Evaluating Germline Testing Panels in Southern African Males With Advanced Prostate Cancer.

BACKGROUND: Germline testing for prostate cancer is on the increase, with clinical implications for risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline testing for patients with metastatic, regional, very-high-risk localized, and high-risk localized prostate cancer. Although African ancestry is a significant risk factor for aggressive prostate cancer, due to a lack of available data no testing criteria have been established for ethnic minorities. PATIENTS AND METHODS: Through deep sequencing, we interrogated the 20 most common germline testing panel genes in 113 Black South African males presenting with largely advanced prostate cancer. Bioinformatic tools were then used to identify the pathogenicity of the variants. RESULTS: After we identified 39 predicted deleterious variants (16 genes), further computational annotation classified 17 variants as potentially oncogenic (12 genes; 17.7% of patients). Rare pathogenic variants included CHEK2 Arg95Ter, BRCA2 Trp31Arg, ATM Arg3047Ter (2 patients), and TP53 Arg282Trp. Notable oncogenic variants of unknown pathogenicity included novel BRCA2 Leu3038Ile in a patient with early-onset disease, whereas patients with FANCA Arg504Cys and RAD51C Arg260Gln reported a family history of prostate cancer. Overall, rare pathogenic and early-onset or familial-associated oncogenic variants were identified in 6.9% (5/72) and 9.2% (8/87) of patients presenting with a Gleason score ≥8 or ≥4 + 3 prostate cancer, respectively. CONCLUSIONS: In this first-of-its-kind study of southern African males, we provide support of African inclusion for advanced, early-onset, and familial prostate cancer genetic testing, indicating clinical value for 30% of current gene panels. Recognizing current panel limitations highlights an urgent need to establish testing guidelines for men of African ancestry. We provide a rationale for considering lowering the pathologic diagnostic inclusion criteria and call for further genome-wide interrogation to ensure the best possible African-relevant prostate cancer gene panel.

Nursing students' experiences of educational discrimination: a qualitative study.

BACKGROUND: Although the need for justice and the elimination of injustice (or discrimination) is now a universally accepted principle, discrimination is still an unpleasant experience for many nursing students. This study aimed to explain the experiences of nursing students of educational discrimination and find out the main factors that cause this feeling. METHODS: This is a qualitative study conducted in the nursing faculty of Shahr-e-Kord and the Iran university of medical science (IUMS) in Iran. Twelve nursing students were selected by purposeful sampling method and data were collected through face-to-face and in-depth interviews with semi-structured questions. All interviews were analyzed according to the content analysis method. RESULTS: Three main themes and ten subcategories appeared. Extracted themes include: "inappropriate behavior of nursing professors (or instructors) " with 3 subcategories (1- discriminatory behavior by nursing professors (or instructors), 2- lack of sufficient self-confidence in nursing professors and transferring it to the student, and 3- the educator role in motivating or eliminating motivation); "Strict rules" with 3 subcategories (1- inequality in implementation of rights and rules among students of different disciplines, 2- differences in compliance with laws and regulations, and 3- nurses are being strictly monitored), and " Lack of nursing professional independence " with 4 subcategories (1- lack of authority, 2- lack of supportive organizations for nurses, 3- lack of proper social status of nursing in society, and 4- the high authority and power of physicians over other disciplines). CONCLUSIONS: In our study, it was shown that nursing students feel the most discrimination in front of medical students. Feelings of discrimination reduce self-confidence in nursing students. Therefore, nursing educators and professors must think of a solution, or at least they should not cause this feeling in them through inappropriate behavior and discriminatory speech and words.

Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men.

Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for African men. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing. Utilising a clinico-methodologically matched African (n = 113) versus European (n = 57) deep-sequenced PCa resource, we interrogated 42,966 high-quality germline SVs using a best-fit pathogenicity prediction workflow. We identified 15 potentially pathogenic SVs representing 12.4% African and 7.0% European patients, of which 72% and 86% met germline testing standard-of-care recommendations, respectively. Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African associated disparity.

Variations in colorectal cancer pattern of care by age and comorbidity in South Australia.

BACKGROUND: Advanced age is associated with decreased likelihood of colorectal cancer treatment. Here, we investigated the extent to which comorbidities are accountable for this lesser treatment. METHODS: Using population-based datasets, the pattern of care among CRC cases in South Australia during 2004-2013 was investigated. Models were used to investigate associations of age with each treatment type, and differences in these associations were explored by comorbidity and cancer site. RESULTS: The presence of comorbidity was associated with a significantly weaker relationship of age with surgery and chemotherapy. The association of age with surgery also varied for colon and rectal primary cancer sites. Individual comorbidity types varied in their associations with each treatment category. For example, dementia was associated with less chemotherapy provision, however, it was not significantly related to the likelihood of surgery. CONCLUSION: This study indicates that the association of age with surgical treatment differed significantly by the CRC subsite. Comorbidity moderated the negative association of age with chemotherapy, and less so, with extent of surgery. Results were novel in indicating associations of multiple individual comorbidity types with CRC treatment modalities. The data suggest that different individual comorbidity types may have different effects on treatment and should be studied separately.

Associations of advanced age with comorbidity, stage and primary subsite as contributors to mortality from colorectal cancer.

Background: Although survival from colorectal cancer (CRC) has improved substantially in recent decades, people with advanced age still have a high likelihood of mortality from this disease. Nonetheless, few studies have investigated how cancer stage, subsite and comorbidities contribute collectively to poor prognosis of older people with CRC. Here, we decided to explore the association of age with mortality measures and how other variables influenced this association. Methods: Using linkage of several administrative datasets, we investigated the risk of death among CRC cases during 2003-2014. Different models were used to explore the association of age with mortality measures and how other variables influenced this association. Results: Our results indicated that people diagnosed at a young age and with lower comorbidity had a lower likelihood of all-cause and CRC-specific mortality. Aging had a greater association with mortality in early-stage CRC, and in rectal cancer, compared that seen with advanced-stage CRC and right colon cancer, respectively. Meanwhile, people with different levels of comorbidity were not significantly different in terms of their increased likelihood of mortality with advanced age. We also found that while most comorbidities were associated with all-cause mortality, only dementia [SHR = 1.43 (1.24-1.64)], Peptic ulcer disease [SHR = 1.12 (1.02-1.24)], kidney disease [SHR = 1.11 (1.04-1.20)] and liver disease [SHR = 1.65 (1.38-1.98)] were risk factors for CRC-specific mortality. Conclusion: This study showed that the positive association of advanced age with mortality in CRC depended on stage and subsite of the disease. We also found only a limited number of comorbidities to be associated with CRC-specific mortality. These novel findings implicate the need for more attention on factors that cause poor prognosis in older people.

Prostate cancer genetic risk and associated aggressive disease in men of African ancestry.

African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men. To further assess for potentially functional common and rare variant associations, here we interrogate 247,780 exomic variants for 798 Black South African men using a case versus control or aggressive versus non-aggressive study design. Notable genes of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for aggressive disease. Our study highlights the need for further inclusion across the African diaspora to establish African-relevant risk models aimed at reducing prostate cancer health disparities.

Linking African ancestral substructure to prostate cancer health disparities.

Prostate cancer (PCa) is a significant health burden in Sub-Saharan Africa, with mortality rates loosely linked to African ancestry. Yet studies aimed at identifying contributing risk factors are lacking within the continent and as such exclude for significant ancestral diversity. Here, we investigate a series of epidemiological demographic and lifestyle risk factors for 1387 men recruited as part of the multi-ethnic Southern African Prostate Cancer Study (SAPCS). We found poverty to be a decisive factor for disease grade and age at diagnosis, with other notably significant PCa associated risk factors including sexually transmitted diseases, erectile dysfunction, gynaecomastia, and vertex or complete pattern balding. Aligned with African American data, Black ethnicity showed significant risk for PCa diagnosis (OR = 1.44, 95% CI 1.05-2.00), and aggressive disease presentation (ISUP ≥ 4: OR = 2.25, 95% CI 1.49-3.40). New to this study, we demonstrate African ancestral population substructure associated PCa disparity, observing increased risk for advanced disease for the southern African Tsonga people (ISUP ≥ 4: OR = 3.43, 95% CI 1.62-7.27). Conversely, South African Coloured were less likely to be diagnosed with aggressive disease overall (ISUP ≥ 3: OR = 0.38, 95% 0.17-0.85). Understanding the basis for PCa health disparities calls for African inclusion, however, lack of available data has limited the power to begin discussions. Here, focusing on arguably the largest study of its kind for the African continent, we draw attention to the contribution of within African ancestral diversity as a contributing factor to PCa health disparities within the genetically diverse region of southern Africa.

Occurrence of comorbidity with colorectal cancer and variations by age and stage at diagnosis.

BACKGROUND: While age and stage at diagnosis are known to affect treatment choices and survival from colorectal cancer (CRC), few studies have investigated the extent to which these effects are influenced by comorbidity. In this study, we describe the occurrence of comorbidity in CRC cases in South Australia and associations of comorbidity with age, stage and the age-stage relationship. Furthermore, we report on the association of individual comorbidities with age and stage at diagnosis. METHODS: The South Australian Cancer Registry (SACR) provided CRC data (C18-C20, ICD-10) for 2004-2013 diagnoses. CRC data were linked with comorbidity data drawn from hospital records and health insurance claims. Logistic regression was used to model associations of comorbidity with age and stage. RESULTS: For the 8462 CRC cases in this study, diabetes, peptic ulcer disease, and previous cancers were the most commonly recorded co-existing conditions. Most comorbidities were associated with older age, although some presented more frequently in younger people. Patients at both ends of the age spectrum (<50 and 80 + years) had an increased likelihood of CRC diagnosis at an advanced stage compared with other ages (50-79 years old). Adjusting for comorbidities moderated the association of older age with advanced stage. Conditions associated with advanced stage included dementia (OR = 1.25 (1.01-1.55)), severe liver disease (OR = 1.68 (1.04-2.70)), and a previous cancer (OR = 1.18 (1.08-1.28)). CONCLUSION: Comorbidities are prevalent with CRC, especially in older people. These comorbidities differ in their associations with age at diagnosis and stage. Dementia and chronic heart failure were associated with older age whereas inflammatory bowel disease and alcohol access were associated with younger onset of the disease. Severe liver disease and dementia were associated with more advanced stage and rheumatic disease with less advanced stage. Comorbidities also interact with age at diagnosis and appear to vary the likelihood of advanced-stage disease. CRC patient have different association of age with stage depending on their comorbidity status.