Blair, Cindy K.

Abstract Introduction: Tribal Nations across the Southwest have striking disparities in cancer incidence and mortality. Compounded by disproportionately low rates of cancer screening and limited access to healthcare, Native Americans are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. At the University of New Mexico Comprehensive Cancer Center, the Participant Engagement Cancer Genomic Sequencing (PE-CGS) Center is developing culturally appropriate materials and strategies to enhance the engagement and recruitment of Native Americans into genomic research. This effort aims to determine participant knowledges, attitudes, cultural beliefs, and communication preferences regarding clinical genomics testing. Ultimately, targeting improvement of cancer outcomes in Southwestern Tribal communities. Cultural adaptations are crucial with regards to biospecimen collection, storage, and usage, due to historical mistrust of research among Native communities. (i.e., Havasupai Tribe v. the Arizona Board of Regents). A Tribal Advisory Committee, consisting of Tribal leaders, Native physicians, and patient advocates oversee all aspects of the research study. The goal is to identify appropriate optimized health literacy strategies for engaging Native peoples in cancer genomic research. Methods: The team conducted semi-structured discussions with participants to understand their perspectives on motivations to join, cultural safety components, and effectiveness of engagement strategies. With participant consent, the discussions were recorded and transcribed. Analysis included the transcripts and notes taken by the interviewer and followed Grounded Theory principles. All transcripts and notes followed line-by-line analysis by three of the authors (JS, JR and TG) who met regularly to identify and discuss emergent themes. Results: As of May 31, 2024, the PE-CGS study has enrolled 112 participants and completed 39 discussions. Participants emphasized altruistic motives tied to family and community, echoing traditional values, in their decision to participate in the study. This notion emerged during interactions with Native team members, where comfort stemmed from shared experiences (healthcare system, barriers), use of Native language, and adherence to Native social norms. Additional considerations included present autonomy throughout various stages of the study (sample use, data sharing, discussions). Return of genetic testing results improved understanding of treatment options, hereditary risk, and health literacy. Conclusion: Feedback highlights the importance of aligning cultural beliefs with Western medicine through a strengths-based approach. The findings will inform improvements in respectful engagement, communication, information exchange, and recruitment processes with Native American cancer patients and cancer survivors to genomic testing studies. Citation Format: Jessica Sanchez, Koby Blackwater, Joseph Rodman, Tamar Ginossar, Andrew Sussman, Shiraz Mishra, Cindy Blair, Mallery Quetawki, Debra MacKenzie, V. Shane Pankratz, Ursa Brown-Glaberman, Jeffery Trent, Cheryl Willman. Journey to understanding indigenous peoples engagement in cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A084.

Abstract Introduction: The Patient Engagement-Cancer Genome Sequencing Research Center (PE-CGS; NCI U2C CA252973) based at the University of New Mexico Comprehensive Cancer Center (UNMCCC) with partners at Mayo Clinic Comprehensive Cancer Center, the Translational Genomics Research Institute, and the Black Hills for American Indian Health Research Center are developing culturally appropriate strategies and methods to address the underrepresentation of American Indians (AIs) in genomic research. Our efforts are directed towards the implementation of tailored cancer prevention, diagnosis, and treatment strategies that reduce cancer health disparities in Tribal communities. Methods: The PE-CGS Center has three units, each tasked with specific research components to engage AI participants in participatory, clinically-meaningful genomic research: 1) the Participant Engagement Unit; 2) the Genomics Characterization Unit; and 3) the Engagement Optimization Unit (EOU). The Center also has a Tribal Advisory Committee, composed of Tribal Governors, Presidents, and tribal health advocates and experts, who provide direction on all research matters. The PE-CGS EOU uses iterative rapid-cycle research techniques to optimize engagement and shares these strategies with other units for timely implementation. To date, the EOU has developed and implemented three key efforts. First, to aid in recruiting participants for the study, the EOU tailored a series (6) of participant-facing informational materials that include artwork from a local AI artist who combined her traditional and scientific knowledge to prepare complementary imagery. Second, the EOU is currently implementing a series of semi-structured discussions to document participant perceptions on criteria including engagement, communication, and education. Lastly, the EOU implemented a survey among UNMCCC providers on their return of results processes. Results: EOU discussions are ongoing and have provided important perspectives on participant satisfaction and areas for improvement. Participants have commended study staff on their efforts to make enrollment straightforward. Participants report discussing the study with family prior to enrolling, highlighting the importance of continuing to engage with the entire community on the goals of the study. The provider return of results survey is complete (n=42/62, response rate=68%); one key finding was that providers who return somatic test results rarely provide participants with a hard copy of the results or utilize complementary materials that might enhance their explanation of the test findings. Conclusion: The EOU serves an innovative function through its rapid-cycle methods to optimize participant engagement. Although participants are generally pleased with their study participation, there are numerous opportunities for improvement. The informational materials represent a novel contribution to the field of genomic research. Efforts will continue to implement optimized processes for effective engagement of AI communities in genomic research and cancer care delivery. Citation Format: Shoshana Adler Jaffe, Kendal Jacobson, Joseph Rodman, Cindy Blair, Debra MacKenzie, Mallery Quetawki, Tamar Ginossar, V. Shane Pankratz, Andrew Sussman, Ursa Brown-Glabermen, Jeffrey Trent, Cheryl Willman, Shiraz I. Mishra. The art of science: Painting a new image of genomic research in the indigenous communities of the Southwest [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B134.

Abstract Background: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research. Methods: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities. Results: Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants. Conclusions: PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries. Impact: Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement.

Abstract Overweight [body mass index (BMI) 25.0-29.9 kg/m2] and obesity (BMI ≥30 kg/m2) are risk factors for several malignancies. The Iowa Women's Health Study was examined to determine whether increased BMI was associated with leukemia development. Over 40,000 Iowa women (ages 55-69 years) completed a self-administered lifestyle and health questionnaire in 1986 that included current height and weight. Two hundred women developed leukemia during the period 1986 to 2001 including 74 acute myelogenous leukemia (AML) and 88 chronic lymphocytic leukemia. The risk of AML was increased among women who reported being overweight or obese (relative risk, 1.9; 95% confidence interval, 1.0-3.4; relative risk, 2.4; 95% confidence interval, 1.3-4.5; Ptrend = 0.006) compared with women of normal weight. There was little evidence of a positive association for chronic lymphocytic leukemia (Ptrend = 0.6). Given the prevalence of overweight and obesity in the United States, the population attributable risk of AML due to obesity could approach 30%.

Abstract Recent studies have reported an increased risk of breast, endometrial, ovarian, and gall bladder cancer associated with ERT. One proposed mechanism by which ERT increases risk is through the binding of estrogen to receptors at the tissue site. Estrogen receptors are also present on certain hematopoietic cells as well as on myeloid leukemia cells. Further, downregulation of the estrogen receptor through DNA methylation has been associated with increased acute myeloid leukemia (AML) survival. We evaluated whether ERT is associated with an increased risk of leukemia, particularly AML, in the Iowa Women’s Health Study. A cohort of 37,172 post-menopausal Iowa women ages 55 to 69 years with no history of prior cancer was linked annually to the population-based state cancer registry through 2001. In addition to other self-reported cancer risk factors, participants were asked about current and former use of ERT in 1986 and on four subsequent follow-up questionnaires. A total of 201 cases of leukemia were identified over 16 years of follow-up including 64 AMLs and 87 chronic lymphocytic leukemias (CLLs). Compared to never users of ERT at study baseline, current [multivariate relative risk (RR), 1.09; 95% Confidence Interval (CI) 0.70–1.72) and former users (RR=0.81, 95% CI=0.58–1.14) were at no increased risk of developing leukemia. For AML, current users also had no increased risk (RR=0.86, 95% CI=0.39–1.92) and there was a suggestion that former users had a slight decreased risk (RR=0.68, 95% CI=0.38–1.22). For CLL, all results were around unity. Duration of ERT or time-dependent use had no appreciable effect on the RRs. We conclude that ERT use is unlikely to be a risk factor for leukemia, including AML. Supported by NCI R01 CA39741.

Abstract Abstract 873 Each year in the United States, approximately 45,000 individuals are newly diagnosed with leukemia and 22,000 will die of the disease. Due to this poor survival, leukemia ranks fifth in person years of life lost among specific cancers. Little is known about causes, although exposure to solvents, radiation, pesticides and, to a modest extent, cigarette smoke has been implicated for some subtypes. The last comprehensive report of leukemia trends covered the period 1973–1998 [Xie Y et al, Cancer 2003]. Evaluation of recent leukemia incidence trends could provide important new etiologic insights. Using Surveillance, Epidemiology and End Results (SEER) Program data, we analyzed leukemia incidence trends in U.S. adults (≥ 20 years of age) by age, leukemia subtype (acute myeloid (AML), acute lymphoid (ALL), chronic myeloid (CML), chronic lymphoid (CLL)) sex, race, and ethnicity for the period 1987–2007. Frequencies, age-adjusted incidence rates (IR, per million), and trends were calculated along with annual percent change (APC) and corresponding 95% confidence intervals (CI). Joinpoint analyses were used to detect any significant directional changes in IRs over the period. Of 43,970 newly diagnosed cases identified, IRs increased with age and were consistently higher in males than females for all four subtypes. The highest IRs occurred for CLL (54.4), followed by AML (38.3), CML (20.6) and ALL (7.0). With regard to trends, IRs for CLL (APC -0.5; CI: -0.9, -0.1) and CML (APC -1.2; CI: -1.6, -0.8) declined over the time period; declines were observed in males and females, and by race and ethnicity. Male(M):Female(F) IR ratios remained relatively constant at approximately 2.0 and 1.7, respectively. For ALL, IRs decreased in males (APC -0.9; CI: -1.9, 0.2) but slightly increased in females (APC 0.4; CI: -1.0, 1.7), which was most notable in Hispanics (APC 4.0; CI: 1.2, 6.8). In contrast to CML and CLL, the overall M:F rate ratio for ALL decreased, although it did not reach statistical significance (p=0.08). For AML, IRs increased significantly for males (APC 1.0; CI: 0.3,1.6) and females (APC 1.7; CI: 0.7, 2.7) from 1987–2000 and 1987–2001, respectively. However, since then, AML IRs for males have been significantly decreasing by 4.2% per year (CI: -6.4, -2.1), while IRs for females have been decreasing by 1.6% per year (CI: -4.1, 0.9). Across the entire time period 1987–2007, there was a statistically significant negative trend (p=0.002) in the M:F IR ratio for AML. Decreasing IRs across many leukemias since 1987 are unlikely to reflect changes in screening or diagnostic coding practices. Instead, these observations may reflect temporal changes in etiologically relevant environmental exposures. Of note, the prevalence of cigarette smoking in the population has decreased and occupational safety practices (e.g., reducing solvent/radiation/pesticide exposure) have improved over the last several decades, which could contribute to the gradual decreases in some IRs observed. In contrast, the rapid and significant decrease noted for AML since 2000, especially following a significant increase, was striking and deserved additional scrutiny. We further consulted with our cancer registry colleagues to determine whether the introduction of myelodysplastic syndrome (MDS) as a new malignancy in SEER in 2001 could be influencing recent AML trends given the (apparently) coincidental overlap in time periods. Of note, approximately one third of MDS patients subsequently develop AML. We learned that AML following an MDS diagnosis from 2001–2009 was not reportable to SEER and therefore not counted. We are not aware that this has been documented in the literature. However, beginning for 2010 diagnoses, SEER changed this practice such that AML following MDS will be captured as a second malignancy. Based on these changes in AML surveillance, it will especially be important to monitor future trends for this malignancy. Overall, this study demonstrates the value of in-depth analyses of SEER cancer IRs and trends; analyses may reveal patterns of clinical and/or etiological importance, or, in the instance of AML, unpublished coding rule changes. Disclosures: No relevant conflicts of interest to declare.

Benzene exposure is one of the few well‐established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) using population‐based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self‐report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR = 1.77, 95% CI 1.19, 2.63 and OR = 2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR = 2.05, 95% CI 1.15, 3.63 and OR = 2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions and coal dust were associated with AML (range ORs = 2.68–4.03), while no association was seen between these exposures and MDS (range ORs = 0.57–1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population‐based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with 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.

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.

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.