Roesler, Michelle A.

Abstract Background Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders that result in ineffective hematopoiesis. Individuals with MDS have a high risk of progressing to leukemia, with approximately 30% expected to develop acute myeloid leukemia (AML). Benzene exposure is one of the few well-established risk factors for AML, and recent studies suggest it is also a risk factor for MDS. Exposure to other occupational and residential chemicals has been inconsistently associated with hematologic malignancies. In this analysis, we evaluated occupational and residential chemical exposures as risk factors for AML and MDS using population-based data. Methods AML and MDS cases were identified by rapid case ascertainment through the Minnesota Cancer Surveillance System (MCSS). Centralized pathology and cytogenetics reviews were conducted to confirm diagnosis and classify by subtypes. Controls were identified through the Minnesota State driver's license/identification card list. Chemical exposures were measured by self-report and included occupational and residential exposure to a variety of chemicals. Unconditional logistic regression with adjustment for age, sex, previous cancer treatment, income, and farm or rural residence was used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CI). Smoking, obesity and physical activity were considered as potential confounders but did not change effect estimates by 10% or more. Results We included 265 MDS cases, 420 AML cases, and 1388 controls in this analysis. As expected, we observed significant associations between benzene and both MDS and AML (OR = 1.77, 95% CI 1.17, 2.67 and OR = 2.03, 95% CI 1.45, 2.83, respectively). Exposure to vinyl chlorides was associated with MDS (OR = 2.25, 95% CI 1.32, 3.81) but not with AML (OR = 1.36, 95% CI 0.83, 2.21). Exposure to fertilizers (OR = 1.70, 95% CI 1.11, 2.59), soot (OR = 2.64, 95% CI 1.59, 4.39), creosote (OR = 1.95, 95% CI 1.08, 3.51), inks, dyes and tanning solutions (OR = 1.63, 95% 1.02, 2.60), and coal dust (2.64, 95% CI 1.30, 5.39) were associated with AML, while no association was seen between any of these exposures and MDS (range ORs = 0.78-1.25). No significant associations were observed for occupational pesticide exposures in either group. Discussion These data confirm the importance of benzene as a risk factor for myeloid malignancy and provide risk estimates in a population-based sample. A number of other significant associations with occupational and residential chemicals were observed for AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases. Citation Format: Jenny N. Poynter, Michaela Richardson, Michelle Roesler, Cindy K. Blair, Betsy Hirsch, Phuong Nguyen, Adina Cioc, James R. Cerhan, Erica Warlick. Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3427.

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non‐Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS‐R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population‐based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.

Abstract Background: Little is known about the causes of adult leukemia. A few small studies have reported a reduced risk associated with regular use of nonsteroidal anti-inflammatory drugs (NSAID). Methods: In a population-based case–control study, we evaluated analgesic use among 670 newly diagnosed myeloid leukemia cases [including 420 acute myeloid leukemias (AML) and 186 chronic myeloid leukemias (CML)] and 701 controls aged 20 to 79 years. Prior use of aspirin, ibuprofen, acetaminophen, other NSAIDs, and COX-2 inhibitors was assessed and included frequency, duration, and quantity. ORs and 95% CIs were calculated using unconditional logistic regression adjusting for potential confounders. Results: Regular/extra strength aspirin use was inversely associated with myeloid leukemia in women (OR = 0.59, 95% CI = 0.37–0.93) but not in men (OR = 0.85, 95% CI = 0.58–1.24). In contrast, acetaminophen use was associated with an increased risk of myeloid leukemia in women only (OR = 1.60, 95% CI = 1.04–2.47). These relationships were stronger with increasing dose and duration. When stratified by leukemia type, aspirin use was inversely associated with AML and CML in women. No significant overall associations were found with ibuprofen or COX-2 inhibitors for either sex; however, a decreased risk was observed with other anti-inflammatory analgesic use for women with AML or CML (OR = 0.47, 95% CI = 0.22–0.99; OR = 0.31, 95% CI = 0.10–0.92, respectively). Conclusions: Our results provide additional support for the chemopreventive benefits of NSAIDs, at least in women. Because leukemia ranks fifth in person-years of life lost due to malignancy, further investigation is warranted. Impact: NSAIDs may reduce, whereas acetaminophen may increase, myeloid leukemia risk in women. Cancer Epidemiol Biomarkers Prev; 20(8); 1741–50. ©2011 AACR.