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1.  Disparities in the early adoption of chemo-immunotherapy for diffuse large B-cell lymphoma in the United States 
Background
Since the 1970s, CHOP chemotherapy has been the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). In 2002, randomized trials changed this standard by demonstrating that adding rituximab immunotherapy to CHOP improved survival. However, how these results influenced chemo-immunotherapy adoption in clinical practice remains unclear.
Methods
Using the National Cancer Database to compare chemo-immunotherapy use with chemotherapy alone, we collected data on demographics, stage, health insurance, area-level socio-economic status (SES), facility characteristics, and type of treatment for DLBCL patients diagnosed in the United States 2001-2004. Multivariable log binomial models examined associations between race, insurance, and treatment allocation, adjusting for covariates.
Results
Among 38,002 patients with DLBCL, 27% received chemo-immunotherapy and 50% chemotherapy alone. Patients who had localized disease, were diagnosed in 2001, black, uninsured/Medicaid insured, or lower SES were less likely to receive any form of chemotherapy (all p<0.0001). Patients who were diagnosed 2001, black [relative risk (RR) 0.83, 95% Confidence Interval (CI) 0.78-0.89], >60 years (RR 0.94, 95% CI 0.90-0.98), or had localized disease (RR 0.89, 95% CI 0.86-0.92) were less likely to receive chemo-immunotherapy. Receiving treatment at high DLBCL volume teaching/research facilities was associated with the greatest likelihood of chemo-immunotherapy (RR 1.69, 95% CI 1.52-1.89).
Conclusions
Black DLBCL patients were less likely to receive chemotherapy or chemo-immunotherapy during this period.
Impact
This large national cohort study demonstrates disparities in the diffusion of chemo-immunotherapy for DLBCL. Improving DLBCL outcomes will require efforts to extend access to proven advances in therapy to all segments of the population.
doi:10.1158/1055-9965.EPI-12-0466
PMCID: PMC4155492  PMID: 22771484
Diffuse large B-cell lymphoma; Non-Hodgkin Lymphoma; Lymphoma; Healthcare Disparities; Immunotherapy; Rituximab; Chemo-immunotherapy
2.  Changes in smoking prevalence among U.S. adults by state and region: Estimates from the Tobacco Use Supplement to the Current Population Survey, 1992-2007 
BMC Public Health  2011;11:512.
Background
Tobacco control policies at the state level have been a critical impetus for reduction in smoking prevalence. We examine the association between recent changes in smoking prevalence and state-specific tobacco control policies and activities in the entire U.S.
Methods
We analyzed the 1992-93, 1998-99, and 2006-07 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) by state and two indices of state tobacco control policies or activities [initial outcome index (IOI) and the strength of tobacco control (SOTC) index] measured in 1998-1999. The IOI reflects cigarette excise taxes and indoor air legislation, whereas the SOTC reflects tobacco control program resources and capacity. Pearson Correlation coefficient between the proportionate change in smoking prevalence from 1992-93 to 2006-07 and indices of tobacco control activities or programs was the main outcome measure.
Results
Smoking prevalence decreased from 1992-93 to 2006-07 in both men and women in all states except Wyoming, where no reduction was observed among men, and only a 6.9% relative reduction among women. The percentage reductions in smoking in men and women respectively were the largest in the West (average decrease of 28.5% and 33.3%) and the smallest in the Midwest (18.6% and 20.3%), although there were notable exceptions to this pattern. The decline in smoking prevalence by state was correlated with the state's IOI in both women and men (r = -0.49, p < 0.001; r = -0.31, p = 0.03; respectively) and with state's SOTC index in women(r = -0.30, p = 0.03 0), but not men (r = -0.21, p = 0.14).
Conclusion
State level policies on cigarette excise taxes and indoor air legislation correlate strongly with reductions in smoking prevalence since 1992. Strengthening and systematically implementing these policies could greatly accelerate further reductions in smoking.
doi:10.1186/1471-2458-11-512
PMCID: PMC3150264  PMID: 21714876
3.  Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies 
Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose–response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34–90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1–3, respectively (overall mean = 33.5, range 0–303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.
doi:10.1007/s00411-010-0307-z
PMCID: PMC3075914  PMID: 20602108
4.  Research Recommendations for Selected IARC-Classified Agents 
Environmental Health Perspectives  2010;118(10):1355-1362.
Objectives
There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans.
Data sources
For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent.
Data extraction
Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches.
Data synthesis
Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation.
Conclusions
Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.
doi:10.1289/ehp.0901828
PMCID: PMC2957912  PMID: 20562050
animal; carcinogen; carcinogenesis; epidemiology; human; IARC; mechanisms of carcinogenicity; occupational
5.  The global burden of cancer: priorities for prevention 
Carcinogenesis  2009;31(1):100-110.
Despite decreases in the cancer death rates in high-resource countries, such as the USA, the number of cancer cases and deaths is projected to more than double worldwide over the next 20–40 years. Cancer is now the third leading cause of death, with >12 million new cases and 7.6 million cancer deaths estimated to have occurred globally in 2007 (1). By 2030, it is projected that there will be ∼26 million new cancer cases and 17 million cancer deaths per year. The projected increase will be driven largely by growth and aging of populations and will be largest in low- and medium-resource countries. Under current trends, increased longevity in developing countries will nearly triple the number of people who survive to age 65 by 2050. This demographic shift is compounded by the entrenchment of modifiable risk factors such as smoking and obesity in many low-and medium-resource countries and by the slower decline in cancers related to chronic infections (especially stomach, liver and uterine cervix) in economically developing than in industrialized countries. This paper identifies several preventive measures that offer the most feasible approach to mitigate the anticipated global increase in cancer in countries that can least afford it. Foremost among these are the need to strengthen efforts in international tobacco control and to increase the availability of vaccines against hepatitis B and human papilloma virus in countries where they are most needed.
doi:10.1093/carcin/bgp263
PMCID: PMC2802672  PMID: 19934210
6.  Occupational Exposure to Polychlorinated Biphenyls and Risk of Breast Cancer 
Environmental Health Perspectives  2008;117(2):276-282.
Background
Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality.
Objectives
To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort.
Methods
We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers.
Results
Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72–0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics.
Conclusions
We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.
doi:10.1289/ehp.11774
PMCID: PMC2649231  PMID: 19270799
breast cancer; incidence; occupational epidemiology; polychlorinated biphenyls
7.  Prevalence of prehypertension and its relationship to risk factors for cardiovascular disease in Jamaica: Analysis from a cross-sectional survey 
Background
Recent studies have documented an increased risk of cardiovascular disease (CVD) in persons with systolic blood pressures of 120–139 mmHg and/or diastolic blood pressures of 80–89 mmHg, classified as prehypertension in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. In this paper we estimate the prevalence of prehypertension in Jamaica and evaluate the relationship between prehypertension and other risk factors for CVD.
Methods
The study used data from participants in the Jamaica Lifestyle Survey conducted from 2000–2001. A sample of 2012 persons, 15–74 years old, completed an interviewer administered questionnaire and had anthropometric and blood pressure measurements performed by trained observers using standardized procedures. Fasting glucose and total cholesterol were measured using a capillary blood sample. Analysis yielded crude, and sex-specific prevalence estimates for prehypertension and other CVD risk factors. Odds ratios for associations of prehypertension with CVD risk factors were obtained using logistic regression.
Results
The prevalence of prehypertension among Jamaicans was 30% (95% confidence interval [CI] 27%–33%). Prehypertension was more common in males, 35% (CI 31%–39%), than females, 25% (CI 22%–28%). Almost 46% of participants were overweight; 19.7% were obese; 14.6% had hypercholesterolemia; 7.2% had diabetes mellitus and 17.8% smoked cigarettes. With the exception of cigarette smoking and low physical activity, all the CVD risk factors had significantly higher prevalence in the prehypertensive and hypertensive groups (p for trend < 0.001) compared to the normotensive group. Odds of obesity, overweight, high cholesterol and increased waist circumference were significantly higher among younger prehypertensive participants (15–44 years-old) when compared to normotensive young participants, but not among those 45–74 years-old. Among men, being prehypertensive increased the odds of having >/=3 CVD risk factors versus no risk factors almost three-fold (odds ratio [OR] 2.8 [CI 1.1–7.2]) while among women the odds of >/=3 CVD risk factors was increased two-fold (OR 2.0 [CI 1.3–3.8])
Conclusion
Prehypertension occurs in 30% of Jamaicans and is associated with increased prevalence of other CVD risk factors. Health-care providers should recognize the increased CVD risk of prehypertension and should seek to identify and treat modifiable risk factors in these persons.
doi:10.1186/1471-2261-8-20
PMCID: PMC2551581  PMID: 18752689
8.  Mortality and Exposure Response among 14,458 Electrical Capacitor Manufacturing Workers Exposed to Polychlorinated Biphenyls (PCBs) 
Environmental Health Perspectives  2006;114(10):1508-1514.
Background
We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939–1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies.
Methods
We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling.
Results
Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55–1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98–2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02–1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72–1.45), increased with cumulative exposure (trend p-value = 0.0001).
Conclusions
This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure–response relationship for prostate cancer mortality.
doi:10.1289/ehp.9175
PMCID: PMC1626402  PMID: 17035134
cancer; electrical capacitor manufacturing; liver cancer; mortality; occupational exposure; PCBs; polychlorinated biphenyls; prostate cancer
9.  U.S. congressional district cancer death rates 
Background
Geographic patterns of cancer death rates in the U.S. have customarily been presented by county or aggregated into state economic or health service areas. Herein, we present the geographic patterns of cancer death rates in the U.S. by congressional district. Many congressional districts do not follow state or county boundaries. However, counties are the smallest geographical units for which death rates are available. Thus, a method based on the hierarchical relationship of census geographic units was developed to estimate age-adjusted death rates for congressional districts using data obtained at county level. These rates may be useful in communicating to legislators and policy makers about the cancer burden and potential impact of cancer control in their jurisdictions.
Results
Mortality data were obtained from the National Center for Health Statistics (NCHS) for 1990–2001 for 50 states, the District of Columbia, and all counties. We computed annual average age-adjusted death rates for all cancer sites combined, the four major cancers (lung and bronchus, prostate, female breast, and colorectal cancer) and cervical cancer. Cancer death rates varied widely across congressional districts for all cancer sites combined, for the four major cancers, and for cervical cancer. When examined at the national level, broad patterns of mortality by sex, race and region were generally similar with those previously observed based on county and state economic area.
Conclusion
We developed a method to generate cancer death rates by congressional district using county-level mortality data. Characterizing the cancer burden by congressional district may be useful in promoting cancer control and prevention programs, and persuading legislators to enact new cancer control programs and/or strengthening existing ones. The method can be applied to state legislative districts and other analyses that involve data aggregation from different geographic units.
doi:10.1186/1476-072X-5-28
PMCID: PMC1538995  PMID: 16796732
10.  Gliomas and Farm Pesticide Exposure in Women: The Upper Midwest Health Study 
Environmental Health Perspectives  2005;113(5):546-551.
An excess incidence of brain cancer in male farmers has been noted in several studies, but few studies have focused on women. The National Institute for Occupational Safety and Health Upper Midwest Health Study evaluated effects of rural exposures for 341 female glioma cases and 528 controls, all adult (18–80 years of age) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. On average, controls lived longer on farms than did cases. After adjusting for age, age group, education, and farm residence, no association with glioma was observed for exposure to arsenicals, benzoic acids, carbamates, chloroacetanilides, dinitroanilines, inorganics, organochlorines, organophosphates, phenoxys, triazines, or urea-based or estrogenic pesticides. An increased risk of glioma was observed for carbamate herbicides but was not statistically significant (odds ratio = 3.0; 95% confidence interval, 0.9–9.5). No association was observed between glioma and exposure to 12 widely used specific pesticides, after adjustment for age, age group, education, and any other pesticide exposure. These results were not affected after exclusion of proxy respondents (43% of cases, 2% of controls). Women were less likely than men to have applied pesticides, but more likely to have laundered pesticide-contaminated clothes. Storing pesticides in the house was associated with a statistically non-significant increased risk. Results show that exposure to pesticides was not associated with an increased risk of intracranial gliomas in women. Other farm-related factors could be etiologic factors and will be discussed in future reports.
doi:10.1289/ehp.7456
PMCID: PMC1257545  PMID: 15866761
brain cancer; case—control; farmers; glioma; Midwest; pesticides; women
11.  Priorities for development of research methods in occupational cancer. 
Occupational cancer research methods was identified in 1996 as 1 of 21 priority research areas in the National Occupational Research Agenda (NORA). To implement NORA, teams of experts from various sectors were formed and given the charge to further define research needs and develop strategies to enhance or augment research in each priority area. This article is a product of that process. Focus on occupational cancer research methods is important both because occupational factors play a significant role in a number of cancers, resulting in significant morbidity and mortality, and also because occupational cohorts (because of higher exposure levels) often provide unique opportunities to evaluate health effects of environmental toxicants and understand the carcinogenic process in humans. Despite an explosion of new methods for cancer research in general, these have not been widely applied to occupational cancer research. In this article we identify needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary prevention. Progress in occupational cancer will require interdisciplinary research involving epidemiologists, industrial hygienists, toxicologists, and molecular biologists.
PMCID: PMC1241299  PMID: 12524210

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