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PubMed2005

Occupational risk factors for kidney cancer: a cohort study in Sweden.

Although many studies have examined the associations between occupational exposures and kidney cancer, the evidence is not consistent. To examine the risk of occupational exposures on kidney cancer, we carried out a follow-up study on the economically active Swedish population, based on the latest update of the Swedish Family-Cancer Database. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CIs) for different occupational groups, adjusted for age, period, and socioeconomic status. The reference group was all the economically active population. An increased risk of renal parenchymal cancer was observed for miners and quarry workers, drivers, sales agents, transport workers, and public safety and protection workers among men, and launderers and dry cleaners among women. Significantly increased SIRs of renal pelvical cancer were also observed for the food manufacture workers among men, and journalists and shoe and leather industry workers among women. Male forestry workers, smelters, and metal foundry workers had increased risk for unspecified kidney cancer. Although smoking may explain some of these results, exposure to gasoline, diesel, their exposure products, some metal and chemicals in shoe and leather works, and dry-cleaning products may be associated with kidney cancer.

Confidence Intervals↗
PubMed2003

Gene profiling and promoter reporter assays: novel tools for comparing the biological effects of botanical extracts on human prostate cancer cells and understanding their mechanisms of action.

The use of botanical mixtures is commonplace in patients with prostate cancer, yet the majority of these products have not been rigorously tested in clinical trials. Here we use PC-SPES, a combination of eight herbs that has been shown to be effective in clinical trials in patients with prostate cancer, as a model system to demonstrate 'proof of principle' as to how gene expression profiling coupled with promoter assays can evaluate the effect of herbal cocktails on human prostate cancer. In addition, we demonstrate how such approaches may be used for standardization of herbal extract activity by comparing the gene profile of PC-SPES with that of PC-CARE, a product with a similar herbal composition. Since prior studies have shown that PC-SPES contains estrogenic organic compounds, and such compounds are known to affect prostate cancer, an important issue is whether these are the primary drivers of the gene profile. Our data suggest that gene expression profiles of LNCaP human prostate cancer cells in response to PC-SPES are different from those found when diethylstilbestrol (DES), a synthetic estrogen, is used, suggesting that the estrogenic moieties within PC-SPES do not drive this expression signature. In contrast, the expression profile of PC-CARE was almost identical to that of DES, highlighting that mixtures containing similar herbal compositions do not necessarily result in similar biological activities. Interestingly, these three agents cause similar in vitro morphological changes and growth effects on LNCaP. To validate the expression profiling data, we evaluated the protein expression and promoter activity of prostate-specific antigen (PSA), a gene induced by PC-SPES but repressed by DES. In order to gain a mechanistic understanding of how PC-SPES and DES affect PSA expression differently, LNCaP cells were transiently transfected with wild-type and mutagenized PSA promoter, ARE concatemers and appropriate controls. We provide evidence that androgen response elements (ARE) II and III within the promoter region are responsible for the suppressive effects of DES and stimulatory effects of PC-SPES. In addition, we show that the effects on PSA transcription are ARE specific in the case of DES while PC-SPES affects this promoter nonspecifically. In conclusion, expression profiling coupled with mechanistic target validation yield valuable clues as to the mode of action of complex botanical mixtures and provides a new way to compare objectively mixtures with similar components either for effect or quality assurance prior to their use in clinical trials.

Adenocarcinoma↗
PubMed1995

Occupational associations with lung cancer in two Ontario cities.

A death certificate based case-control study of lung cancer in two Ontario cities was performed to estimate the risk of lung cancer attributable to occupation in Ontario, and to estimate the proportion of occupational lung cancers receiving compensation from the Workers' Compensation Board. Occupation and industry were identified from the death certificate. A priori occupations for analysis were those whose members had received compensation for occupational cancer from the Ontario Workers' Compensation Board. Population attributable risks were computed using the relative risks observed in this study and employment data from the 1986 Census of Canada. Subjects were all men (N = 967) between the ages of 45 and 75 years resident in the cities of Hamilton and Sault Ste-Marie who died of lung cancer from 1979 to 1988. Controls (2,821) were matched on age, year of death, and city of residence. In agreement with other studies, an increased risk of lung cancer was observed for workers in the construction sector, for miners, and for truck drivers. It was estimated that only a small proportion of lung cancers attributable to occupation are compensated in Ontario. It is believed that many occupational cancers go uncompensated because of the failure to file claims, rather than because claims are rejected by Compensation Boards. Physicians are in a position to advise patients about the possibility of compensable disease and to act as advocates for them. By recognizing compensable illness, physicians have the opportunity to ease the financial burden of patients and their families. The challenge is a difficult one, but it is well worth pursuing.

Aged↗
PubMed2004

Risk of esophageal, ovarian, testicular, kidney and bladder cancers and leukemia among finnish workers exposed to diesel or gasoline engine exhaust.

Occupational exposure to diesel exhaust has been classified as probably carcinogenic and that to gasoline engine exhaust as possibly carcinogenic to humans. Earlier results concerning cancers other than lung cancer are scarce and inconsistent, and exposure-response relations have seldom been reported. We followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person-years during 1971-1995. Incident cases of esophageal cancer (n = 2,198), ovarian cancer (5,082), testicular cancer (387), kidney cancer (7,366), bladder cancer (8,110) and leukemia (4,562) were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to diesel and gasoline engine exhausts with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as product of prevalence, level and estimated duration of exposure. The relative risk (RR) of cancer for exposure categories in relation to the unexposed group was calculated using the Poisson regression model and adjusted for confounders. An increasing RR for ovarian cancer was observed with the increasing CE of diesel exhaust (p for trend = 0.006). The RR in the highest CE category was 3.69 (95% CI = 1.38-9.86). For gasoline engine exhaust, the RR was significantly increased only in the middle CE category (1.70; 95% CI = 1.11-2.62). Slight elevations of RR for bladder and kidney cancers were found at the lowest exposure level of engine exhausts, largely attributable to drivers. No effect of the exposures was observed for the other cancers. This study suggests an exposure-response relation between diesel exhaust and ovarian cancer.

Aged↗
PubMed1995

Driving ability in cancer patients receiving long-term morphine analgesia.

When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

Administration, Oral↗
PubMed2018

Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

OXPHOS↗
PubMedDate not supplied

A case-control study of renal cell carcinoma in relation to occupation, smoking, and alcohol consumption.

A case-control study based on data from a cancer registry was conducted to evaluate the effects of smoking, alcohol use, and occupation on renal cell cancer risk. Information was obtained for 326 male and female cases and 978 age- and sex-matched controls. Elevated risks were identified for cigarette smokers and for men employed as truck drivers. No relationship between alcohol consumption and renal cancer was observed.

Adult↗
PubMed2004

Occupation and bladder cancer risk in a population-based case-control study in New Hampshire.

OBJECTIVE: To identify occupations with excess bladder cancer risk in New Hampshire, where bladder cancer mortality rates have been elevated for decades. METHODS: Lifetime occupational histories were obtained from interviews with 424 cases and 645 controls in a population-based case-control study. Unconditional logistic regression models were used to estimate odds ratios (Ors) and 95% confidence intervals (CI) for each occupation, adjusted for age and smoking. Analyses by duration of employment were carried out and interactions with smoking were examined. RESULTS: Male tractor-trailer truck drivers had an elevated risk for bladder cancer (OR = 2.4, CI = 1.4-4.1), with a significant positive trend in risk with increasing duration of employment (P (trend) = 0.0003). Male metal/plastic processing machine operators also had a significant excess (OR = 4.9, CI = 1.6-15.1), attributable mainly to molding/casting machine operators (OR = 16.6, CI = 2.1-131). Elevated risk was also observed for male fabricators, assemblers, and hand workers (OR = 1.8, CI = 1.0-3.4). Women in certain sales occupations (sales clerks, counter clerks, and cashiers) had a significant excess risk (OR = 2.2, CI = 1.3-3.9) and a significant trend with duration of employment (P (trend) = 0.016), as did female health service workers (OR = 4.1, CI = 1.6-10.7; P (trend) = 0.014). There was a positive interaction between smoking and employment as a health service worker (p = 0.036). CONCLUSIONS: These findings are generally consistent with previous studies. Elevated risks for male molding/casting machine operators, female salesworkers, and female health service workers, especially those with a history of smoking, require further investigation.

Adult↗
PubMed1996

Occupational exposure to 60-hertz magnetic fields and risk of breast cancer in women.

We used data from a large population-based case-control study to test the hypothesis that women whose "usual occupation" entailed exposure to higher than background 60-Hz magnetic fields had a higher risk of breast cancer than women without such exposure. Breast cancer cases were identified from four statewide tumor registries, and controls were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on usual occupation and breast cancer risk factors was obtained by telephone interview. We calculated adjusted odds ratios from logistic regression models for women holding occupations with potential for low, medium, or high magnetic field exposure, compared with background exposure. There was a modest increase in risk for women with potential for high exposure [odds ratio (OR) = 1.43; 95% confidence interval (CI) = 0.99-2.09], and no increase for women with potential for medium (OR = 1.09; 95% CI = 0.83-1.42) or low (OR = 1.02; 95% CI = 0.91-1.15) exposure The risk among premenopausal women in the highest-exposure category was higher (OR = 1.98; 95% CI = 1.04-3.78) than for postmenopausal women (OR = 1.33; 95% CI = 0.82-2.17).

Breast Neoplasms↗
PubMed1994

Early adulthood physical activity and colon cancer risk among Wisconsin women.

Frequency of strenuous activity during ages 14-22 was ascertained retrospectively from 536 Wisconsin women with newly reported diagnoses of colon cancer and 2315 controls randomly selected from Wisconsin driver's license and Medicare beneficiary lists. Thirty-five % of cases and 34% of controls reported strenuous activity during this period of early adulthood. After adjusting for age, family history of large bowel cancer, history of screening sigmoidoscopy, and body mass index in logistic regression models, women who reported any strenuous activity were at a similar risk of colon cancer as women who did not report activity [odds ratio (OR), 1.02; 95% confidence interval (CI), 0.82-1.27); no significant decrease in risk was seen with increase in frequency of activity (P for trend = 0.84). Results were similar for the right and left colon subsites. These data suggest that early adulthood physical activity may not confer the same protective effect that has been observed with recent physical activity.

Age Factors↗
PubMed1988

Validation of body size information on driver's licenses.

Weight and height values measured in a population-based case-control study of breast cancer conducted in Hawaii were used to validate body size information recorded on driver's licenses. It is concluded that this information is sufficiently accurate to justify the use of driver's license registration files as a means of assembling large prospective or historical cohorts to study the health hazards of obesity.

Adult↗
PubMed2000

An audit of subcutaneous syringe drivers in a non-specialist hospital.

The use of syringe drivers as a method of drug delivery to control symptoms in palliative care is a common and accepted practice, but one which has evolved rather than been subject to close multiprofessional scrutiny and guideline formation. There is evidence that adverse incidents may arise as a result of syringe driver use (Medical Devices Agency (MDA), 1998), for example, errors in drug calculations, drug stability, equipment failure (including disconnection) and the wrong rate of infusion. Inadequate user training, poor servicing of equipment and inadequate documentation and record keeping are all thought to be contributing factors (MDA, 1998). In the hospital where this audit was carried out, syringe drivers are used to administer drugs to patients with cancer during the palliative phase of illness. The purpose of this clinical audit was to establish the standard of current practice in wards where syringe drivers were being used. A retrospective study of 13 cases of syringe driver use is presented. The results highlight many areas of unregulated practice with regard to setting up, monitoring and maintenance of syringe drivers. The choice of drugs and doses prescribed, evaluation of treatment responses and review of treatment regimens were also areas of concern. Guidelines for the use of syringe drivers in non-specialist hospitals are put forward.

Adult↗
PubMed1990

Case-control study of lung cancer and truck driving in the Teamsters Union.

We conducted a case-control study of lung cancer deaths in the Teamsters Union to compare the risk of different occupations within the teamsters, after controlling for smoking and other confounders. Occupations with no presumed exposure to diesel fumes were used as the nonexposed group. The study population consisted of 996 cases and 1,085 controls who had died in 1982-83 after applying for pensions. Next of kin provided information on smoking, work history, and other potential confounders. Work history data were also obtained from the Teamsters Union. While no single job category had a significant excess risk compared to the non-exposed group, certain sub-groups were elevated. The odds ratio for those with long-term employment as long-haul truckers after 1959 (an approximate date for the introduction of diesel engines) was 1.55 (95% CI: 0.97, 2.47). Long-term drivers of primarily diesel trucks had an odds ratio of 1.89 (95% CI: 1.04, 3.42). Overall, our results suggest that diesel truck drivers have an excess risk of lung cancer compared to other teamsters in jobs outside the trucking industry. However, our findings were not uniformly consistent and our data have many limitations, the most important of which is the lack of data on exposure to diesel fumes.

Automobile Driving↗
PubMed2006

Update of mortality and cancer incidence in the Australian petroleum industry cohort.

OBJECTIVES: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry. METHODS: Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16,547 males and 1356 females was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. RESULTS: There was a significant elevation of the incidence of mesothelioma (SIR 1.77, 95% CI 1.05 to 2.79), melanoma (SIR 1.37, 95% CI 1.19 to 1.58), and prostate cancer (SIR 1.18, 95% CI 1.04 to 1.34). The SIRs of all leukaemias and of acute non-lymphocytic leukaemia (ANLL) were not significantly different from unity, but all 11 ANLL cases were clustered in the middle to high hydrocarbon exposure categories. Tanker drivers had a significantly elevated incidence of kidney cancer (12 cases v 5.84 expected, SIR 2.05, 95% CI 1.06 to 3.59). Lung cancer incidence was significantly reduced (SIR 0.69, 95% CI 0.57 to 0.83) CONCLUSIONS: Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. No occupational cause has been identified for the excess of melanoma, or prostatic or bladder cancer. The possibility of a causal relationship between cancer of the kidney and hydrocarbon exposure warrants further study. It is uncertain whether benzene exposures, particularly past levels of exposure, have been high enough to cause ANLL.

Australia↗
PubMed2026

Co-Occurring EGFR L858R Mutation and HER2 Amplification in NSCLC Identified by Stepwise Molecular Profiling.

BACKGROUND The coexistence of multiple oncogenic drivers in non-small cell lung cancer (NSCLC) is a rare and diagnostically challenging molecular configuration. Conventional polymerase chain reaction (PCR)-based testing may fail to detect co-occurring genomic alterations, potentially limiting therapeutic options, particularly in resource-constrained settings. CASE REPORT We describe the case of a 54-year-old non-smoking woman diagnosed with Stage IIIA lung adenocarcinoma in 2020. Initial PCR-based molecular testing was negative for EGFR mutations. Following disease progression with brain metastases and severe chemotherapy toxicity, stepwise molecular profiling in a resource-limited setting identified HER2 (ERBB2) amplification via fluorescence in situ hybridization (FISH). The patient achieved 23 months of clinical and radiological stabilization on trastuzumab. Subsequent next-generation sequencing (NGS) analysis of archived tissue revealed a previously undetected estimated glomular filtration rate (EGFR) L858R mutation. In late April 2025, new lesions appeared in the lungs, indicating disease progression. Based on the previously verified EGFR L858R mutation, the treatment strategy was revised and gefitinib was initiated in May 2025. CONCLUSIONS This case illustrates that co-occurring EGFR and HER2 alterations can remain undetected following initial limited molecular testing, and that stepwise molecular profiling in a resource-constrained setting can facilitate identification of therapeutically actionable targets. The sequential clinical responses observed are consistent with the biological relevance of both alterations, although broader conclusions regarding diagnostic strategy or driver hierarchy cannot be drawn from a single observation.

Humans↗
PubMed1991

The Occupational Cancer Incidence Surveillance Study (OCISS): risk of lung cancer by usual occupation and industry in the Detroit metropolitan area.

This case-referent study assesses occupational risk factors associated with lung cancer, utilizing colon and rectum cancer referents. Complete occupational and tobacco use histories were obtained by telephone interview for 5,935 incident lung cancer cases and 3,956 incident colon and rectum cancer referents. The analysis included 43 usual occupational groups and 48 usual industry groups comprised of at least 10 cases. Among all cases, there were significant elevated risks for excavating and mining workers (OR = 4.01), furnace workers (OR = 3.11), armed services personnel (OR = 3.10), agricultural workers (OR = 2.05), driver sales (OR = 2.21), mechanics (OR = 1.72), painters (OR = 1.96), and drivers (OR = 1.88). Industries with significant elevated lung cancer risk included farming (OR = 2.21), mining (OR = 2.98), and primary ferrous metals manufacturing (OR = 2.43). Analyses of white and black men separately revealed that the excess of lung cancer among mechanics is restricted to black males (OR = 4.16). The risk of lung cancer among armed services personnel is higher among black men (OR = 10.54) than among white men (OR = 3.06). Five of the occupations observed more often among lung cancer cases have probable exposure to diesel exhaust.

Adult↗
PubMed2026

Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer.

We performed an integrated clinical and genomic analysis of over 7,000 consecutively sequenced colorectal cancer (CRC) samples to comprehensively characterize genetic drivers and metastatic tropisms of CRC. We find that genomic evolutionary changes, such as clonal mutations and oncogenic mutant allelic imbalance, selectively enhance the impact of recurrent oncogenic alterations. We identify the relative timing of organ-specific metastasis, showing sequential metastatic progression in microsatellite stable CRC with brain and adrenal metastases as late events; metastatic sites that cluster together, such as lung, bone, and brain metastases; and genomic events that enhance or decrease risk for each metastatic site, with WNT pathway activation as overall protective while RAS pathway activation increased risk for spread to all metastatic sites. Our data suggest that despite the heterogeneity in CRC, genomic evolution increases the impact of recurrent alterations, and integrating information about tumor primary location and genomics can be used to predict organ-specific metastasis risk.

Humans↗
PubMed1984

Case-control study of bladder cancer in New Jersey. I. Occupational exposures in white males.

The occupational bladder cancer risk for New Jersey white males was estimated with the use of both industry-job title-based and exposure-based analyses of data from 658 incident cases and 1,258 general population controls. The overall bladder cancer risk attributable to occupational exposures was estimated as 20-22%. A wide variety of employment categories and exposures contributed to this risk. Odds ratios were significantly high for employment as garage and gas station workers and food counter workers and/or cooks and for exposure to leather, rubber, paint, printing ink, and other organic compounds. Odds ratios for textile mill workers, chemical workers, and metal workers for the a priori high-risk employment category and odds ratios for those exposed to dyes, chlorinated compounds, and rubber showed significant differences between younger and older subjects. Bladder cancer risk associated with occupational exposures was not limited to persons with initial exposures before 25 years of age. However, there was significantly decreasing risk for bladder cancer with increasing age at first exposure for chemical workers and metal workers and for the a priori high-risk materials and metals. Drivers and/or deliverymen and miscellaneous laborers had significantly increasing bladder cancer risk with increasing duration of employment.

Adult↗