Principles and methods for transferring polygenic risk scores across global populations.

Polygenic risk scores (PRSs) summarize the genetic predisposition of a complex human trait or disease and may become a valuable tool for advancing precision medicine. However, PRSs that are developed in populations of predominantly European genetic ancestries can increase health disparities due to poor predictive performance in individuals of diverse and complex genetic ancestries. We describe genetic and modifiable risk factors that limit the transferability of PRSs across populations and review the strengths and weaknesses of existing PRS construction methods for diverse ancestries. Developing PRSs that benefit global populations in research and clinical settings provides an opportunity for innovation and is essential for health equity.

Oncologists' perceived confidence and attitudes toward managing pre-existing chronic comorbidities during patients' active cancer treatment.

PURPOSE: To examine practicing oncologists' perceived confidence and attitudes toward management of pre-existing chronic conditions(PECC) during active cancer treatment(ACT). METHODS: In December 2018, oncologists in the National Cancer Institute's Community Oncology Research Program (NCORP) were invited to complete a was pilot-tested, IRB-approved online survey about their perceived confidence in managing PECC. Pearson chi-square test was used to identify oncologists' differences in perceived confidence to manage PECC and attitudes toward co-management of patients' PECC with non-oncologic care providers. Perceived confidence and attitudes were analyzed as a function of medical specialty while controlling demographic and medical practice variables. RESULTS: A total of 391 oncologists responded to the survey, 45.8% stated medical oncology as their primary specialty, 15.1% hematology oncology, 15.1% radiation oncology, 6.9% surgical oncology, and 17.1% other specialties such as gynecology oncology. Overall, 68.3% agreed (agree/strongly agree) that they were confident to manage PECC in the context of standard of care. However, only 46.6% and 19.7% remained confident when managing PECC previously managed by a primary care physician (PCP) and by a non-oncology subspecialist, respectively. Most oncologists (58.3%) agreed that patients' overall care was well coordinated, and 63.7% agreed that patients had optimal cancer and non-cancer care when PECC was co-managed with a non-oncology care provider. CONCLUSION: Most oncologists felt confident to manage all PECC during patients' ACT, but their perceived confidence decreased for PECC previously managed by PCPs or by non-oncology subspecialists. Additionally, they had positive attitudes toward co-management of PECC with non-oncologic care providers. These results indicate opportunities for greater collaboration between oncologists and non-oncology care providers to ensure comprehensive and coordinated care for cancer patients with PECC.

U.S. Maternal Mortality Within a Global Context: Historical Trends, Current State, and Future Directions.

In the United States, despite significant investment and the efforts of multiple maternal health stakeholders, maternal mortality (MM) has reemerged since 1987 and MM disparity has persisted since 1935. This article provides a review of the U.S. MM trajectory throughout its history up to its current state. From this longitudinal perspective, MM trends and themes are evaluated within a global context in an effort to understand the problems and contributing factors. This article describes domestic and worldwide strategies recommended by maternal health stakeholders to reduce MM.

Health Equity Among Black Women in the United States.

Black women in the United States have experienced substantial improvements in health during the last century, yet health disparities persist. These health disparities are in large part a reflection of the inequalities experienced by Black women on a host of social and economic measures. In this paper, we examine the structural contributors to social and economic conditions that create the landscape for persistent health inequities among Black women. Demographic measures related to the health status and health (in)equity of Black women are reviewed. Current rates of specific physical and mental health outcomes are examined in more depth, including maternal mortality and chronic conditions associated with maternal morbidity. We conclude by highlighting the necessity of social and economic equity among Black women for health equity to be achieved.

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors.

INTRODUCTION AND OBJECTIVE: Studies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. METHODS: We recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. RESULTS: Black and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. CONCLUSIONS: Black race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Prostate-Specific Antigen Testing Initiation and Shared Decision-Making: Findings from the 2000 and 2015 National Health Interview Surveys.

PURPOSES: Despite recommendations against prostate cancer screening with prostate-specific antigen (PSA) tests, about one-fourth of men age ≥40 years received PSA tests in 2015. This study aimed to answer 3 questions for men who had a PSA test in the past year: (1) What percentage of these men received the test first suggested by physicians? (2) What factors were associated with physician-initiated PSA testing (PIPT) versus patient/someone else-initiated testing? (3) What percentage of patients ever had shared decision-making when tests were initiated by physicians? METHODS: We analyzed the 2000 and 2015 National Health Interview Survey data. We calculated age-standardized prevalence of PIPT for both years. For 2015, we used logistic regression to calculate adjusted prevalence ratios for PIPT. We also calculated the prevalence of ever discussing both advantages and disadvantages. RESULTS: The age-standardized prevalence of PIPT was significantly higher in 2015 (84.9%) than in 2000 (72.3%). In 2015, nearly 90% of PSA screenings for men aged ≥70 years were suggested by physicians. PIPT was positively associated with 2 or more comorbid conditions and number of patient visits to the doctor. Less than one-third of men reported they had ever participated in a discussion of advantages and disadvantages of PSA testing. CONCLUSIONS: The majority of men who had PSA testing in the past year reported that their physicians were the first to suggest testing, including men aged ≥70 years. Our study also points to the challenges and needs in conducting shared decision-making before PSA testing in clinical practice.

Are HIV-infected men vulnerable to prostate cancer treatment disparities?

BACKGROUND: HIV-infected (HIV(+)) men face cancer treatment disparities that impact outcome. Prostate cancer treatment and treatment appropriateness in HIV(+) men are unknown. METHODS: We used electronic chart review to conduct a retrospective cohort study of 43 HIV(+) cases with prostate cancer and 86 age- and race-matched HIV-uninfected (HIV(-)) controls with prostate cancer, ages 40 to 79 years, from 2001 to 2012. We defined treatment appropriateness using National Comprehensive Cancer Network guidelines and the Charlson comorbidity index (CCI) to estimate life expectancy. RESULTS: Median age was 59.5 years at prostate cancer diagnosis. Median CD4(+) T-cell count was 459.5 cells/mm(3), 95.3% received antiretroviral therapy, and 87.1% were virally suppressed. Radical prostatectomy was the primary treatment for 39.5% of HIV(+) and 71.0% of HIV(-) men (P = 0.004). Only 16.3% of HIV(+) versus 57.0% of HIV(-) men received open radical prostatectomy (P < 0.001). HIV(+) men received more radiotherapy (25.6% vs. 16.3%, P = 0.13). HIV was negatively associated with open radical prostatectomy (OR = 0.03, P = 0.007), adjusting for insurance and CCI. No men were undertreated. Fewer HIV(+) men received appropriate treatment (89.2% vs. 100%, P = 0.003), due to four overtreated HIV(+) men. Excluding AIDS from the CCI still resulted in fewer HIV(+) men receiving appropriate treatment (94.6% vs. 100%, P = 0.03). CONCLUSION: Prostate cancer in HIV(+) men is largely appropriately treated. Under- or overtreatment may occur from difficulties in life expectancy estimation. HIV(+) men may receive more radiotherapy and fewer radical prostatectomies, specifically open radical prostatectomies. IMPACT: Research on HIV/AIDS survival indices and etiologies and outcomes of this prostate cancer treatment disparity in HIV(+) men are needed.

Cancer incidence in Ghana, 2012: evidence from a population-based cancer registry.

BACKGROUND: Data on cancers is a challenge in most developing countries. Population-based cancer registries are also not common in developing countries despite the usefulness of such registries in informing cancer prevention and control programmes. The availability of population-based data on cancers in Africa varies across different countries. In Ghana, data and research on cancer have focussed on specific cancers and have been hospital-based with no reference population. The Kumasi Cancer Registry was established as the first population-based cancer registry in Ghana in 2012 to provide information on cancer cases seen in the city of Kumasi. METHODS: This paper reviews data from the Kumasi Cancer Registry for the year 2012. The reference geographic area for the registry is the city of Kumasi as designated by the 2010 Ghana Population and Housing Census. Data was from all clinical departments of the Komfo Anokye Teaching Hospital, Pathology Laboratory Results, Death Certificates and the Kumasi South Regional Hospital. Data was abstracted and entered into Canreg 5 database. Analysis was conducted using Canreg 5, Microsoft Excel and Epi Info Version 7.1.2.0. RESULTS: The majority of cancers were recorded among females accounting for 69.6% of all cases. The mean age at diagnosis for all cases was 51.6 years. Among males, the mean age at diagnosis was 48.4 compared with 53.0 years for females. The commonest cancers among males were cancers of the Liver (21.1%), Prostate (13.2%), Lung (5.3%) and Stomach (5.3%). Among females, the commonest cancers were cancers of the Breast (33.9%), Cervix (29.4%), Ovary (11.3%) and Endometrium (4.5%). Histology of the primary tumour was the basis of diagnosis in 74% of cases with clinical and other investigations accounting for 17% and 9% respectively. The estimated cancer incidence Age Adjusted Standardised Rate for males was 10.9/100,000 and 22.4/100, 000 for females. CONCLUSION: This first attempt at population-based cancer registration in Ghana indicates that such registries are feasible in resource limited settings as ours. Strengthening Public Health Surveillance and establishing more Population-based Cancer Registries will help improve data quality and national efforts at cancer prevention and control in Ghana.

Vitamin D deficiency predicts prostate biopsy outcomes.

PURPOSE: The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination. EXPERIMENTAL DESIGN: Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage. RESULTS: Among European American (EA) men, there was an association of 25-OH D <12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41-9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14-5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D < 20 ng/mL [OR, 2.43 (1.20-4.94); P = 0.01]. AA men demonstrated an association between 25-OH D < 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59-15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52-11.74); P = 0.003]. CONCLUSIONS: In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage.

Smoking and prostate cancer in a multi-ethnic cohort.

BACKGROUND: Prostate cancer (PCa) and smoking-related morbidity disproportionately burdens African American (AA) men. Smoking is associated with high-grade PCa and incidence, but few studies have focused on AA men. This study aims to determine the effect of tobacco-use on odds of PCa and of high-grade PCa in a population of predominantly AA men. METHODS: This is a cross-sectional study evaluating smoking and PCa status in men with incident PCa and screened healthy controls. Altogether, 1,085 men (527 cases and 558 controls), age ≥ 40 years were enrolled through outpatient urology clinics in two US cities from 2001 to 2012. Validated questionnaires were used to gather clinical and socioeconomic data. RESULTS: The cases and controls were predominantly AA (79.9% and 71.3%, respectively, P = 0.01). AA men smoked more frequently (53.4% vs. 47.9%, P < 0.001) and quit less frequently than European American (EA) men (31.5% vs. 40.4%, P = 0.01). AA heavy smokers had increased odds of PCa diagnosis (OR 2.57, 95% CI 1.09, 6.10) and high-grade cancer (OR 1.89, 95% CI 1.03, 3.48) relative to never smokers and light smokers. Among AAs, heavy smokers had lower odds of NCCN low PCa recurrence risk stratification. AA former smokers had a trend for increased odds of high-grade cancer compared to never smokers. The associations between smokings, cancer diagnosis and cancer grade did not reach statistical significance in EA men. CONCLUSION: We found ethnic differences in smoking behavior. Heavy smoking is associated with increased odds of PCa and of higher Gleason grade in AA men.

Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women.

BACKGROUND: Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple-negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women. METHODS: Formalin-fixed, paraffin-embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue. RESULTS: A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2-fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03-5.52, P = .042). CONCLUSIONS: ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER-, PR-, and HER2-defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC.

Predictors of serum vitamin D levels in African American and European American men in Chicago.

Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon cancer. When compared with European American (EA) men, African American (AA) men have increased risk of prostate cancer, but few studies evaluate vitamin D status in AA men. The authors evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation environment. Blood samples were collected from 492 men, aged between 40 and 79 years, from urology clinics at three hospitals in Chicago, along with demographic and medical information, body mass index, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet radiation exposure were assessed using validated questionnaires. The results demonstrated that Black race, cold season of blood draw, elevated body mass index, and lack of vitamin D supplementation increase the risk of vitamin D deficiency. Supplementation is a high-impact, modifiable risk factor. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

Implementation of a percutaneous core needle biopsy training program: results from the University of Michigan-Komfo Anokye Teaching Hospital breast cancer research partnership.

PURPOSE: To describe a training program in percutaneous core needle biopsy implemented in conjunction with a breast cancer research collaboration between the University of Michigan (UM) and the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. METHODS: In July 2007 a Ghana-based training program for performance of core needle biopsy was jointly coordinated by the UM and KATH principal investigators (L.N. and B.A.). This course required less than 1 week for implementation. RESULTS: Following the training course (July 2007 through August 2008), 82 core needle biopsies of breast masses were performed at KATH. Of these, 56 had tissue specimens available for review at UM for comparison with KATH primary pathology reports. Forty-six of the 56 UM-reviewed cases (82%) had a KATH diagnosis of breast cancer; UM pathology review was in agreement with the cancer diagnosis in all 46 cases (100%). Ten of the 56 UM-reviewed cases (18%) had a KATH diagnosis of benign fibroadenoma/fibrocystic breast tissue; UM review was concordant in all ten cases (100% concordance for benign lesions). For the remaining 26 procedures we were unable to retrieve either the KATH pathology report or tissue blocks for UM review. DISCUSSION: The design and implementation of appropriate diagnostic biopsy programs is important for delivery of high-quality, efficient breast cancer care in developing nations. This study demonstrates a successful 1-week training program in percutaneous core needle biopsy for a multidisciplinary group of physicians. Further work is needed for similar programs to accurately identify and classify breast cancer internationally.

African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study.

BACKGROUND: The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease. METHODS: African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/neu expression. RESULTS: The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P=.002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively (P<.001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively (P<.001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n=46) of African Americans and 44.6% (n=29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%). CONCLUSIONS: Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes.

Descriptive epidemiology of selected olfactory tumors.

Olfactory tumors, especially olfactory neuroblastomas (ON) and carcinomas with neuroendocrine differentiation (CND), are extremely rare, and little descriptive epidemiologic information is available. The objective of this study was to more fully describe selected olfactory tumors using a large population-based cancer incidence database. The Surveillance, Epidemiology and End Results (SEER) 9 registries limited-use data were reviewed from 1973 to 2006 for selected nasal cavity (C30.0) and accessory sinus (C31.0-31.9) tumors. Frequencies, incidence rates, and relative survival rates were estimated using SEER*Stat, v6.5.2. The majority of cases were squamous cell carcinoma (SCC), while the incidence of ON was greater than CND. For ON, the incidence was highest in the 60-79 year age group, while for SCC, the incidence was highest in the 80+ year age group. For CND, the incidence leveled off in the oldest age groups. Survival rates were highest for ON (>70% alive at 5 years after diagnosis) and poorest for CND (44% alive at 5 years). Adjuvant radiation therapy did not improve survival over surgery alone in ON. In SCC, survival was worse in patients who received adjuvant radiation compared to patients who had surgery alone. Our analysis confirms some previously published information, and adds new information about the incidence and demographics of ON and CND. In addition, our analysis documents the lack of benefit of adjuvant radiation in ON. It is not feasible to conduct prospective trials in patients with these rare diseases, and the importance of registry data in learning about olfactory tumors is emphasized.