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

PUBLISHED 06 April 2023Background: 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.Kazzem Gheybi, Elizabeth Buckley, Agnes Vitry and David Rode

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

The Non-Coding RNA Journal Club: Highlights on Recent Papers—6

We are delighted to share with you our sixth Journal Club and highlight some of the most interesting papers published recently [...

Nitroxide mediated and atom transfer radical graft polymerization of atactic polymers onto syndiotactic polystyrene

'Living' radical graft polymerization was employed to prepare graft copolymers with nitroxide-mediated arylated syndiotactic polystyrene as the backbone and polystyrene (PS), poly(p-methylstyrene) (PMS) and poly(methylmethacrylate) (PMMA) as branches. A two-stage process has been developed to synthesize the macroinitiator. First, syndiotactic polystyrene (sPS) was modified by the Friedel-Crafts reaction to introduce chlorine; second, the chlorine groups were converted to nitroxide mediated groups by coupling with 1-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO-OH). The resulting macroinitiator (sPS-TEMPO) for 'living' free radical polymerization was then heated in the presence of styrene and p-methylstyrene to form graft and block copolymers. We used the obtained copolymer and N-bromosuccinimide as brominating agent to achieve polymers with bromine groups. This brominated copolymer was used as a macroinitiator for polymerizing methyl methacrylate in the presence of the CuBr/bpy catalyst system. The formation of the graft and block copolymers was confirmed by DSC, ¹H NMR and FTIR spectroscopy. This approach using macroinitiators is an effective method for the preparation of new materials