Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer.

American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20-49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.

Pathway-based signatures predict patient outcome, chemotherapy benefit and synthetic lethal dependencies in invasive lobular breast cancer.

BACKGROUND: Invasive Lobular Carcinoma (ILC) is a morphologically distinct breast cancer subtype that represents up to 15% of all breast cancers. Compared to Invasive Breast Carcinoma of No Special Type (IBC-NST), ILCs exhibit poorer long-term outcome and a unique pattern of metastasis. Despite these differences, the systematic discovery of robust prognostic biomarkers and therapeutically actionable molecular pathways in ILC remains limited. METHODS: Pathway-centric multivariable models using statistical machine learning were developed and tested in seven retrospective clinico-genomic cohorts (n = 996). Further external validation was performed using a new RNA-Seq clinical cohort of aggressive ILCs (n = 48). RESULTS AND CONCLUSIONS: mRNA dysregulation scores of 25 pathways were strongly prognostic in ILC (FDR-adjusted P < 0.05). Of these, three pathways including Cell-cell communication, Innate immune system and Smooth muscle contraction were also independent predictors of chemotherapy response. To aggregate these findings, a multivariable machine learning predictor called PSILC was developed and successfully validated for predicting overall and metastasis-free survival in ILC. Integration of PSILC with CRISPR-Cas9 screening data from breast cancer cell lines revealed 16 candidate therapeutic targets that were synthetic lethal with high-risk ILCs. This study provides interpretable prognostic and predictive biomarkers of ILC which could serve as the starting points for targeted drug discovery for this disease.

Guideline-concordant breast cancer care by patient race and ethnicity accounting for individual-, facility- and area-level characteristics: a SEER-Medicare study.

PURPOSE: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors. METHODS: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties. RESULTS: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: ORBlack 0.83 (0.79-0.88), ORAIAN 0.66 (0.54-0.81); known stage: ORBlack 0.87 (0.80-0.94), ORAIAN 0.63 (0.47-0.85); seeing an oncologist: ORBlack 0.75 (0.71-0.79), ORAIAN 0.60 (0.47-0.72); locoregional treatment: ORBlack 0.80 (0.76-0.84), ORAIAN 0.84 (0.68-1.02); systemic therapies: ORBlack 0.90 (0.83-0.98), ORAIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits. CONCLUSIONS: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care.

LGBTQ+ cancer: priority or lip service? A qualitative content analysis of LGBTQ+ considerations in U.S. state, jurisdiction, and tribal comprehensive cancer control plans.

The National Comprehensive Cancer Control Program, a Centers for Disease Control and Prevention funded program, supports cancer coalitions across the United States (US) in efforts to prevent and control cancer including development of comprehensive cancer control (CCC) plans. CCC plans often focus health equity within their priorities, but it is unclear to what extent lesbian, gay, bisexual, transgender, queer/questioning, plus (LGBTQ+) populations are considered in CCC plans. We qualitatively examined to what extent LGBTQ+ populations were referenced in 64 U.S. state, jurisdiction, tribes, and tribal organization CCC plans. A total of 55% of CCC plans mentioned LGBTQ+ populations, however, only one in three CCC plans mentioned any kind of LGBTQ+ inequity or LGBTQ+ specific recommendations. Even fewer plans included mention of LGBTQ+ specific resources, organizations, or citations. At the same time almost three fourths of plans conflated sex and gender throughout their CCC plans. The findings of this study highlight the lack of prioritization of LGBTQ+ populations in CCC plans broadly while highlighting exemplar plans that can serve as a roadmap to more inclusive future CCC plans. Comprehensive cancer control plans can serve as a key policy and advocacy structure to promote a focus on LGBTQ+ cancer prevention and control.

Care Patterns and Outcomes for Intrahepatic Cholangiocarcinoma by Rurality of Patient Residence in a Midwestern State.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of the liver and has the worst prognosis of any tumor arising from the liver, with a 5-year survival as low as 10%. However, whether the rurality of a patient's residence impacts care received and survival has not been well studied. We aimed to assess differences in care patterns associated with the rurality of patient's residences and their impact on survival outcomes, hypothesizing that patients in rural areas would experience lower survival. METHODS: Adult patients diagnosed with ICC between 2010 and 2020 were identified in the Iowa Cancer Registry. Chi-square tests were used to compare values categorical variables by rural/urban status. Cox proportional hazards regression was used to determine associations with cancer-specific mortality. RESULTS: Of 672 patients diagnosed with ICC during the study period, 53%, 27%, and 21% resided in metropolitan, micropolitan, and rural areas, respectively. There were no significant differences in age, sex, stage at diagnosis, the proportion receiving chemotherapy within 12 weeks of diagnosis, and undergoing surgery across all groups. Additionally, the proportion receiving definitive care at a National Cancer Institute (NCI) designated center was comparable across the three groups (37% metro vs. 43% micro vs. 35% rural). However, rural residents had the highest proportion of traveling ≥ 50 miles for definitive care (22% metro vs. 41% micro vs. 56% rural). In multivariable analysis of patients with Stage 1-3 disease, younger age, receipt of chemotherapy, surgery, and definitive care at an NCI center were independently associated with decreased mortality risk. However, rural residence was not significantly associated with survival (HR: 0.64 [95% CI: 0.38-1.06]). CONCLUSION: Similar to other complex cancer diagnoses, we found that definitive care at an NCI center was associated with decreased mortality risk for patients with ICC. Although rural residence was not independently associated with survival in this cohort, rural residents traveled significantly longer distances to access definitive care. This highlights a crucial need to improve access to specialized centers for complex cancer care.

Measuring and addressing health equity: an assessment of cancer center designation requirements.

PURPOSE: By requiring specific measures, cancer endorsements (e.g., accreditations, designations, certifications) promote high-quality cancer care. While 'quality' is the defining feature, less is known about how these endorsements consider equity. Given the inequities in access to high-quality cancer care, we assessed the extent to which equity structures, processes, and outcomes were required for cancer center endorsements. METHODS: We performed a content analysis of medical oncology, radiation oncology, surgical oncology, and research hospital endorsements from the American Society of Clinical Oncology (ASCO), American Society of Radiation Oncology (ASTRO), American College of Surgeons Commission on Cancer (CoC), and the National Cancer Institute (NCI), respectively. We analyzed requirements for equity-focused content and compared how each endorsing body included equity as a requirement along three axes: structures, processes, and outcomes. RESULTS: ASCO guidelines centered on processes assessing financial, health literacy, and psychosocial barriers to care. ASTRO guidelines related to language needs and processes to address financial barriers. CoC equity-related guidelines focused on processes addressing financial and psychosocial concerns of survivors, and hospital-identified barriers to care. NCI guidelines considered equity related to cancer disparities research, inclusion of diverse groups in outreach and clinical trials, and diversification of investigators. None of the guidelines explicitly required measures of equitable care delivery or outcomes beyond clinical trial enrollment. CONCLUSION: Overall, equity requirements were limited. Leveraging the influence and infrastructure of cancer quality endorsements could enhance progress toward achieving cancer care equity. We recommend that endorsing organizations 1) require cancer centers to implement processes for measuring and tracking health equity outcomes and 2) engage diverse community stakeholders to develop strategies for addressing discrimination.

Effect of rurality and travel distance on contralateral prophylactic mastectomy for unilateral breast cancer.

PURPOSE: Despite lack of survival benefit, demand for contralateral prophylactic mastectomy (CPM) to treat unilateral breast cancer remains high. High uptake of CPM has been demonstrated in Midwestern rural women. Greater travel distance for surgical treatment is associated with CPM. Our objective was to examine the relationship between rurality and travel distance to surgery with CPM. METHODS: Women diagnosed with stages I-III unilateral breast cancer between 2007 and 2017 were identified using the National Cancer Database. Logistic regression was used to model likelihood of CPM based on rurality, proximity to metropolitan centers, and travel distance. A multinomial logistic regression model compared factors associated with CPM with reconstruction versus other surgical options. RESULTS: Both rurality (OR 1.10, 95% CI 1.06-1.15 for non-metro/rural vs. metro) and travel distance (OR 1.37, 95% CI 1.33-1.41 for those who traveled 50 + miles vs. < 30 miles) were independently associated with CPM. For women who traveled 30 + miles, odds of receiving CPM were highest for non-metro/rural women (OR 1.33 for 30-49 miles, OR 1.57 for 50 + miles; reference: metro women traveling < 30 miles). Non-metro/rural women who received reconstruction were more likely to undergo CPM regardless of travel distance (ORs 1.11-1.21). Both metro and metro-adjacent women who received reconstruction were more likely to undergo CPM only if they traveled 30 + miles (ORs 1.24-1.30). CONCLUSION: The impact of travel distance on likelihood of CPM varies by patient rurality and receipt of reconstruction. Further research is needed to understand how patient residence, travel burden, and geographic access to comprehensive cancer care services, including reconstruction, influence patient decisions regarding surgery.

Identifying research practices toward achieving health equity principles within the Cancer Prevention and Control Research Network.

PURPOSE: Although there is national recognition for health equity-oriented research, there is limited guidance for researchers to engage partnerships that promote health equity in cancer research. The Cancer Prevention and Control Research Network's (CPCRN) Health Equity Work Group developed a toolkit to guide researchers in equitable collaborations. METHODS: The CPCRN's Health Equity Work Group collectively outlined health and racial equity principles guiding research collaborations with partners that include communities, community-based organizations, implementing partners in the clinical setting including providers and health care organizations, and policy makers. Using a network-wide survey to crowdsource information around ongoing practices, we leveraged and integrated the network's experience and collaborations. RESULTS: Data from the survey formed the preliminary basis for the toolkit, with a focus on sharing fiscal resources with partners, training and capacity building, collaborative decision-making, community-driven research agenda setting, and sustainability. The final toolkit provides reflection considerations for researchers and collated exemplary resources, supported by the contemporary research. CONCLUSIONS: The toolkit provides a guide to researchers at all experience levels wanting to engage in equitable research collaborations. Future efforts are underway to evaluate whether and how researchers within and outside CPCRN are able to incorporate these principles in research collaborations.

Comparing COVID-19 Response Behaviors between a Cancer Patient Sample and a Population-Based Cancer-Free Sample in a Rural Midwestern State.

INTRODUCTION: The COVID-19 pandemic caused an increase in fear, anxiety, and depressive symptoms globally. For populations at increased risk for adverse outcomes due to illness, such as cancer patients, these worries may have been exacerbated. Understanding how the pandemic impacted cancer patients will inform better preparation for future events that cause disturbances to cancer care delivery. METHODS: This study analyzed data from two surveys to determine whether cancer patients' responses differed from a cancer-free population-based sample in terms of concerns, preventive behaviors, and thoughts on their healthcare provider's communication regarding COVID-19 in a US Midwestern state. In August 2020, a survey was sent to 10,009 Iowans aged 18 and older, randomly selected from the 2018 Iowa voter registration file. In September 2020, a survey was emailed to 2,954 cancer patients aged 18 and older who opted into the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden program. Previously validated and pretested Likert-type and multiple-choice items assessed concern regarding COVID-19, social distancing perception and behaviors, and demographic characteristics of respondents. We used χ2 tests and logistic regression to examine differences between the cancer patient and general population survey responses. RESULTS: We included 3,622 responses from the general population survey and 780 responses from the cancer patient survey in this analysis. Cancer patient survey respondents were more frequently older, lived in urban areas, had Medicare insurance coverage, had a college degree or higher, and were married. Cancer patients were more likely to report engaging in social distancing behaviors and greater concern regarding the pandemic. CONCLUSION: This study suggests differences in the impact of the COVID-19 pandemic on cancer patients compared to cancer-free members of the general population. These results indicate the need for consideration of cancer patients' physical and mental health during large-scale disruptions to cancer care.

Definitive study shows no association between ARID1A mutation status and clinical outcome in endometriosis-related ovarian cancers‡.

The ARID1A tumour suppressor protein is a component of the SWI/SNF chromatin remodelling complex, which is mutated in approximately 20% of all human cancers. ARID1A mutational status is considered to hold prognostic significance in a range of solid malignancies, yet in endometriosis-related ovarian carcinomas there has been a lack of clarity of its prognostic role. Moreover, the relationship between ARID1A status and immune infiltrate is also poorly understood. In a recent issue of The Journal of Pathology, a large comprehensive study by Heinze, Nazeran et al addressed these areas by reviewing 1,623 endometriosis-associated ovarian carcinomas and correlating ARID1A status using standardised immunohistochemistry to infer mutation status, with comprehensive clinicopathological features, mismatch repair status and CD8+ tumour infiltrating lymphocytes. The study definitively showed that ARID1A status does not provide any independent prognostic value in endometriosis-associated ovarian carcinomas. ARID1A loss was, however, shown to be associated with mismatch repair deficiency and increased CD8+ tumour infiltrating lymphocytes in endometrioid ovarian carcinoma, which may be relevant for future studies. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

M379A Mutant Tyrosine Phenol-lyase from Citrobacter freundii Has Altered Conformational Dynamics.

The M379A mutant of Citrobacter freundii tyrosine phenol-lyase (TPL) has been prepared. M379A TPL is a robust catalyst to prepare a number of tyrosines substituted at the 3-position with bulky groups that cannot be made with wild type TPL. The three dimensional structures of M379A TPL complexed with L-methionine and 3-bromo-DL-phenylalanine have been determined by X-ray crystallography. Methionine is bound as a quinonoid complex in a closed active site in 3 of 4 chains of homotetrameric M379A TPL. M379A TPL reacts with L-methionine about 8-fold slower than wild type TPL. The temperature dependence shows that the slower reaction is due to less positive activation entropy. The structure of the M379A TPL complex of 3-bromo-DL-phenylalanine has a quinonoid complex in two subunits, with an open active site conformation. The effects of the M379A mutation on TPL suggest that the mutant enzyme has altered the conformational dynamics of the active site.

Needs assessment of cancer survivors in Alaska.

PURPOSE: Little is known about cancer survivors' needs in Alaska. To address this knowledge gap, the Alaska Cancer Partnership conducted a needs assessment survey; our objectives were to identify unmet needs of Alaska's cancer survivors; identify survivor sub-populations that might benefit from targeted interventions or programming; and develop recommendations for public health and community organizations and healthcare providers for addressing cancer survivors' unmet needs. METHODS: Cancer survivors were identified using data from the Alaska Cancer Registry. A random sample of 2,600 individuals was selected to receive the survey, which assessed unmet needs across the following domains: information needs and medical care issues; quality of life; emotional and relationship issues related to cancer diagnoses; and support services. We calculated descriptive statistics for survey responses and assessed demographic predictors of unmet needs using Poisson regression. RESULTS: We received 335 survey responses, for a response of 13.7%. Only 29.9% of cancer survivors expressed that all their needs were met. The most highly ranked unmet needs were as follows: help to reduce stress in life; to know doctors were coordinating care; and managing concerns about cancer coming back. After adjustment, men, adults younger than 65 at diagnosis, Alaska Native people, survivors still receiving or who had recently received care, and people who had to travel 50+ miles for most of their care had significantly greater unmet needs than their comparison groups. CONCLUSION: This assessment provided some of the first information regarding the needs of Alaska's cancer survivors. These results will be used by Alaska Cancer Partnership members across the state to inform healthcare delivery, programs, and public health messaging to support survivors.

Smoking Patterns Among Urban Alaska Native and American Indian Adults: The Alaska EARTH 10-Year Follow-up Study.

INTRODUCTION: Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use. AIMS AND METHODS: EARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up. RESULTS: Current smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking <10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men. CONCLUSIONS: Our project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people. IMPLICATIONS: This study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people.

Ten-year weight gain is not associated with multiple cardiometabolic measures in Alaska EARTH study participants.

BACKGROUND AND AIMS: Alaska Native (AN) traditional lifestyle may be protective against chronic disease risk. Weight gain in adulthood has been linked to increases in chronic disease risk among other populations; yet, its impact among Alaska Native people has never been evaluated. We aimed to evaluate changes in obesity-related metrics over time, and determine associations of changes with cardiometabolic markers of chronic disease risk among AN people. METHODS AND RESULTS: Study participants enrolled in the southcentral Alaska Education and Research Towards Health Study in 2004-2006 were invited to participate in a follow-up study conducted 2015-2017. Of the original 1320 participants, 388 completed follow-up health assessments consisting of multiple health surveys, anthropometric measurements, and cardiometabolic measures including blood sugars, blood lipids, and blood pressure. Differences in measurements between visits were determined and associations of weight change with cardiometabolic measures evaluated. Body mass index increased by 3.7 kg/m2 among men and 4.8 kg/m2 among women. Hip circumference (1.1 cm, p < 0.01) and waist circumference (0.7 cm, p < 0.01) increased among women; only waist circumference increased among men (1.6 cm, p < 0.01). Among men, there were no associations of weight change with cardiometabolic measures. Among women, there was an inverse association between weight gain and high-density lipoprotein cholesterol only (0.17 mg/dL (CI: -3.1, -0.03), p = 0.02). CONCLUSIONS: While weight increase over a 10-year period was not associated with substantive changes in cardiometabolic measures among AN men, there was a decrease in high density lipid cholesterol associated with weight gain among AN women.

Pediatric Cancers among Alaska Native People.

OBJECTIVE: To evaluate the descriptive epidemiology of pediatric cancers among Alaska Native people. STUDY DESIGN: We used data from the Alaska Native Tumor Registry, a population-based registry capturing cancer information among Alaska Native people 1969-present. Specifically, we examined all cases of cancer diagnosed among individuals ages 0-19 years. Cases were classified according to the International Classification of Childhood Cancers, 3rd edition (ICCC-3). We estimated incidence and distribution of cases by ICCC-3 cancer site, comparing between the time periods 1969-1996 and 1997-2016. We assessed 12-month and 5-year cause-specific survival, and examined differences over the time period, adjusted for age, sex, and ICCC-3 site. RESULTS: Incidence rates of pediatric cancers increased between 1969 and 1996 (n = 134) and 1997 and 2016 (n = 186) among Alaska Native people, from 139.8 in 1 000 000 (95% CI, 116.99-165.7) to 197.54 in 1 000 000 (95% CI, 170.1-228.1). Distribution of ICCC-3 sites differed between time periods (P < .0001). Finally, cancer survival was high; the 12-month survival probability from all ICCC-3 sites combined was 0.88 (95% CI, 0.84-0.92) and the 5-year survival probability was 0.76 (95% CI, 0.70-0.81) for 1969-2016. After adjusting for age, sex, and ICCC-3 site, we observed a 57% decrease in the risk of death when comparing Alaska Native pediatric cancer cases diagnosed in 1997-2016 with those diagnosed in 1969-1996. CONCLUSIONS: This information will be of value for our understanding of pediatric cancers among Indigenous peoples of the US, and will also be informative for clinicians providing care to this population.

Incorporating Participant and Clinical Feedback into a Community-Based Participatory Research Study of Colorectal Cancer Among Alaska Native People.

Alaska Native (AN) people have among the highest rates of colorectal cancer (CRC) globally. We are developing a community-based participatory research (CBPR) informed program to understand risk and protective factors contributing to these high rates. In 2018, we conducted a pilot study to test feasibility of recruiting participants from the Alaska Native Medical Center CRC Screening Clinic into a prospective epidemiologic study. Post-pilot study completion, we conducted focus groups (n = 2) with participants and key informant interviews (n = 7) with research and clinical staff to understand study experiences. During 106 days of recruitment, 30 participants enrolled in the pilot study. Over half (60%) were female, and most (67%) were aged 40-59 years. Key themes that emerged from the participant focus groups were: the desire to contribute to improving the health of AN people as a key driver of participation; an overall positive experience with the study; the benefit of clinical staff notifying patients about the study; the need to clearly explain the purpose of each biospecimen collected; barriers to participation; and, the importance of returning study results to the community. Key themes from research and clinical staff interviews included: the study not interfering with clinical duties; the importance of relationships between clinical and research staff; the importance of research staff flexibility; and, comments on specific study procedures. As part of the CBPR process, this feedback will be incorporated into study protocols. We are building this pilot work into a larger prospective study that will inform primary prevention programs.

Cancer incidence and associations with known risk and protective factors: the Alaska EARTH study.

PURPOSE: Cancer is the leading cause of mortality among Alaska Native (AN) people. The Alaska Education and Research Towards Health (EARTH) cohort was established to examine risk and protective factors for chronic diseases, including cancer, among AN people. Here, we describe the cancer experience of the Alaska EARTH cohort in relation to statewide- and region-specific tumor registry data, and assess associations with key cancer risk factors. METHODS: AN participants were recruited into the Alaska EARTH cohort during 2004-2006. Data collected included patient demographic, anthropometric, medical and family history, and lifestyle information. This study linked the Alaska EARTH data with cancer diagnoses recorded by the Alaska Native Tumor Registry (ANTR) through 12/31/15. We compared EARTH incidence to ANTR statewide incidence. We examined independent associations of smoking status, diet, BMI, and physical activity with incident all-site cancers using multivariable-adjusted Cox proportional hazards models. RESULTS: Between study enrollment and 2015, 171 of 3,712 (4.7%) Alaska EARTH study participants were diagnosed with cancer. The leading cancers among Alaska EARTH participants were female breast, lung, and colorectal cancer, which reflected those observed among AN people statewide. Incidence (95% CI) of cancer (all sites) among Alaska EARTH participants was 629.7 (510.9-748.6) per 100,000 person-years; this was comparable to statewide rates [680.5 (660.0-701.5) per 100,000 population]. We observed lower risk of all-sites cancer incidence among never smokers. CONCLUSIONS: Cancer incidence in the Alaska EARTH cohort was similar to incidence observed statewide. Risk and protective factors for leading cancers among AN people mirror those observed among other populations.

Short-term heat stress impairs testicular functions in the American oyster, Crassostrea virginica: Molecular mechanisms and induction of oxidative stress and apoptosis in spermatogenic cells.

Global temperature is increasing due to anthropogenic activities. Abnormal temperature has devastating effects on growth, reproduction, and development of aquatic organisms. In this study, we examined the effects of short-term exposure to elevated temperatures (28 and 32°C for 1 week) on testicular functions, heat shock protein-70 (HSP70), dinitrophenyl protein (DNP, a biomarker of reactive oxygen species [ROS]), and nitrotyrosine protein (NTP, an indicator of reactive nitrogen species [RNS]) expressions, protein carbonyl (PC, a measure of ROS) contents, nitrates/nitrites (NOx, a metabolite of nitric oxide) levels, extrapallial fluid (EPF) conditions, and cellular apoptosis in American oyster (Crassostrea virginica). Higher temperatures significantly decreased (~26%) sperm production in oysters compared with controls (24°C). HSP70, NTP, and DNP expressions were increased after heat exposure, consistent with increased EPF pH, and cellular apoptosis. The enhanced apoptosis in spermatogenic cells is associated with increased caspase 3/7 activity, PC contents, and NOx levels in testicular tissues. Together these results suggest that elevated temperature drastically increases oxidative stress and cellular apoptosis which in turn leads to decreased testicular functions in oysters. To the best of our knowledge, this study reports the first findings on the impacts of elevated temperatures on testicular functions in oysters.

The Nitrogen Isotope Ratio Is a Biomarker of Yup'ik Traditional Food Intake and Reflects Dietary Seasonality in Segmental Hair Analyses.

BACKGROUND: The nitrogen isotope ratio (NIR) is a promising index of traditional food intake for an Alaska Native (Yup'ik) population, which can be measured in blood and hair. However, the NIR has not been calibrated to high-quality measures of Yup'ik traditional food intake. OBJECTIVES: Our primary objective was to examine associations between intakes of Yup'ik traditional food groups, including fish, marine mammals, birds, land mammals, berries, greens, and total traditional foods, and the NIR. In an exploratory analysis, we also examined whether NIR analyzed sequentially along hair could reflect dietary seasonality. METHODS: We recruited 68 participants from 2 Yup'ik communities in the Yukon Kuskokwim region of Southwest Alaska (49% female, aged 14-79 y). Participants completed 4 unscheduled 24-h food recalls over the period peak of RBC and hair synthesis preceding a specimen collection visit. The NIR was measured in RBCs ( n = 68), a proximal hair section (n = 58), and sequential segments of hair from individuals in the upper 2 quartiles of traditional food intake having hair >6 cm in length, plus 2 low subsistence participants for reference (n = 18). Diet-biomarker associations were assessed using Pearson's correlation and linear regression. RESULTS: Intakes of fish, marine mammals, berries, and greens were significantly associated with the NIR. The strongest dietary association was with total traditional food intake (R2 = 0.62), which indicated that each 1‰ increase in the RBC NIR corresponded to 8% of energy from traditional foods. Hair NIR appeared to fluctuate seasonally in some individuals, peaking in the summertime. CONCLUSIONS: Findings support the use of the RBC and hair NIR to assess total traditional food intake in a Yup'ik population. Analyses of sequential hair NIR provided evidence of seasonality in traditional food intake, although seasonal variations were modest relative to interindividual variation.

Developing an Epidemiologic Study to Investigate Risk Factors for Colorectal Cancer Among Alaska Native People.

Alaska Native (AN) people have among the highest rates of colorectal cancer (CRC) recorded globally. Preventing CRC is an important health priority of AN tribal health leaders and communities. Lifestyle and genetic risk and protective factors for CRC among AN people remain understudied. We have been working to establish a tribally led, community-based, comprehensive investigation of lifestyle and genetic risk and protective factors for CRC among AN people. We describe the process of initiating this research study, including conversations with key tribal health system staff. We discuss themes that arose during these conversations and literature review and describe how those themes were used during the study design and protocol development phase. This description is intended to provide guidance to other researchers working to establish community-based studies of cancer risk, particularly among tribal communities.