Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

A hallmark feature of inflammation is the orchestrated recruitment of neutrophils from the bloodstream into inflamed tissue. Although selectins and integrins mediate recruitment in many tissues, they have a minimal role in the lungs and liver. Exploiting an unbiased in vivo functional screen, we identified a lung and liver homing peptide that functionally abrogates neutrophil recruitment to these organs. Using biochemical, genetic, and confocal intravital imaging approaches, we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration independent of its enzymatic activity. Importantly, genetic ablation or functional peptide blocking of DPEP1 significantly reduced neutrophil recruitment to the lungs and liver and provided improved survival in models of endotoxemia. Our data establish DPEP1 as a major adhesion receptor on the lung and liver endothelium and identify a therapeutic target for neutrophil-driven inflammatory diseases of the lungs.

Assessing Breast Cancer Screening and Outcomes Among First Nations Women in Alberta.

BACKGROUND: Breast cancer (BC) incidence rates for First Nations (FN) women in Canada have been steadily increasing and are often diagnosed at a later stage. Despite efforts to expand the reach of BC screening programs for FN populations in Alberta (AB), gaps in screening and outcomes exist. METHODS: Existing population-based administrative databases including the AB BC Screening Program, the AB Cancer Registry, and an AB-specific FN registry data were linked to evaluate BC screening participation, detection, and timeliness of outcomes in this retrospective study. Tests of proportions and trends compared the findings between FN and non-FN women, aged 50-74 years, beginning in 2008. Incorporation of FN principles of ownership, control, access, and possession (OCAP®) managed respectful sharing and utilization of FN data and findings. RESULTS: The average age-standardized participation (2013-8) and retention rates (2015-6) for FN women compared to non-FN women in AB were 23.8% (P < .0001) and 10.3% (P = .059) lower per year, respectively. FN women were diagnosed with an invasive cancer more often in Stage II (P-value = .02). Following 90% completion of diagnostic assessments, it took 2-4 weeks longer for FN women to receive their first diagnosis as well as definitive diagnoses than non-FN women. CONCLUSION: Collectively, these findings suggest that access to and provision of screening services for FN women may not be equitable and may contribute to higher BC incidence and mortality rates. Collaborations between FN groups and screening programs are needed to eliminate these inequities to prevent more cancers in FN women.

The Alberta moving beyond breast cancer (AMBER) cohort study: baseline description of the full cohort.

PURPOSE: The Alberta Moving Beyond Breast Cancer (AMBER) Study is an ongoing prospective cohort study investigating how direct measures of physical activity (PA), sedentary behavior (SB), and health-related fitness (HRF) are associated with survival after breast cancer. METHODS: Women in Alberta with newly diagnosed stage I (≥ T1c) to IIIc breast cancer were recruited between 2012 and 2019. Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak); upper and lower body muscular strength and endurance; dual-X-ray absorptiometry to measure body composition; and questionnaires to measure self-reported PA and SB. RESULTS: At baseline, the 1528 participants' mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%. CONCLUSION: We have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.

Health-Related and Behavioral Factors Associated With Lung Cancer Stage at Diagnosis: Observations From Alberta's Tomorrow Project.

BACKGROUND: Lung cancer is the leading cause of cancer death in Canada, with stage at diagnosis among the top predictors of lung cancer survival. Identifying factors associated with stage at diagnosis can help reduce lung cancer morbidity and mortality. This study used data from a prospective cohort study of adults living in Alberta, Canada to examine factors associated with lung cancer stage at diagnosis. METHODS: This cohort study used data from adults aged 35-69 years enrolled in Alberta's Tomorrow Project. Partial Proportional Odds models were used to examine associations between sociodemographic characteristics and health-related factors and subsequent lung cancer stage at diagnosis. RESULTS: A total of 221 participants (88 males and 133 females) developed lung cancer over the study period. Nearly half (48.0%) of lung cancers were diagnosed at a late stage (stage IV), whereas 30.8 % and 21.3% were diagnosed at stage I/II and III, respectively. History of sunburn in the past year was protective against late-stage lung cancer diagnosis (odds ratio (OR) .40, P=.005). In males, a higher number of lifetime prostate specific antigen tests was associated with reduced odds of late-stage lung cancer diagnosis (odds ratio .66, P=.02). Total recreational physical activity was associated with increased odds of late-stage lung cancer diagnosis (OR 1.08, P=.01). DISCUSSION: Lung cancer stage at diagnosis remains a crucial determinant of prognosis. This study identified important factors associated with lung cancer stage at diagnosis. Study findings can inform targeted cancer prevention initiatives towards improving early detection of lung cancer and lung cancer survival.

Post-diagnosis alcohol intake and prostate cancer survival: A population-based cohort study.

Alcohol consumption has been declared a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) and is a potential risk factor for several types of cancer mortality. However, evidence for an association with prostate cancer survival remains inconsistent. We examined how alcohol consumption post-diagnosis was associated with survival after prostate cancer diagnosis. Men diagnosed with prostate cancer (n = 829) in Alberta, Canada between the years 1997 and 2000 were recruited into a population-based case-control study and then followed for up to 19 years for survival outcomes. Pre- and post-diagnosis alcohol consumption, clinical characteristics and lifestyle factors were collected through in-person interviews shortly after diagnosis and again 2-3 years post-diagnosis. Cox proportional hazards were used to examine how post-diagnosis alcohol consumption was associated with all-cause and prostate cancer-specific mortality (competing risk analysis too), in addition to first recurrence/progression or new primary cancer. Most participants reported drinking alcohol (≥once a month for 6 months) post-diagnosis (n = 589, 71.0%). Exceeding Canadian Cancer Society (CCS) alcohol consumption recommendations (≥2 drinks/day) post-diagnosis was associated with prostate cancer-specific mortality relative to non-drinkers (aHR: 1.82, 95% CI: 1.07-3.10) with borderline evidence of a linear trend. Interestingly, those in the highest quartile of drinks/week pre- and post-diagnosis also had a twofold increase for prostate-specific mortality (aHR: 2.67, 95% CI: 1.28-5.56) while controlling for competing risks. Our results support post-diagnosis alcohol consumption was associated with increased mortality after prostate cancer diagnosis, specifically for prostate cancer-related death. Future studies focused on confirming this burden of disease are warranted.

Anthropometric measurements and survival after a prostate cancer diagnosis.

BACKGROUND: Evidence regarding the role of anthropometrics in prostate cancer survival is inconsistent. We examined the associations between anthropometric measures and survival outcomes. METHODS: Men diagnosed with prostate cancer (n=987) were recruited into a population-based case-control study between 1997 and 2000 then a prospective cohort study between 2000 and 2002 where anthropometric measurements (weight, height, body mass index, waist circumference, waist-hip ratio) were taken and participants were followed up to 19 years for survival outcomes. Cox proportional hazards were used to examine these associations. RESULTS: Survival analyses suggested no clear pattern of associations between post-diagnosis anthropometric measurements and all-cause mortality, prostate-specific mortality, first recurrence/progression or new primary cancer. CONCLUSIONS: We did not find a significant trend relating anthropometrics to survival outcomes after prostate cancer diagnosis. Continued assessment of objective measurements of body composition over the life-course is warranted to determine true associations between anthropometrics and survival after prostate cancer.

A quantitative multimodal metabolomic assay for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

Identification and prediction of health-related quality of life trajectories after a prostate cancer diagnosis.

The aim of our study was to identify physical and mental health-related quality of life (HRQoL) trajectories after a prostate cancer diagnosis and systematically characterize trajectories by behaviours and prognostic factors. Prostate cancer survivors (n = 817) diagnosed between 1997 and 2000 were recruited between 2000 and 2002 into a prospective repeated measurements study. Behavioural/prognostic data were collected through in-person interviews and questionnaires. HRQoL was collected at three post-diagnosis time-points, approximately 2 years apart using the Short Form (SF)-36 validated questionnaire. To identify physical and mental HRQoL trajectories, group-based trajectory modelling was undertaken. Differences between groups were evaluated by assessing influential dropouts (mortality/poor health), behavioural/prognostic factors at diagnosis or during the follow-up. Three trajectories of physical HRQoL were identified including: average-maintaining HRQoL (32.2%), low-declining HRQoL (40.5%) and very low-maintaining HRQoL (27.3%). In addition, three trajectories for mental HRQoL were identified: average-increasing HRQoL (66.5%), above average-declining HRQoL (19.7%) and low-increasing HRQoL (13.8%). In both physical and mental HRQoL, dropout from mortality/poor health differed between trajectories, thus confirming HRQoL and mortality were related. Furthermore, increased Charlson comorbidity index score was consistently associated with physical and mental HRQoL group membership relative to average maintaining groups, while behaviours such as time-varying physical activity was associated with physical HRQoL trajectories but not mental HRQoL trajectories. It was possible to define three trajectories of physical and mental HRQoL after prostate cancer. These data provide insights regarding means for identifying subgroups of prostate cancer survivors with lower or declining HRQoL after diagnosis whom could be targeted for interventions aimed at improving HRQoL.

A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.

BACKGROUND: Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging. METHODS: Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated. RESULTS: A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage. CONCLUSIONS: Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.

The Sedentary Time and Activity Reporting Questionnaire (STAR-Q): reliability and validity against doubly labeled water and 7-day activity diaries.

We determined measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR-Q), which was designed to estimate past-month activity energy expenditure (AEE). STAR-Q validity and reliability were assessed in 102 adults in Alberta, Canada (2009-2011), who completed 14-day doubly labeled water (DLW) protocols, 7-day activity diaries on day 15, and the STAR-Q on day 14 and again at 3 and 6 months. Three-month reliability was substantial for total energy expenditure (TEE) and AEE (intraclass correlation coefficients of 0.84 and 0.73, respectively), while 6-month reliability was moderate. STAR-Q-derived TEE and AEE were moderately correlated with DLW estimates (Spearman's ρs of 0.53 and 0.40, respectively; P < 0.001), and on average, the STAR-Q overestimated TEE and AEE (median differences were 367 kcal/day and 293 kcal/day, respectively). Body mass index-, age-, sex-, and season-adjusted concordance correlation coefficients (CCCs) were 0.24 (95% confidence interval (CI): 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR-Q-derived versus DLW-derived TEE and AEE, respectively. Agreement between the diaries and STAR-Q (metabolic equivalent-hours/day) was strongest for occupational sedentary time (adjusted CCC = 0.76, 95% CI: 0.64, 0.85) and overall strenuous activity (adjusted CCC = 0.64, 95% CI: 0.49, 0.76). The STAR-Q demonstrated substantial validity for estimating occupational sedentary time and strenuous activity and fair validity for ranking individuals by AEE.

Stage Shifting by Modifying the Determinants of Breast Cancer Stage at Diagnosis: A Simulation Study.

BACKGROUND: Breast cancer is the most common cancer in Canadian women; nearly 25% of women diagnosed with cancer have breast cancer. The early detection of breast cancer is a major challenge because tumours often grow without causing symptom. The diagnosis of breast cancer at an early stage (stages I and II) improves survival outcomes because treatments are more effective and better tolerated. To better inform the prevention of and screening for breast cancer, simulations using modifiable rather than non-modifiable risk factors may be helpful in shifting the stage at diagnosis downward. METHODS: Breast cancer stages were simulated using the data distributions from Alberta's Tomorrow Project participants who developed breast cancer. Using multivariable partial proportional odds regression models, modifiable lifestyle factors associated with the stage of cancer at diagnosis were evaluated. The proportions or mean levels of these lifestyle factors in the simulated population were systematically changed, then multiplied by their corresponding estimated odds ratios from the real data example. The effects of these changes were evaluated singly as well as cumulatively. RESULTS: Increasing total dietary protein (g/day) intake was the single most important lifestyle factor in shifting the breast cancer stage downwards followed by decreasing total dietary energy intake (kcal/day). Increasing the proportion of women who spend time in the sun between 11 am and 4 pm in the summer months, who have had a mammogram, who have been pregnant or reducing the proportion who are in stressful situations had much smaller effects. The percentage of Stage I diagnoses could be increased by approximately 12% with small modifications of these lifestyle factors. CONCLUSION: Shifting the breast cancer stage at diagnosis of a population may be achieved through changes to lifestyle factors. This proof of principle study that evaluated multiple factors associated with the stage at diagnosis in a population can be expanded to other cancers as well, providing opportunities for cancer prevention programs to target specific factors and identify populations at higher risk.

Case-control study of lifetime alcohol intake and prostate cancer risk.

PURPOSE: Alcohol consumption may be a modifiable risk factor for prostate cancer, but previous results have been inconsistent and limited by a lack of data on lifetime exposure and specific beverages. Furthermore, the effect of tumor stage and severity of disease on the association between alcohol and prostate cancer risk has not been fully investigated. METHODS: We examined the relation between both current and lifetime alcohol intake and prostate cancer risk in a population-based case-control study in Alberta, Canada with 947 cases with stage T2 and higher prostate cancer diagnosed between 1997 and 2000 and frequency matched to 1,039 controls, identified through random digit dialing. Cases were classified on cancer stage and severity into 619 non-aggressive (Stage II and Gleason score <8) and 328 aggressive cases (Stage III/IV or Gleason score ≥8). In-person interviews were completed on current and lifetime history of alcohol consumption and all other prostate cancer risk factors. RESULTS: Current alcohol intake did not increase prostate cancer risk but lifetime intake increased risk for both non-aggressive and aggressive cases, with an odds ratio of 1.78 (95 % CI 1.19-2.66) and 2.00 (95 % CI 1.19-3.36), respectively, for the highest intake quartile compared to non-drinkers with evidence for a linear trend. Associations with alcohol intake remained after exclusion of non-drinkers for non-aggressive prostate cancer cases. Only lifetime beer intake was significantly associated with increased risk, however, intakes of liquor and wine by participants were low. CONCLUSIONS: Results support the evidence for an increased risk of prostate cancer from lifetime alcohol consumption.

Low Serum Vitamin D Associated With Increased Tumor Size and Higher Grade in Premenopausal Canadian Women With Breast Cancer.

INTRODUCTION: This study investigated the association of Vitamin D with tumor characteristics in pre and postmenopausal women. PATIENTS AND METHODS: A prospective cohort of 476 women with incident stage I-III breast cancer (BC) in Alberta, Canada comprised the study population. Vitamin D was measured as 25(OH)D concentration in serum samples collected at diagnosis (presurgery and prior to treatment initiation). Tumor characteristics including size, grade, receptor status, stage and nodal status were evaluated in regression models for association with Vitamin D and measured cytokines in models adjusted for menopausal status. RESULTS: More than half of the women were diagnosed as stage I and Luminal A/B, most were postmenopausal, had sufficient Vitamin D levels, and were 56.6 years of age on average. Higher vitamin D levels were associated with decreased tumor size for all women with larger effect seen in premenopausal status. Insufficient vitamin D levels were significantly associated with increased risk of higher grade, but only in premenopausal women. Elevated human granulocyte macrophage colony-stimulating factor was an independent risk factor associated with increased risk of higher-grade tumors. CONCLUSION: Women with sufficient Vitamin D levels at BC diagnosis had smaller and lower grade tumors compared to women with insufficient vitamin D, especially among premenopausal women. Maintaining adequate vitamin D levels in premenopausal women could improve prognostically important BC characteristics at diagnosis.

Development and External Validation of Partial Proportional Odds Risk Prediction Models for Cancer Stage at Diagnosis among Males and Females in Canada.

Risk prediction models for cancer stage at diagnosis may identify individuals at higher risk of late-stage cancer diagnoses. Partial proportional odds risk prediction models for cancer stage at diagnosis for males and females were developed using data from Alberta's Tomorrow Project (ATP). Prediction models were validated on the British Columbia Generations Project (BCGP) cohort using discrimination and calibration measures. Among ATP males, older age at diagnosis was associated with an earlier stage at diagnosis, while full- or part-time employment, prostate-specific antigen testing, and former/current smoking were associated with a later stage at diagnosis. Among ATP females, mammogram and sigmoidoscopy or colonoscopy were associated with an earlier stage at diagnosis, while older age at diagnosis, number of pregnancies, and hysterectomy were associated with a later stage at diagnosis. On external validation, discrimination results were poor for both males and females while calibration results indicated that the models did not over- or under-fit to derivation data or over- or under-predict risk. Multiple factors associated with cancer stage at diagnosis were identified among ATP participants. While the prediction model calibration was acceptable, discrimination was poor when applied to BCGP data. Updating our models with additional predictors may help improve predictive performance.

Health-Related and Psychosocial Factors Associated with Prostate Cancer Stage at Diagnosis among Males Participating in Alberta's Tomorrow Project.

Prostate cancer (PCa) stage at diagnosis is an important predictor of cancer prognosis. In Canada, over one-quarter of males are diagnosed with advanced-stage PCa. Studies have identified several factors associated with PCa stage at diagnosis; however, evidence from Canada is limited. This study aimed to examine associations between sociodemographic characteristics, health history, health practices, and psychosocial factors and PCa stage at diagnosis among males participating in Alberta's Tomorrow Project (ATP), a prospective cohort in Alberta, Canada. The study included males aged 35-69 years who developed PCa until January 2018. Factors associated with PCa stage at diagnosis were examined using partial proportional odds (PPO) ordinal regression models. A total of 410 males were diagnosed with PCa over the study period. A higher number of lifetime prostate-specific antigen tests were associated with earlier-stage PCa (OR 0.91, p = 0.02, 95% CI 0.83-0.99), while higher abdominal circumference (OR 1.02, p = 0.05, 95% CI 1.00-1.03), lower social support (OR 2.34, p < 0.01, 95% CI 1.31-4.17), and having children (OR 2.67, p < 0.01, 95% CI 1.38-5.16) were associated with later-stage disease. This study identified factors previously found in the literature as well as novel factors associated with PCa stage at diagnosis, which can help inform targets for cancer prevention programs to improve PCa prognosis.

Clinical and metabolomic characterization of Brivanib-Induced hypertension in metastatic colorectal cancer.

BACKGROUND: Trials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome. PATIENTS AND METHODS: Clinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA). RESULTS: In the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R2 Y score = 0.89, Q2 Y score = 0.70, CV-ANOVA = 2.01 e-7). Notable metabolomic features previously reported in pre-eclampsia and associated with vasoconstriction were found. CONCLUSION: TKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.

Creation of a Métis-Specific Instrument for Cancer Screening: A Scoping Review of Cancer-Screening Programs and Instruments.

Understanding the barriers to and facilitators of cancer screening programs among Indigenous populations remains limited. In the spirit of mutual respect, this co-led, collaborative project was carried out between the Métis Nation of Alberta and Screening Programs from Alberta Health Services (AHS). This scoping review assessed the cancer screening literature for available questionnaires and then identified themes and suitable questions for a Métis-specific cancer screening questionnaire. Literature searches on cervical, breast, and colorectal cancer screening programs and related concepts were conducted in electronic databases, including the Native Health Database, MEDLINE (Ovid), PsycINFO, PubMed, PubMed Central, CINAHL, MEDLINE (Ebsco), Psychology & Behavioral Sciences Collection, and Web of Science. Grey literature was collected from AHS Insite, Open Archives Initiative repository, American Society of Clinical Oncology, European Society of Medical Oncology, Google, and Google Scholar. 135 articles were screened based on the eligibility criteria with 114 articles selected, including 14 Indigenous-specific ones. Knowledge, attitude, belief, behaviour, barrier, and facilitator themes emerged from the review, but no Métis-specific cancer screening instruments were found. Thus, one was developed using existing cancer screening instruments, with additional questions created by the project team. A survey of the Métis population in Alberta will use this questionnaire and provide data to address the burden of cancer among Métis people.

Pre-diagnosis lifestyle, health history and psychosocial factors associated with stage at breast cancer diagnosis - Potential targets to shift stage earlier.

BACKGROUND: Early detection of breast cancer improves survival, so identifying factors associated with stage at diagnosis may help formulate cancer prevention messages tailored for higher risk women. The goal of this study was to evaluate associations between multiple potential risk factors, including novel ones, measured before a breast cancer diagnosis and stage at diagnosis in women from Alberta, Canada. METHODS: Women enrolled in Alberta's Tomorrow Project completed health and lifestyle questionnaires on average 7 years before their breast cancer diagnosis. The association of previously identified and novel predictors with stage (I, II and III + IV) at diagnosis were simultaneously evaluated in partial proportional odds ordinal (PPO) regression models. RESULTS: The 492 women in this study were predominantly diagnosed in Stage 1 (51.4%), had college or university education (75.4%), were married or had a partner (74.6%), had been pregnant (90.2%), had taken birth control pills for any reason (86.8%), and had an average body mass index of 26.6. Most had at least one mammogram (83%) with five mammograms the average number. Nearly all reported previously having a breast health examination from a medical practitioner (92.5%). Statistically significant factors identified in the PPO model included protective ones (older age at diagnosis, high household income, parity, smoking, spending time in the sun during high ultraviolet times, having a mammogram and high daily protein intake) and ones that increased risk of later stage at diagnosis (a comorbidity, current stressful situations and high daily caloric intake). CONCLUSION: Shifting breast cancer stage at diagnosis downwards may potentially be achieved through cancer prevention programs that target higher risk groups such as women with co-morbidities, non-smokers and younger women who may be eligible for breast cancer screening.

Comparison of Two Automated Targeted Metabolomics Programs to Manual Profiling by an Experienced Spectroscopist for 1H-NMR Spectra.

Automated programs that carry out targeted metabolite identification and quantification using proton nuclear magnetic resonance spectra can overcome time and cost barriers that limit metabolomics use. However, their performance needs to be comparable to that of an experienced spectroscopist. A previously analyzed pediatric sepsis data set of serum samples was used to compare results generated by the automated programs rDolphin and BATMAN with the results obtained by manual profiling for 58 identified metabolites. Metabolites were selected using Student's t-tests and evaluated with several performance metrics. The manual profiling results had the highest performance metrics values, especially for sensitivity (76.9%), area under the receiver operating characteristic curve (0.90), precision (62.5%), and testing accuracy based on a neural net (88.6%). All three approaches had high specificity values (77.7-86.7%). Manual profiling by an expert spectroscopist outperformed two open-source automated programs, indicating that further development is needed to achieve acceptable performance levels.