Agricultural Pesticide Use and Risk of t(14;18)-Defined Subtypes of Non-Hodgkin Lymphoma

Pesticides have been specifically associated with the t(14;18)(q32;q21) chromosomal translocation. To investigate whether the association between pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case subjects in a population-based case-control study conducted in Nebraska between 1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides, herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)-negative case subjects with those among 1432 control subjects. Multivariate polytomous logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with farmers who never used pesticides, the risk of t(14;18)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95%CI, 1.0-6.9), crop insecticides (OR = 3.0; 95% CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0; 95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)-negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. We conclude that insecticides, herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but not t(14;18)-negative NHL. These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research. (Blood. 2006; 108:1363-1369

The National Cancer Institute Cohort Consortium : An International Pooling Collaboration of 58 Cohorts from 20 Countries

Cohort studies have been central to the establishment of the known causes of cancer. To dissect cancer etiology in more detail-for instance, for personalized risk prediction and prevention, assessment of risks of subtypes of cancer, and assessment of small elevations in risk-there is a need for analyses of far larger cohort datasets than available in individual existing studies. To address these challenges, the NCI Cohort Consortium was founded in 2001. It brings together 58 cancer epidemiology cohorts from 20 countries to undertake large-scale pooling research. The cohorts in aggregate include over nine million study participants, with biospecimens available for about two million of these. Research in the Consortium is undertaken by >40 working groups focused on specific cancer sites, exposures, or other research areas. More than 180 publications have resulted from the Consortium, mainly on genetic and other cancer epidemiology, with high citation rates. This article describes the foundation of the Consortium; its structure, governance, and methods of working; the participating cohorts; publications; and opportunities. The Consortium welcomes newmembers with cancer-oriented cohorts of 10,000 or more participants and an interest in collaborative research. (C) 2018 AACR.Peer reviewe

Fine Particulate Air Pollution and Mortality: Response to Enstrom's Reanalysis of the American Cancer Society Cancer Prevention Study II Cohort

The first analysis of long-term exposures to air pollution and risk of mortality using the American Cancer Society Cancer Prevention Study II (ACS CPS-II) cohort was published in 1995.1 Subsequently, extensive independent reanalysis2 and multiple extended analyses3-7 were conducted. These studies have consistently demonstrated that exposure to fine particulate matter air pollution (PM2.5) is associated with increased risk of mortality, especially cardiopulmonary or cardiovascular disease mortality. A recent analysis by Enstrom, based on early data from the ACS CPS-II cohort, reports no significant relationship between PM2.5 and total mortality.8 The author asserts that the original analyses, reanalyses, and the extended analyses found positive PM2.5–mortality relationships because of selective use of CPS-II and PM2.5 data

Lung Cancer and Cardiovascular Disease Mortality Associated with Ambient Air Pollution and Cigarette Smoke: Shape of the Exposure–Response Relationships

Background: Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine particulate matter < 2.5 μm in diameter (PM2.5) from ambient air pollution. Recent research indicates that the exposure–response relationship for CVD is nonlinear, with a steep increase in risk at low exposures and flattening out at higher exposures. Comparable estimates of the exposure–response relationship for lung cancer are required for disease burden estimates and related public health policy assessments

Ambient Air Pollution and Cancer Mortality in the Cancer Prevention Study II

BACKGROUND: The International Agency for Research on Cancer classified both outdoor air pollution and airborne particulate matter as carcinogenic to humans (Group 1) for lung cancer. There may be associations with cancer at other sites; however, the epidemiological evidence is limited. OBJECTIVE: The aim of this study was to clarify whether ambient air pollution is associated with specific types of cancer other than lung cancer by examining associations of ambient air pollution with nonlung cancer death in the Cancer Prevention Study II (CPS-II). METHODS: Analysis included 623,048 CPS-II participants who were followed for 22 y (1982-2004). Modeled estimates of particulate matter with aerodynamic diameter <2.5microm (PM2.5) (1999-2004), nitrogen dioxide (NO2) (2006), and ozone (O3) (2002-2004) concentrations were linked to the participant residence at enrollment. Cox proportional hazards models were used to estimate associations per each fifth percentile-mean increment with cancer mortality at 29 anatomic sites, adjusted for individual and ecological covariates. RESULTS: We observed 43,320 nonlung cancer deaths. PM2.5 was significantly positively associated with death from cancers of the kidney {adjusted hazard ratio (HR) per 4.4 mug/m3=1.14 [95% confidence interval (CI): 1.03, 1.27]} and bladder [HR=1.13 (95% CI: 1.03, 1.23)]. NO2 was positively associated with colorectal cancer mortality [HR per 6.5 ppb=1.06 (95% CI: 1.02, 1.10). The results were similar in two-pollutant models including PM2.5 and NO2 and in three-pollutant models with O3. We observed no statistically significant positive associations with death from other types of cancer based on results from adjusted models. CONCLUSIONS: The results from this large prospective study suggest that ambient air pollution was not associated with death from most nonlung cancers, but associations with kidney, bladder, and colorectal cancer death warrant further investigation. https://doi.org/10.1289/EHP1249

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis