Anneclaire J. De Roos

Background: Residence near municipal solid waste incinerators, a major historical source of dioxin emissions, has been associated with increased risk of non-Hodgkin lymphoma (NHL) in European studies. The aim of our study was to evaluate residence near industrial combustion facilities and estimates of dioxin emissions in relation to NHL risk in the United States. Methods: We conducted a population-based case–control study of NHL (1998–2000) in four National Cancer Institute-Surveillance Epidemiology and End Results centers (Detroit, Iowa, Los Angeles, Seattle). Residential histories 15 years before diagnosis (similar date for controls) were linked to an Environmental Protection Agency database of dioxin-emitting facilities for 969 cases and 749 controls. We evaluated proximity (3 and 5 km) to 10 facility types that accounted for >85% of U.S. emissions and a distance-weighted average emission index (AEI [ng toxic equivalency quotient (TEQ)/year]). Results: Proximity to any dioxin-emitting facility was not associated with NHL risk (3 km OR = 1.0, 95% CI 0.8-1.3). Risk was elevated for residence near cement kilns (5 km OR = 1.7, 95% CI 0.8-3.3; 3 km OR = 3.8, 95% CI 1.1-14.0) and reduced for residence near municipal solid waste incinerators (5 km OR = 0.5, 95% CI 0.3-0.9; 3 km OR = 0.3, 95% CI 0.1-1.4). The AEI was not associated with risk of NHL overall. Risk for marginal zone lymphoma was increased for the highest versus lowest quartile (5 km OR = 2.6, 95% CI 1.0-6.8; 3 km OR = 3.0, 95% CI 1.1-8.3). Conclusions: Overall, we found no association with residential exposure to dioxins and NHL risk. However, findings for high emissions and marginal zone lymphoma and for specific facility types and all NHL provide some evidence of an association and deserve future study.

B-cell activation biomarkers have been associated with increased risk of non-Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar association may exist in general populations has not been established. We conducted a case-control study within the Women's Health Initiative Observational Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30, sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL diagnosis in 491 cases and 491 controls. Using logistic regression to estimate odds ratios, we observed strong associations between NHL and markers for all B-cell NHL and for major subtypes. Women with marker levels in the highest-versus-lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5-fold increased risk of B-NHL. In addition, there were significant trends of risk with increasing levels of these markers present. Associations were strongest for cases with shortest lag times between blood draw and diagnosis (Cancer Res; 72(18); 4733–43. ©2012 AACR.

We investigated cross-sectional associations of body composition and weight change with polychlorinated biphenyls (PCB) and organochlorine pesticides/pesticide metabolites measured in blood collected at the baseline of the Physical Activity for Total Health study of postmenopausal, overweight women living in the Seattle, Washington metropolitan area. Indicators of greater adiposity were associated with lower plasma concentrations of most PCBs with six or more chlorine atoms. This pattern was observed for current weight, body mass index, fat mass percent, subcutaneous abdominal fat, intra-abdominal fat, waist circumference, hip circumference, waist-to-hip ratio, and maximum adult weight. Conversely, PCB 105, PCB 118, and p,p′-DDE were generally increased or showed no association with these variables. Weight gain since age 35 was associated with lower concentrations of almost every organochlorine we studied, and past weight loss episodes of at least 20 pounds (≥9.1 kg) were associated with higher concentrations. Our results have implications for epidemiologic studies of organochlorines in terms of covariates that may be important to consider in statistical analyses, particularly as such considerations may differ importantly by specific analyte. Our finding of increased organochlorine concentrations with past weight loss episodes may have public health significance; however, this association requires confirmation in longitudinal studies.

Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.

Myelodysplastic syndromes (MDS) incidence is unclear because of historical lack of population‐based registration and possibly because of underdiagnosis. We conducted a study to evaluate completeness of MDS registration in the Seattle‐Puget Sound region of the Surveillance, Epidemiology, and End Results (SEER) program—which has reported the highest rates among the SEER registries since mandatory reporting of MDS began in 2001. We identified incident MDS cases of any age that occurred within a nonprofit healthcare system in western Washington State in 2005 or 2006 through the local SEER registry or by relevant diagnostic code followed by medical chart review to classify these patients as unlikely, possible, or definite/probable MDS. We calculated age‐standardized incidence rates for all identified MDS cases and for case groups based on identification method, and we summarized medical histories of the MDS patients. MDS incidence in our study population was estimated as 7.0 per 100,000 person‐years in 2005–2006 when combining MDS cases identified by SEER and definite/probable cases identified by chart review, which was similar to the rate of 6.9 reported by our local SEER registry. The addition of possible MDS cases identified from chart review increased the rate to 10.2 per 100,000. MDS patients frequently had previous cancer diagnoses (25%) and comorbidities such as high blood pressure and diabetes. Our investigation suggests that although reporting of confirmed MDS diagnoses in our region appears complete, MDS incidence is likely underestimated because of omission of cases who are symptomatic but do not receive definitive diagnoses. Am. J. Hematol., 2010.

Objectives Incidence of myelodysplastic syndromes (MDS) has been described in the United States since its inclusion in the Surveillance, Epidemiology, and End Results program in 2001, and the Seattle-Puget Sound region of Washington State has among the highest rates of the registries. In this investigation, we described small-scale incidence patterns of MDS within the Seattle-Puget Sound region from 2002 to 2006 and identified potential spatial clusters to inform planning of future studies of MDS etiology. Methods We used a spatial disease mapping model to estimate smoothed relative risks for each census tract and to describe the spatial component of variability in the incidence rates. We also used two methods to describe the location of potential MDS clusters: the approach of Besag and Newell and the Kulldorff spatial scan statistic. Results Our findings from all three approaches indicated the most likely areas of increased MDS incidence were located on Whidbey Island in Island County. Conclusion Interpretation is limited because our data are based on the residential location of the MDS case only at the time of diagnosis. Nevertheless, inclusion of identified cluster regions in future population-based research and investigation of individual-level exposures could shed light on environmental risk factors for MDS.

We hypothesized that intentional weight loss may be associated with development of lymphohematopoietic cancers, based on observations of immune suppression following weight loss in short-term studies. At the baseline of the Women’s Health Initiative Observational Study (1994–1998), participants reported information about intentional weight loss episodes in the past 20 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) among 81,219 women for associations between past intentional weight loss and risk of developing non-Hodgkin lymphoma (NHL), leukemia, and multiple myeloma during an average 9.9 years of follow-up. The risk of NHL was associated with having lost a large maximum amount of weight (≥50 pounds, HR = 1.68, 95% CI 1.13–2.50). NHL risk also varied by the frequency of intentional weight loss; women had increased risk if they lost 50 pounds or more ≥3 times (HR = 1.97, 95% CI 0.93–4.16; p trend by frequency = 0.09) or 20–49 pounds ≥3 times (HR = 1.55, 95% CI 1.00–2.40; p trend = 0.05), but there was no risk associated with smaller amounts of weight loss (10–19 pounds ≥3 times, HR = 0.78, 95% CI 0.46–1.33). These associations persisted with adjustment for body mass index at different ages. We observed non-significant associations of similar magnitude for multiple myeloma, but past intentional weight loss episodes were not associated with leukemia. Further assessment of intentional weight loss as a possible risk factor for lymphomas may provide insight into the etiology of these cancers.

Background: Traffic-related air pollution has been associated with adverse health outcomes, and the immune system may be a biologic mediator of health effects. Objectives: We analyzed associations between living near major roads and immune status as measured by five immune assays. We hypothesized that living near a freeway, arterial, or truck route would be associated with increased inflammation and decreased immune function. Methods: We used a geographic information system (GIS) to determine residential proximity to major roads among 115 postmenopausal, overweight women in the greater Seattle, Washington (USA), area whose immunity was assessed at the baseline visit of an exercise intervention trial. We evaluated three inflammatory markers (C-reactive protein, serum amyloid A, and interleukin-6) and two functional assays of cellular immunity [natural killer (NK) cell cytotoxicity and T-lymphocyte proliferation]. Results: Women living within 150 m of arterial roads had 21% lower NK cytotoxicity compared with women who lived farther from an arterial [mean cytotoxicity, 19.5%; 95% confidence interval (CI), 15.6–23.5%; vs. mean cytotoxicity, 24.8%; 95% CI, 22.0–27.5%], after adjustment for both individual-level and census tract–level demographic characteristics. This association was limited to women who reported exercising near traffic. Fewer women lived near freeways and truck routes. Markers of inflammation and lymphocyte proliferation did not consistently differ according to proximity to major roads. Conclusions: If the observed association between residential proximity to traffic and decreased NK cytotoxicity is confirmed in other populations, our results may have implications for local land use policy.

Myelodysplastic syndromes (MDS) following treatment with chemotherapy or irradiation are termed 'secondary' MDS. Clinical observations suggest a worse prognosis for secondary than for primary MDS, but differences in survival have not been studied in a general population sample. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) program to describe survival in MDS patients according to previous cancer diagnosis. Our study included 3,938 MDS cases diagnosed in 2001-2004 and reported by registries which have participated in SEER since the 1970s. A previous cancer diagnosis (26% of MDS cases) was associated with 13% increased risk of death from any cause among MDS cases (hazard ratio [HR]=1.13, 95% confidence interval [CI]: 1.02-1.25). Radiation treatment for a previous cancer was associated with 52% increased risk of death (95% CI: 1.15-2.02). Shortened survival was most pronounced if the latency between the previous cancer and MDS was less than five years, including lung cancer diagnosed in the year preceding MDS (HR = 3.43, 95% CI: 1.93-6.10) and lymphohematopoietic cancer 1-5 years before MDS (HR = 2.11; 95% CI: 1.33-3.36). Our results confirm a more severe prognosis for secondary MDS than for primary MDS, associated with certain types and treatments of previous cancer.