associations were observed between L den AEI and mortality from cardiovascular disease [adjusted mortality rate ratio (MRR) per 10 dB(A) increase in L den AEI = 1.18; 95% confidence interval (CI): 1.11-1.25], coronary heart disease [MRR = 1.24 (1.12-1.36)], and myocardial infarction [MRR = 1.28 (1.11-1.46]. Stroke mortality was more weakly associated with L den AEI [MRR = 1.08 (0.97-1.21]. These significant associations were not attenuated after the adjustment for air pollution. The present ecological study supports the hypothesis of an association between aircraft noise exposure and mortality from cardiovascular disease, coronary heart disease, and myocardial infarction. However, the potential for ecological bias and the possibility that this association could be due to residual confounding cannot be excluded.

Background: Travel practices are changing: bicycle and motorized two-wheeler (MTW) use are rising in some of France's large cities. These are cheaper modes of transport and therefore attractive at a time of economic crisis, but they also allow their users to avoid traffic congestion. At the same time, active transport modes such as walking and cycling are encouraged because they are beneficial to health and reduce pollution. It is therefore important to find out more about the road crash risks of the different modes of transport. To do this, we need to take account of the number of individuals who use each, and, even better, their travel levels., Method: We estimated the exposure-based fatality rates for road traffic crashes in France, on the basis of the ratio between the number of fatalities and exposure to road accident risk. Fatality data were obtained from the French national police database of road traffic casualties in the period 2007-2008. Exposure data was estimated from the latest national household travel survey (ENTD) which was conducted from April 2007 to April 2008. Three quantities of travel were computed for each mode of transport: (1) the number of trips, (2) the distance traveled and (3) the time spent traveling. Annual fatality rates were assessed by road user type, age and sex., Results: The overall annual fatality rates were 6.3 per 100 million trips, 5.8 per billion kilometers traveled and 0.20 per million hours spent traveling. The fatality rates differed according to road user type, age and sex. The risk of being killed was 20 to 32 times higher for motorized two-wheeler users than for car occupants. For cyclists, the risk of being killed, both on the basis of time spent traveling and the number of trips was about 1.5 times higher than for car occupants. Risk for pedestrians compared to car occupants was similar according to time spent traveling, lower according to the number of trips and higher according to the distance traveled. People from the 17-20 and 21-29 age groups and those aged 70 and over had the highest rates. Males had higher rates than females, by a factor of between 2 and 3., Conclusion: When exposure is taken into account, the risks for motorized two-wheeler users are extremely high compared to other types of road user. This disparity can be explained by the combination of speed and a lack of protection (except for helmets). The differential is so great that prevention measures could probably not eliminate it. The question that arises is as follows: with regard to public health, should not the use of MTW, or at least of motorcycles, be deterred? The difference between the fatality risk of cyclists and of car occupants is much smaller (1.5 times higher); besides, there is much room for improvements in cyclist safety, for instance by increasing the use of helmets and conspicuity equipment. Traffic calming could also benefit cyclists, pedestrians and perhaps moped users., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Subgroups of patients registered on a kidney transplant waiting list have higher than usual mortality levels. This study used data from the French Renal Epidemiology and Information Network (REIN) Registry to quantify the impact over time of various comorbidities on the excess risk of death among patients on the waiting list., Methods: Lexis diagrams were used to analyze time since onset of end-stage renal disease and time since registration on the waiting list. The number of excess deaths was calculated by comparison with the number of expected deaths in the general population of the same age and sex., Results: During 45,013 person-years of follow-up, 7,224 patients died, 5,956 (82%) more than expected relative to the general population. There were 101 deaths among wait-listed dialysis patients, 76 more than expected. The excess risk of death increased by 45% per additional year on the waiting list (18-79%, p = 0.0005). Time from end-stage renal disease onset until list registration (p = 0.004), time since registration (p < 0.001), age >65 years (p = 0.008), the presence of a primary renal disease (p = 0.028), and the number of comorbidities (p = 0.035) were independent predictors of death while on the waiting list., Conclusions: The excess risk of death while on the waiting list increased faster in patients with comorbidities. These results require consideration of ways to accelerate access to transplantation in high-risk patients., (© 2013 S. Karger AG, Basel.)