TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern.

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.

Multinational, Multicenter Evaluation of Prostate Cancer Tissue in Sub-Saharan Africa: Challenges and Opportunities.

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10-6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10-8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10-6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa.

In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10-11 and 3.74×10-2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.

Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men.

The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.

Cross-sectional and longitudinal associations between body flexibility and sarcopenia.

BACKGROUND: The associations between body flexibility and sarcopenia were not well understood. This study aimed to explore the cross-sectional and longitudinal associations of flexibility with sarcopenia. METHODS: Our study selected participants aged 50-80 from the WELL-China cohort and the Lanxi cohort. Participants from the urban area of the Lanxi cohort were followed up 4 years later. Body flexibility was measured by the sit-and-reach test. Muscle mass was evaluated by dual-energy X-ray absorptiometry. Muscle strength was evaluated using handgrip strength. Sarcopenia was defined as having both low muscle mass and low muscle strength. We used multivariable logistic regressions to assess the cross-sectional associations of body flexibility with low muscle mass, low muscle strength and sarcopenia. We also used multivariable logistic regressions to explore the associations of baseline flexibility and 4-year changes in flexibility with incident low muscle mass, low muscle strength and sarcopenia. RESULTS: A total of 9453 participants were enrolled in the cross-sectional study, and 1233 participants were included in the longitudinal analyses. In the cross-sectional analyses, compared with low body flexibility, high body flexibility was inversely associated with low muscle mass (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.68; P < 0.001), low muscle strength (OR, 0.62; 95% CI, 0.55-0.69; P < 0.001) and sarcopenia (OR, 0.52; 95% CI, 0.41-0.65; P < 0.001), and these associations did not differ in different age groups, sex or physical activity levels. In the longitudinal analyses, compared with participants with low body flexibility, participants with high body flexibility had lower risk of the incident low muscle strength (OR, 0.53; 95% CI, 0.38-0.74; P < 0.001) and sarcopenia (OR, 0.36; 95% CI, 0.21-0.61; P < 0.001), but not incident low muscle mass (OR, 0.59; 95% CI, 0.33-1.06; P = 0.076). Every 1-cm increase in flexibility during 4 years was associated with reduced risk of incident low muscle mass (OR, 0.96; 95% CI, 0.93-1.00; P = 0.025), low muscle strength (OR, 0.96; 95% CI, 0.94-0.98; P = 0.002) and sarcopenia (OR, 0.96; 95% CI, 0.93-0.99; P = 0.007). CONCLUSIONS: High flexibility was associated with reduced risk of incident low muscle strength and sarcopenia. Increases in flexibility were associated with reduced risk of incident low muscle mass, low muscle strength and sarcopenia. Flexibility exercises and monitoring the dynamic change of flexibility might be helpful in preventing sarcopenia among adults aged 50 years or over.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer.

There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Overall and central obesity and prostate cancer risk in African men.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99-1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10-2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24-2.29) were positively associated with D'Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Physical activity and stress management during COVID-19: a longitudinal survey study.

OBJECTIVE: Physical activity (PA) during COVID-19 shelter-in-place (SIP) may offset stress. This study examined associations between PA, stress and stress management strategies during SIP. DESIGN AND MAIN OUTCOME MEASURES: Participants (N = 990) from a cohort of Northern California adults completed surveys during early SIP (3/23/20-4/2/20) and mid-SIP (4/24/20-5/8/20). Participants self-reported past-month PA (meeting vs. not meeting guidelines), changes in stress (decreased/unchanged vs. increased) and use (yes/no) of 10 stress management strategies. We tested differences in mid-SIP stress and stress management strategies by PA, and differences in mid-SIP stress by stress management strategies. RESULTS: Compared to participants inactive at mid-SIP, active participants reported less stress (AOR = 0.60 [0.45, 0.81]). Active participants were more likely to manage stress using outdoor PA, indoor PA, yoga/meditation/prayer, gardening, and reading (AORs > 1.42), and less likely to sleep (AOR = 0.65 [0.48, 0.89]) or eat ([AOR = 0.48 [0.35, 0.66]) more. Managing stress using outdoor PA, indoor PA or reading was associated with lower stress; managing stress using TV/movies, sleeping or eating was associated with increased stress (ps < 0.05). CONCLUSIONS: Meeting PA guidelines during SIP was associated with less stress. Inactive participants reported greater sleeping and eating to cope; active participants used active stress management strategies. Engagement in physically active stress management was associated with lower stress.

Associations of park access, park use and physical activity in parks with wellbeing in an Asian urban environment: a cross-sectional study.

BACKGROUND: Relationships between park access, park use, and wellbeing remain poorly understood. The objectives of this study were to investigate: (1) perceived and objective park access in relation to park use and physical activity in parks; and; (2) perceived and objective park access, park use and physical activity in parks and their associations with wellbeing. METHODS: An interviewer-assisted survey collected data on perceived time to walk to parks, park use time, park physical activity time and wellbeing (using a scale containing nine domains) amongst adult participants of the Singapore Multi-Ethnic Cohort. Geospatial maps of parks and the "walkable" street networks were created for the city-state of Singapore to objectively determine distances to accessible points on park boundaries. Multiple linear regression models estimated the importance of park access to park use and associations of park access and park use with wellbeing, adjusting for potential confounders. RESULTS: Participants' (n = 3435) average age was 48.8 years (SD, 12.8), 44.8% were male and 72.6% were of Chinese ethnicity. Better perceived but not true park access was significantly associated with greater park use. Park access (perceived or true) was not associated with physical activity time in parks. Greater participant park time and physical activity time in parks were associated with higher wellbeing scores (p < 0.001). The differences in wellbeing scores between the reference groups, who spent negligible time in parks, and the highest quartiles of time in parks (10.8 h/month) and physical activity in parks (8.3 h/month) were 3.2 (95% CI 2.1-4.4) and 4.2 (95% CI 4.1-6.3) points out of 100 respectively. These associations were similar for most domains of wellbeing, with clear dose-response relationships. CONCLUSIONS: While perceived park access was strongly associated with park use and well-being, true park access was not, and neither park access measure was associated with park physical activity. Future studies could investigate the influence of park attributes on park use, physical activity in parks and wellbeing. The consistent associations of park use and particularly physical activity in parks with wellbeing suggest that promoting park use, and especially physical activity in parks, is a promising strategy for improving wellbeing in urban settings.

Soluble cluster of differentiation 14 levels elevated in bile from gallbladder cancer cases from Shanghai, China.

Elevated systemic levels of soluble cluster of differentiation 14 (sCD14) have been associated with gallbladder cancer (GBC), but the association with sCD14 levels within the gallbladder has not been investigated. Here, we evaluated sCD14 in the bile of 41 GBC cases and 117 gallstone controls with data on 65 bile inflammation markers. We examined the relationship between bile sCD14 levels and GBC using logistic regression and stratified the analysis by stage. We included GBC-associated inflammatory biomarkers in the model to evaluate the influence of local inflammation. Bile sCD14 levels (third versus first tertile) were associated with GBC (adjusted odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.2-8.0). The association was equally strong for stage I/II (OR: 3.3, 95% CI: 0.9-15.6) and stage III/IV (OR: 3.2, 95% CI: 1.0-12.4) cancers. Including the GBC-associated inflammatory markers in the model removed the association between bile sCD14 and GBC (OR: 1.0, 95% CI: 0.3-3.5). The findings suggest that immune activation within the gallbladder may be related to GBC development, and the effect of sCD14 is influenced by inflammation. Similar associations across tumor stages suggest that elevated bile sCD14 levels may reflect changes early in GBC pathogenesis. Associations between GBC and sCD14 levels in both bile and plasma suggest sCD14 could be a potential biomarker for GBC.

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes.

BACKGROUND & AIMS: Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterise GBC and explore molecular subtypes associated with patient survival. METHODS: We profiled the mutational landscape of GBC tumours (whole-exome sequencing on 92, targeted sequencing on 98, in total 190 patients). In a subset (n = 45), we interrogated the matched transcriptomes, DNA methylomes, and somatic copy number alterations. We explored molecular subtypes identified through clustering tumours by genes whose expression was associated with survival in 47 tumours and validated subtypes on 34 publicly available GBC cases. RESULTS: Exome analysis revealed TP53 was the most mutated gene. The overall mutation rate was low (median 0.82 Mut/Mb). APOBEC-mediated mutational signatures were more common in tumours with higher mutational burden. Aflatoxin-related signatures tended to be highly clonal (present in ≥50% of cancer cells). Transcriptome-wide survival association analysis revealed a 95-gene signature that stratified all GBC patients into 3 subtypes that suggested an association with overall survival post-resection. The 2 poor-survival subtypes were associated with adverse clinicopathologic features (advanced stage, pN1, pM1), immunosuppressive micro-environments (myeloid-derived suppressor cell accumulation, extensive desmoplasia, hypoxia) and T cell dysfunction, whereas the good-survival subtype showed the opposite features. CONCLUSION: These data suggest that the tumour micro-environment and immune profiles could play an important role in gallbladder carcinogenesis and should be evaluated in future clinical studies, along with mutational profiles. LAY SUMMARY: Gallbladder cancer is highly fatal, and its causes are poorly understood. We evaluated gallbladder tumours to see if there were differences between tumours in genetic information such as DNA and RNA. We found evidence of aflatoxin exposure in these tumours, and immune cells surrounding the tumours were associated with survival.

Overall and abdominal obesity and prostate cancer risk in a West African population: An analysis of the Ghana Prostate Study.

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m2 for cases and 24.3 kg/m2 for controls. After adjustment, men with BMI ≥ 30 kg/m2 had an increased risk of prostate cancer relative to men with BMI < 25 kg/m2 (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region.

A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Establishing a Cancer Registry in a Resource-Constrained Region: Process Experience From Ghana.

PURPOSE: In a review of cancer incidence across continents (GLOBOCAN 2012), data sources from Ghana were classified as Frequencies, the lowest classification for inclusion, signifying the worst data quality for inclusion in the analysis. Recognizing this deficiency, the establishment of a population-based cancer registry was proposed as part of a broader cancer control plan. METHODS: The registry was examined under the following headings: policy, data source, and administrative structure; external support and training; and definition of geographic coverage. RESULTS: The registry was set up based on the Ghana policy document on the strategy for cancer control. The paradigm shift ensured subscription to one data collection software (CanReg 5) in the country. The current approach consists of trained registrars based in the registry who conduct active data abstraction at the departments and units of the hospital and pathologic services. To ensure good governance, an administrative structure was created, including an advisory board, a technical committee, and registry staff. External support for the establishment of the Accra Cancer Registry has come mainly from Stanford University and the African Cancer Registry Network, in collaboration with the University of Ghana. Unlike previous attempts, this registry has a well-defined population made up of nine municipal districts. CONCLUSION: The Accra Cancer Registry was established as a result of the lessons learned from failed previous attempts and aim to provide a model for setting up other cancer registries in Ghana. It will eventually be the focal point where all the national data can be collated.

Author Correction: Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

BACKGROUND AND AIMS: Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones. APPROACH AND RESULTS: A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (ORadj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (Pcorrected  < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the ORadj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 ORadj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 ORadj ranging from 0.50 to 0.75 (P < 0.05). CONCLUSIONS: Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

Associations Between Body Fat, Muscle Mass, and Nonalcoholic Fatty Liver Disease: A Population-Based Study.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease worldwide and has emerged as a significant public health concern in China. A better understanding of the etiology of NAFLD can inform effective management strategies for this disease. We examined factors associated with NAFLD in two districts of Hangzhou, China, focusing on the relationship of regional body fat distribution, muscle mass, and NAFLD. We used baseline data to carry out a cross-sectional analysis among 3,589 participants from the Wellness Living Laboratory (WELL) China study, a longitudinal population-based study that aims to investigate and promote well-being among the Chinese population. NAFLD was defined using the widely validated fatty liver index (FLI). Multivariate logistic regressions were performed to assess independent associations between NAFLD and metabolic risk factors (e.g., insulin resistance) and dual x-ray absorptiometry (DXA)-derived measures (e.g., android fat ratio [AFR] and skeletal muscle index [SMI]). Of the 3,589 participants, 476 (13.3%) were classified as having FLI-defined NAFLD (FLI ≥60). Among those, 58.0% were men. According to our analysis, AFR (odds ratio [OR], 10.0; 95% confidence interval [CI], 5.8-18.5), insulin resistance (OR, 4.0; 95% CI, 3.0-5.3), high alanine aminotransferase levels (OR, 7.6; 95% CI, 5.8-10.0), smoking (OR, 2.0; 95% CI, 1.4-3.0), and male sex (OR, 2.9; 95% CI, 2.0-4.2) were positively associated with NAFLD risk, while SMI (OR, 0.1; 95% CI, 0.07-0.13) was inversely associated with NAFLD risk. Conclusion: In addition to known metabolic risk factors, DXA-derived AFR and SMI may provide additional insights to the understanding of NAFLD. Interventions that aim to decrease AFR and increase SMI may be important to reduce the burden of NAFLD in this population.