Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

Supplemental folic acid and/or multivitamins in pregnancy is associated with a decreased risk of childhood and adolescent nasopharyngeal carcinoma.

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

Bevacizumab versus placebo in combination with paclitaxel and carboplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase II trial.

BACKGROUND: The value of anti-angiogenesis antibody therapy in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) remains unknown. We carried out a phase II study to evaluate the addition of bevacizumab to paclitaxel plus carboplatin in R/M NPC. MATERIALS AND METHODS: A total of 80 patients with previously untreated R/M NPC were randomly assigned (1 : 1) to CPB or CP groups to receive carboplatin (area under the curve 6) and paclitaxel (175 mg/m2) intravenously every 3 weeks for a maximum of six cycles in combination with or without bevacizumab (7.5 mg/kg), respectively. The primary endpoint was progression-free survival (PFS) as per investigators, and the secondary endpoints were PFS as per independent review committee (IRC), overall survival (OS), objective response rate (ORR), and safety. This study was registered with ClinicalTrials.gov (NCT02250599). RESULTS: The median PFS as per investigators was 7.5 months [95% confidence interval (CI), 6.53-8.45 months] in the CPB group and 6.5 months (95% CI, 5.53-7.52 months) in the CP group (P = 0.148), which were similar to IRC-assessed PFS. The median OS was also alike between CPB and CP arms (21.0 versus 24.7 months; P = 0.326). ORRs were 87.2% and 72.5%, respectively (P = 0.105). However, the tumor-shrinking rate was higher in the CPB arm than in the CP arm (P = 0.035). No differences in grade 3 or higher adverse events between the groups were observed. CONCLUSIONS: Addition of bevacizumab to paclitaxel plus carboplatin as first-line treatment did not prolong PFS and OS in patients with R/M NPC but improved tumor-shrinking rate. These results indicated that bevacizumab plus chemotherapy might be an optional choice for NPC with heavy tumor load or those pursuing short-term efficacy in neoadjuvant and concurrent chemotherapy.

Association of Ambient Air Pollution with Nasopharyngeal Carcinoma Incidence in Ten Large Chinese Cities, 2006-2013.

Large cities in China are experiencing severe ambient air pollution. Although China accounts for more than 45% of new cases of nasopharyngeal carcinoma worldwide in 2018, few studies have examined the association between ambient air pollution and the high nasopharyngeal carcinoma (NPC) incidence in China. Thus, we aim to investigate whether exposure to ambient air pollution (including nitrogen dioxide, sulfur dioxide, and PM10) would significantly affect NPC incidence in large Chinese cities. We collected panel data of ten Chinese provincial cities about local NPC incidence, air pollution level, meteorology, and city profiles during 2006 to 2013 to construct a two-way fixed-effects model to explore the association between ambient air pollution and NPC incidence, as well as possible regional and gender differences behind the association. We found that NO2 had the strongest association with NPC incidence, and the relative risks were 2.2995 (95% CI, 1.2567-4.2075) for males and 1.3010 (95% CI, 0.8212-2.0620) for females, respectively. Under cumulative exposure, it was still NO2 that had the strongest association with NPC incidence, with a relative risk of 1.8836 (95% CI, 1.2416-2.8577), compared to 1.0857 (95% CI, 0.9474-1.2450) and 1.0547 (95% CI, 0.8790-1.2663) for SO2 and PM10, respectively. In addition, males were found more sensitive to ambient air pollution than females. We also found that southern Chinese cities were more sensitive to NO2 than northern cities, which might be related to a higher humidity there. Our study reveals that exposure to ambient air pollutants like SO2, PM10, and particularly NO2, is significantly positively associated with NPC incidence in China.

Occupational exposure to volatile organic compounds and health risks in Colorado nail salons.

Nail salon technicians face chronic exposure to volatile organic compounds (VOCs), which can lead to adverse health outcomes including cancer. In this study, indoor levels of formaldehyde, as well as benzene, toluene, ethylbenzene and xylene, were measured in 6 Colorado nail salons. Personal exposure VOC measurements and health questionnaires (n = 20) were also performed; questionnaires included employee demographics, health symptoms experienced, and protective equipment used. Cancer slope factors from the United States Environmental Protection Agency (US EPA) and anthropometric data from the Centers for Disease Control and Prevention were then used to estimate cancer risk for workers, assuming 20-yr exposures to concentrations of benzene and formaldehyde reported here. Results show that 70% of surveyed workers experienced at least one health issue related to their employment, with many reporting multiple related symptoms. Indoor concentrations of formaldehyde ranged from 5.32 to 20.6 µg m-3, across all 6 salons. Indoor concentrations of toluene ranged from 26.7 to 816 µg m-3, followed by benzene (3.13-51.8 µg m-3), xylenes (5.16-34.6 µg m-3), and ethylbenzene (1.65-9.52 µg m-3). Formaldehyde levels measured in one salon exceeded the Recommended Exposure Limit from the National Institute for Occupational Safety and Health. Cancer risk estimates from formaldehyde exposure exceeded the US EPA de minimis risk level (1 × 10-6) for squamous cell carcinoma, nasopharyngeal cancer, Hodgkin's lymphoma, and leukemia; leukemia risk exceeded 1 × 10-4 in one salon. The average leukemia risk from benzene exposure also exceeded the US EPA de minimis risk level for all demographic categories modeled. In general, concentrations of aromatic compounds measured here were comparable to those measured in studies of oil refinery and auto garage workers. Cancer risk models determined that 20-yr exposure to formaldehyde and benzene concentrations measured in this study will significantly increase worker's risk of developing cancer in their lifetime.

Occupational exposure to wood dust and risk of nasopharyngeal cancer: A systematic review and meta-analysis.

INTRODUCTION: Nasopharyngeal cancer (NPC) is one of the most commonly occurring cancers in some regions. While wood dust is a confirmed human carcinogen, its association with NPC remains uncertain due to inconsistent findings in the related studies. We performed the first systematic review and meta-analysis on the epidemiological evidence to examine the association between occupational exposure to wood dust and the risk of NPC. METHODS: In this meta-analysis study, the PubMed and Scopus databases were searched for English-language publications. seven case-control studies were included in the pooled analysis. RESULTS: These studies were published between 1991 and 2016. The heterogeneity across the studies was significant (P = 0.06, I2 = 50.4%). The results of the random effects model meta-analysis showed that there was a direct relationship between occupational exposure to wood dust and NPC (OR = 1.5 95% CI: 1.09-2.07). Among different histological subtypes of NPC, there was a significantly increased risk for the nonkeratinizing carcinoma following wood dust exposure (OR = 1.68, 95%CI: 1.03-2.74). We found no evidence of publication bias across studies according to the result of the Egger's test (P of bias = 0.073). CONCLUSIONS: This meta-analysis suggests that occupational exposure to wood dust can be associated with an increased risk of the nonkeratinizing carcinoma of the histological subtypes of nasopharyngeal cancer.

Occupational exposure to wood dust and risk of nasal and nasopharyngeal cancer: A case-control study among men in four nordic countries-With an emphasis on nasal adenocarcinoma.

The current study aims to provide stronger evidence to aid in our understanding of the role of cumulative occupational exposure to (softwood-dominated) mixed wood dust in aetiology of nasal cancer. We included broad exposure occurred in a range of wood-processing occupation across varied industries in four Nordic countries. A population-based case-control study was conducted on all male cases with nasal adenocarcinoma (393 cases), other types of nasal cancer (2,446) and nasopharyngeal cancer (1,747) diagnosed in Finland, Sweden, Norway and Iceland between 1961 and 2005. For each case, five male controls, who were alive at the time of diagnosis of the case (index date), were randomly selected, matched by birth-year and country. Cumulative exposures (CE)s to wood dust and formaldehyde before the index date were quantified based on a job-exposure matrix linked to occupational titles derived from population censuses. Hazard ratios (HRs) for the CE of wood dust were estimated by conditional logistic regression, adjusted for CE to formaldehyde and 95% confidence intervals (CIs) were calculated. There was an increasing risk of nasal adenocarcinoma related to wood dust exposure. The HR in the highest CE category of wood dust (≥ 28.82 mg/m3 -years) was 16.5 (95% CI 5.05-54.1). Neither nonadenocarcinoma of the nose nor nasopharyngeal cancer could be linked to wood dust exposure. CE to softwood-dominated mixed wood dusts is strongly linked with elevated risk in nasal adenocarcinoma but not with other types of nasal or nasopharyngeal cancer.

Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network.

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, ß-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer.

The bottom-up approach to bounding potential low-dose cancer risks from formaldehyde: An update.

In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the background cancer risk and the background (endogenous) concentration of a cancer-related exposure biomarker in specific target tissues. After allowing for statistical uncertainty in these two parameters, the ratio of the background risk to background exposure provides a conservative slope factor estimate that can be utilized to bound the added risk that may be associated with incremental exogenous exposures. Our original bottom-up estimates were markedly smaller than those obtained previously by the US Environmental Protection Agency (USEPA) with a conventional top-down approach to modeling nasopharyngeal cancer and leukemia mortality data from a US worker cohort. Herein we provide updated bottom-up estimates of risk for these two cancers that are smaller still, and rely upon more robust estimates of endogenous and exogenous formaldehyde-DNA adducts in monkeys and a more robust estimate of the DNA adduct elimination half-life in rats, both obtained very recently. We also re-examine the worker mortality data used by USEPA in developing its estimate of human leukemia incidence from lifetime exposure to 1 ppm airborne formaldehyde. Finally, we compare a new bottom-up slope estimate of the risk of rat nasal cancer with conventional top-down estimates obtained with empirical dose-response modeling of rat nasal cancer bioassay data.

Clusterin induced by N,N'-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis.

Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N'-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through up-regulating anterior clusterin (CLU). DNP was found to increase CLU, matrix metalloproteinases (MMP) 9 and vascular endothelial growth factor (VEGF) expression and activity, further DNP-increased MMP-9 and VEGF expression was through up-regulating CLU. We also found that DNP increased the binding of CLU with MMP-9 or VEGF. DNP induced the motility and invasion of NPC cell, which was inhibited by siRNA-CLU. The clinical investigation showed that CLU, MMP-9 and VEGF were positively correlated with the tumor-node -metastasis (TNM) classification. These results indicate that DNP may promote NPC tumor metastasis through up-regulating CLU, MMP-9 and VEGF expression. Therefore, DNP-increased CLU expression may be an important factor of NPC-high metastasis, and CLU may serve as a biomarker for NPC metastasis.

Household inhalants exposure and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China.

BACKGROUND: Epidemiological studies show that cigarette smoking increase the risk of nasopharyngeal carcinoma (NPC), however, whether other common, potentially adverse household inhalants increase NPC risk remains uncertain. METHODS: We conducted a large case-control study to explore the effects of household inhalants, such as incense, mosquito coil, cooking fumes, and wood combustion, on NPC risk. We recruited 1,845 cases and 2,275 controls from Guangdong province, a high-risk area for NPC in China, to obtain the demographic data and relevant exposure information through face-to-face interviews. RESULTS: We found that incense burning was associated with NPC risk by comparing frequent incense use with never using incense [OR and 95% confidence interval (CI) = 1.73, (1.43, 2.09)]. Wood fuel use was also associated with NPC risk compared with non-wood fire use [OR and 95% CI = 1.95, (1.65, 2.31)]. More intriguingly, we observed a significant addictive interaction between frequent incense burning and heavy cigarette smoking on NPC risk [synergistic index (SI) = 1.67; 95% CI: 1.01, 2.76]. We also found a significant joint effect between wood fuel use and NPC family history for NPC risk (SI = 1.77; 95% CI: 1.06, 2.96). However, neither mosquito oil nor cooking fumes were associated with NPC risk. CONCLUSIONS: Our study shows that incense smoke is not only the potential independent risk factor but also co-contributes with cigarette smoking to NPC risk. Moreover, wood combustion is another potential environmental risk factor and exerts a joint effect with NPC family history on NPC.

Blood cadmium burden and the risk of nasopharyngeal carcinoma: a case-control study in Chinese Chaoshan population.

Cadmium is a ubiquitous carcinogenic pollutant with multiple biological effects. Both observational and experimental studies have suggested associations between cadmium and the rates of many types of cancers. The aim of the present study was to evaluate whether cadmium exposure is associated with nasopharyngeal carcinoma (NPC) in a population with a relatively high prevalence in southeast China. Hospital-based 134 NPC cases and 132 cancer-free controls were recruited from a cancer hospital in Chaoshan area, southeast of China. Basic clinical data and information of lifetime styles, smoking, and drinking as well as other demographic characteristics were also collected from medical records. Blood cadmium levels (BCLs) were detected by graphite-furnace atomizer absorption spectrophotometer (GFAAS). BCLs and over-limit ratios between cases and controls were compared. The relationships between BCLs and NPC were explored by comparing BCLs differences between/among different characteristics of related factors and logistic regression analysis. In addition, BCLs within cases were also compared in relation to the disease clinical stages, pathological types, and metastasis. The median concentration of blood cadmium in cases (3.84, interquartile range 2.21-6.10) was significantly higher than that of controls (2.28, interquartile range 1.79-3.45). The over-limit ratio (≥5 µg/L) in cases was also higher than that in controls (35.1 vs. 13.6%, χ(2) = 16.55, p < 0.001). Smokers tended to have high levels of cadmium burden, and smokers with longer smoking pack-years in cases had relatively higher BCLs (p = 0.001). NPC patients with diseases history presented lower cadmium burden (p = 0.020). In the NPC cases, BCLs were positively associated with clinical stages and N classification (r = 0.193, 0.187, respectively, p < 0.05). Cadmium seems to be a risk factor of NPC, and high cadmium exposure may promote the occurrence and development of NPC.

Angiofibroma nasofaríngeo juvenil con extensión orbitaria / Juvenile nasopharyngeal angiofibroma with orbital extension

CASO CLÍNICO: Varón de 21 años con historia de exoftalmos izquierdo y diplopía de 2 semanas de evolución. La resonancia magnética mostró una lesión muy vascularizada etmoido-orbitaria con invasión de base del cráneo anterior y extensión orbitaria. La biopsia etmoidal confirmó un tejido fibrovascular compatible con angiofibroma. DISCUSIÓN: El angiofibroma nasofaríngeo juvenil (ANJ) es un tumor benigno con características locales de malignidad debido a su capacidad de invadir áreas adyacentes. En nuestro caso, el comienzo se presenta con manifestaciones de extensión orbitaria. Consideramos necesario un conocimiento amplio y un abordaje multidisciplinario con el fin de mejorar el pronóstico

CLINICAL CASE: The case is presented of a 21 year-old male with a history of left proptosis and diplopia of two weeks of onset. The MRI showed an ethmoid-orbital vascular lesion with anterior skull base invasion and orbital extension. Biopsy of the ethmoid confirmed fibrovascular tissue, which supported the diagnosis of angiofibroma. DISCUSSION: It is a benign neoplasm with local characteristics of malignancy due to its ability to invade adjacent areas. In this case, the debut presented with manifestations of orbital extension. A broad and multidisciplinary approach is needed in order to improve prognosis

Cadmium and nickel in blood of Tunisian population and risk of nasosinusal polyposis disease.

Nasosinusal polyposis (NSP) is a chronic inflammatory disease of the nasal mucosa. Although the pathophysiology underlying NSP formation is not fully understood, environmental factors appear to be contributed the development of this disease. A case-control study of Tunisian patients was examined to assess the levels of cadmium (Cd) and nickel (Ni) in blood and reparse the association between the exposure to these metals and the risk of nasosinusal polyposis disease. Mean blood levels of Cd in patients (2.2 ± 12.8 µg/L) were significantly higher than those of controls (0.5 ± 0.7 µg/L). Levels of blood Cd were positively correlated with tobacco smoking and chewing among controls. The Cd and Ni concentrations among control (p = 0.001) and patient (p = 0.018) tobacco consumers (smoking, chewing, and shisha) were significantly higher than those nonconsumers. Additionally, Ni blood levels of patient and control smokers were significantly higher than those of nonsmokers. Cd levels in blood samples of NSP patients occupationally exposed for more than 14 years were eight times higher than that of nonexposed. Drinking water was also found to be incriminated as exposure sources. Among risk factors, shisha consumption, environmental exposure, and occupational exposure presented the most significant association with NSP disease (odds ratio (OR) = 14.1, 10.1, and 1.7, respectively). High levels of blood Cd (OR = 3.5) were strongly associated with NSP disease (p = 0.027). Ni blood levels were shown to be associated with the four stages of polyps in both nasal cavities (right and left) (p < 0.05). This investigation suggested a potential role of toxic metals in the mechanism of NSP disease development. Exposure assessment investigations encompassing a wider population are needed.

Domestic incense burning and nasopharyngeal carcinoma: a case-control study in Hong Kong Chinese.

Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control study and case-only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure-response effect. Evidence for gene-environment interactions supported the knowledge that NPC is a multi-factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility.

Mortality from lymphohematopoietic neoplasms and other causes in a cohort of laminated plastic workers exposed to formaldehyde.

PURPOSE: A possible relationship between exposure to formaldehyde and leukemia-particularly myeloid leukemia-as well as of lymphoid neoplasms has been debated and is still controversial. We thus examined the issue using data from a cohort of workers of a laminated plastic factory sited in Piedmont, northern Italy. METHODS: The study cohort included 2,750 subjects (2,227 men and 523 women) who worked in the factory between 1947 and 2011, for at least 180 days. Follow-up ended in May 2011, for a total of 70,933 person-years of observation. We computed standardized mortality ratios (SMR) and 95% confidence intervals (CI) using national and (whenever available) Piedmont Region death rates. RESULTS: Overall, there were 417 deaths versus 493.4 expected ones (SMR = 84.5, 95% CI 76.6-93.0). The SMRs were 79.8 (95% CI 67.5-93.6) for total cancer mortality, 148.5 (95% CI 68.0-282.2) for oral cavity and pharynx (three deaths were registered, but not confirmed, as nasopharyngeal cancer), 48.3 (95% CI 13.1-123.7) for pancreas, 66.1 (95% CI 13.6-193.0) for larynx, and 96.7 (95% CI 72.0-127.2) for lung cancer. The SMR of all lymphohematopoietic malignancies was 68.6 (95% CI 31.4-130.3; nine observed deaths). This tended to increase with duration of exposure and to decrease with period at first exposure, always remaining below 100. There were four deaths from lymphoma (SMR = 74.1, 95% CI 20.1-189.6) and five deaths from leukemia (SMR = 92.4, 95% CI 29.9-215.3). CONCLUSIONS: We found no meaningful excess mortality from any lymphohematopoietic nor other neoplasms, except possibly for nasopharyngeal cancer.

Dysfunction of mitochondria due to environmental carcinogens in nasopharyngeal carcinoma in the ethnic group of Northeast Indian population.

Nasopharyngeal carcinoma (NPC) is a rare cancer worldwide, but in India, NPC is uncommon in its subcontinent except in the north-eastern part of the country. NPC is thought to be caused by the combined effects of environmental carcinogens, genetic susceptibility and Epstein-Barr virus (EBV). This is the first study that aimed to examine the selected risk factors, mostly dietary, viral environmental, metabolic gene polymorphisms, mitochondrial DNA (mtDNA) copy number variation and their risk, in subjects who are highly prone to NPC in the ethnic groups of Northeast India, which has included cases, first-degree relatives and controls. The cases and controls were selected from three ethnic groups (Manipuri, Naga and Mizo) of Northeast India with high prevalence of NPC. This case-control family study includes 64 NPC patients, 88 first-degree relatives and 100 controls having no history of cancer. PCR-based detection was done for EBV-latent membrane protein 1 (LMP1) gene and glutathione S-transferase Mu 1 (GSTM1)-glutathione S-transferase theta 1 (GSTT1) polymorphism. A comparative ΔCt method was used for the determination of mtDNA content. An increased risk of 2.00-6.06-folds to NPC was observed with those who intake smoked meat and fish, salted fish and fermented fish; betel nut chewers; tobacco smokers; alcohol drinkers; and those who have kitchen inside the living room, glutathione S-transferase null genotype and EBV infection. The risk of NPC increased in cases with decreased mtDNA copy number (P trend = 0.007). A significant difference between GST null genotypes and EBV infection with mtDNA content was found in the cases (P < 0.0001). The understandings of environment-genetic risk factors and their role in the etiology of NPC are helpful as preventive measures and screening.

Upper airway cancer, myeloid leukemia, and other cancers in a cohort of British chemical workers exposed to formaldehyde.

The International Agency for Research on Cancer controversially has classified formaldehyde as causing nasopharyngeal carcinoma and myeloid leukemia. To provide further information on this question, we extended follow-up of a cohort of 14,008 chemical workers at 6 factories in England and Wales, covering the period 1941-2012. Mortality was compared with national death rates for England and Wales, and associations with incident upper airway cancer and leukemia were explored in nested case-control analyses. We observed excess deaths from cancers of the esophagus (100 observed vs. 93.1 expected), stomach (182 vs. 141.4), rectum (107 vs. 86.8), liver (35 vs. 26.9), and lung (813 vs. 645.8), but none of these tumors exhibited a clear exposure-response relationship. Nested case-control analyses of 115 men with upper airway cancer (including 1 nasopharyngeal cancer), 92 men with leukemia, and 45 men with myeloid leukemia indicated no elevations of risk in the highest exposure category (high exposure for ≥1 year). When the 2 highest exposure categories were combined, the odds ratio for myeloid leukemia was 1.26 (95% confidence interval: 0.39, 4.08). Our results provide no support for an increased hazard of myeloid leukemia, nasopharyngeal carcinoma, or other upper airway tumors from formaldehyde exposure. These results indicate that any excess risk of these cancers, even from relatively high exposures, is at most small.

Historical long-term exposure to pentachlorophenol causing risk of cancer--a community study.

BACKGROUND: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) might contribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancer risk at the community level. OBJECTIVE: The present study was to explore the cancer risk for the community population living long-term in a PCP contaminated area. METHODS: All the cancer cases diagnosed in 2009- 2011 in Tongling City were collected. The cancer patients' residencies were geo-referenced in each district. The historical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was further used to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied to detect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationship between PCP pollution and cancer incidence. RESULTS: A total of 5,288 cancer cases (3,451 male and 1,837 female) were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and with cancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the low exposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61, 95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevated and exposure time extended. CONCLUSION: The present study found that community residents living in the PCP contaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophageal cancers are most possibly associated with PCP exposure.