Ross, Julie A.

AbstractBackground: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown.Methods: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare. RR and 95% confidence intervals (CI) were estimated utilizing Cox proportional hazard regression.Results: After >250,000 person-years of follow-up, 257 cases of MPN were identified (172 ET, 64 PV). Ever use of hormone therapy (HT) was associated with an increased risk of ET (RR = 1.63; 95% CI, 1.19–2.23) but a decreased risk of PV (RR = 0.58; 95% CI, 0.34–0.98). There were no statistically significant associations of oral contraceptives or reproductive factors with MPN risk overall, or by MPN subtype. Bilateral oophorectomy was associated with increased risk of ET (RR = 1.58; 95% CI, 1.11–2.25) and decreased risk of PV (RR = 0.32; 95% CI, 0.12–0.88). There was no association of ovulatory years with ET risk; however, there was increased risk of PV (RR = 1.68 for >36.8 compared with ≤27.6 years; P trend = 0.045). Adjustment for potential confounding factors did not alter these associations.Conclusions: HT use and bilateral oophorectomy had opposite associations for ET and PV. Except for ovulatory years and PV risk, reproductive history did not appear to play a role in the etiology of MPN.Impact: This study suggests different mechanistic impacts of estrogen, and perhaps distinct etiologies, for the two major MPN subtypes. Cancer Epidemiol Biomarkers Prev; 25(1); 151–7. ©2015 AACR.

Abstract Background: Essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) are collectively classified as myeloproliferative neoplasms (MPN). Given that little is known about their etiology, we investigated the role of anthropometric, medical and lifestyle factors in the development of MPNs and the common subtypes (ET & PV) in a population-based cohort of women. Methods: The IWHS is a prospective cohort of Iowa women aged 55-69 years at enrollment in 1986. Participants completed 6 self-administered questionnaires between 1986-2004. This analysis includes 27370 women who completed the 1993 questionnaire, had no history of cancer, and were enrolled in Medicare at least 1 year. MPN cases through 2004 were identified by linkage to Medicare. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression, with age as the underlying time variable. Results: After >250,000 person-years of follow-up, 257 cases of MPNs were identified (172 ET, 64 PV and 21 MF). Height, body mass index (BMI) and waist-to-hip ratio were not associated with risk of MPN. In subtype analysis, BMI was positively associated with risk of ET (RR=1.52 for >29.3 vs <23.5 kg/m2; p-trend=0.042) but not PV. Physical activity (PA) showed a suggestive association with MPN (RR=0.74 for high vs low activity; p-trend=0.063), specific only to ET (RR=0.66; p-trend=0.04). Diabetes (DM) was positively associated with risk of MPN (RR=1.51; 95% CI 1.02-2.24), also specific only to ET (RR=1.82; 95% CI 1.16-2.84). Regular use of aspirin, but not other non-steroidal anti-inflammatory agents, was associated with a lower risk of MPN (RR=0.71; 95% CI 0.55-0.92); slightly stronger for ET (RR=0.68; 95% CI 0.50-0.93) than for PV (RR=0.84; 95% CI 0.50-1.43). There was no dose-response with frequency of use. Cigarette smoking was associated with risk of MPN, which was stronger for PV (RR=0.94 for former and RR=2.83 for current; p-trend=0.016) than for ET (RR=1.28 for former and RR=1.32 for current; p-trend=0.15). There were no associations with alcohol use. In a multivariate model for ET, the associations for BMI (RR=1.28; p-trend=0.21) and DM (RR=1.51; 95% CI 0.92-2.46) attenuated, while there was little change for PA (RR=0.66; p-trend=0.062) or aspirin use (RR=0.70; 95% CI 0.51-0.96). In PV, there was little impact on the association with smoking (RR=0.92 for former and RR=2.67 for current; p-trend=0.028) after adjustment for BMI, PA, DM and aspirin use. Conclusions: Risk factors were unique to the 2 most common types of MPN. ET was associated with obesity-related factors (PV was not), and PV was associated with current smoking (ET was not). Aspirin use had a stronger inverse association for ET. Our results suggest distinct etiologies of these PMN subtypes, and raises mechanistic hypotheses related to inflammation for ET and smoking-related carcinogenic pathways for PV. Citation Format: Alexis D. Leal, Carrie A. Thompson, Alice Wang, Robert A. Vierkant, Thomas M. Habermann, Julie A. Ross, Beth A. Virnig, James R. Cerhan. Anthropometric, medical history and lifestyle risk factors for myeloproliferative neoplasms in the Iowa Women's Health Study (IWHS) cohort. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2536. doi:10.1158/1538-7445.AM2013-2536

Abstract Background: Allergic diseases signify immune dysregulation attributable to underlying genetics and environmental exposures. Associations between various allergies and hematopoietic cancers have been observed, albeit inconsistently; however, few prospective studies have examined the risk, and even fewer among older adults. Methods: We examined risk of incident hematopoietic cancers in those reporting allergic diseases in a population-based cohort of 22,601 older women (Iowa Women's Health Study). Self-reported allergic status, including asthma, hay fever, eczema, and/or other allergies, was determined via questionnaire in 1997 (mean age, 72 years; range, 63–81 years). Incident cancers were ascertained by linkage with the Iowa Cancer Registry from 1997 to 2011. Cox proportional hazards regression was performed to estimate multivariate-adjusted HR and 95% confidence intervals (CI) for myeloid (N = 177) and lymphoid (N = 437) malignancies, respectively. Results: Allergic diseases were not associated with risk of myeloid (HR, 1.00; 95% CI, 0.72–1.37) or lymphoid (HR, 0.99; 95% CI, 0.81–1.22) malignancies overall, or for most allergic and malignant subtypes examined. Self-reported asthma was positively associated with development of myelodysplastic syndrome (MDS; HR, 2.00; 95% CI, 0.93–4.32). In addition, there was a 30% to 40% decrease in risk of both lymphoid and myeloid cancers in those reporting rural residences but no association in those reporting urban residences; the interaction between residence and allergy was statistically significant for lymphoid malignancies (Pinteraction = 0.05). Conclusions and Impact: These results suggest that asthma may contribute to the pathogenesis of MDS, a finding consistent with the chronic antigen stimulation hypothesis. Susceptibility differences by location of residence are concordant with the hygiene hypothesis and merit additional exploration. Cancer Epidemiol Biomarkers Prev; 23(9); 1903–12. ©2014 AACR.

Key Points NK cells and their expression of FcRγIII (CD16) are decreased in MDS and inversely correlate with a substantial increase in MDSCs. CD16xCD33 BiKE potently activates blood and marrow MDS-NK cells at all diseases stages to lyse CD33+ MDS and CD33+ MDSC targets.

Classical myeloproliferative neoplasms (MPNs) are composed of essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), the etiology of which is largely unknown. We investigated the role of anthropometric, medical and lifestyle factors with risk of MPN in a prospective cohort of 27,370 women aged 55–69 years at enrollment. After >250,000 person‐years of follow‐up, 257 cases of MPN were identified (172 ET, 64 PV, 21 MF). Risk factor profiles were mostly unique for the two most common types, ET and PV. ET was associated with energy balance factors including body mass index (RR = 1.52 for >29.3vs. <23.4 kg/m2;p‐trend = 0.042), physical activity (RR = 0.66 for highvs. low;p‐trend = 0.04) and adult onset diabetes (RR = 1.82;p = 0.009), while PV was not. PV was associated with current smoking (RR = 2.83;p‐trend = 0.016), while ET was not. Regular use of aspirin was associated with lower risk of ET (RR = 0.68;p = 0.017). These results broadly held in multivariate models. Our results suggest distinct etiologies for these MPN subtypes and raise mechanistic hypotheses related to obesity‐related inflammatory pathways for ET and smoking‐related carcinogenic pathways for PV. Regular aspirin use may lower risk for ET.

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.

AbstractPrevious epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. We studied the association between allergy history and incident colorectal cancer (n = 410) prospectively in 21,292 Iowa women followed for 8 years. Allergy was defined from four self-reported questions about physician-diagnosed asthma (a), hay fever (b), eczema or allergy of the skin (c), and other allergic conditions (d). A history of any allergy was inversely associated with incident colorectal cancer: after multivariate adjustment, the hazard ratio (HR) was 0.74 [95% confidence interval (95% CI), 0.59-0.94]. Compared with women with no allergy, women reporting only one of the four types of allergy and women reporting two or more types had HRs of 0.75 (95% CI, 0.56-1.01) and 0.58 (95% CI, 0.37-0.90), respectively (P trend = 0.02). The inverse association persisted in analyses restricted to any type of nonasthmatic allergy (HR, 0.73; 95% CI, 0.56-0.95). HRs were similar for rectal and colon cancers as well as for colon subsites: proximal and distal (HRs for any allergy ranged from 0.63 to 0.78 across these end points). Allergy history, which may reflect enhanced immunosurveillance, is associated with a reduced risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2357–62)

AbstractThe etiology of acute myeloid leukemia (AML) is relatively unknown. Incidence rates are highest in the agricultural Midwest region compared with other regions of the United States. Many studies have examined the relationship between farming and leukemia, but most have mainly focused on men. We examined the potential association between farm or rural residence and AML in the Iowa Women's Health Study. In 1986, 37,693 women who were free of prior cancer completed a lifestyle and health questionnaire, which included a question on the place of residence. Women were subsequently followed until 2002 for cancer incidence; 79 women developed AML during the time period. Women who lived on a farm at baseline were more likely (relative risk, 1.91; 95% confidence interval, 1.19-3.05) to develop AML compared with women who did not live on a farm. Further, women who reported living on a farm or in a rural area were twice as likely (relative risk, 2.38; 95% confidence interval, 1.33-4.26) to develop AML compared with women who lived in a city with a population of &gt;10,000 people. These results provide evidence that women who live on farms or rural areas are at an increased risk of AML.