Ten-year cardiovascular risk among cancer survivors: The National Health and Nutrition Examination Survey.

BACKGROUND: Cancer survivors have a higher risk of developing and dying from cardiovascular disease (CVD) compared to the general population. We sought to determine whether 10-year risk of atherosclerotic CVD (ASCVD) is elevated among those with vs. without a cancer history in a nationally representative U.S. sample. METHODS: Participants aged 40-79 years with no CVD history were included from the 2007-2016 National Health and Nutrition Examination Survey. Cancer history was self-reported and 10-year risk of ASCVD was estimated using Pooled Cohort Equations. We used logistic regression to estimate associations between cancer history and odds of elevated (≥7.5%) vs. low (<7.5%) 10-year ASCVD risk. An interaction between age and cancer history was examined. RESULTS: A total of 15,095 participants were included (mean age = 55.2 years) with 12.3% (n = 1,604) reporting a cancer history. Individuals with vs. without a cancer history had increased odds of elevated 10-year ASCVD risk (OR = 3.42, 95% CI: 2.51-4.66). Specifically, those with bladder/kidney, prostate, colorectal, lung, melanoma, or testicular cancer had a 2.72-10.47 higher odds of elevated 10-year ASCVD risk. Additionally, age was an effect modifier: a cancer history was associated with 1.24 (95% CI: 1.19-4.21) times higher odds of elevated 10-year ASCVD risk among those aged 60-69, but not with other age groups. CONCLUSIONS: Adults with a history of self-reported cancer had higher 10-year ASCVD risk. ASCVD risk assessment and clinical surveillance of cardiovascular health following a cancer diagnosis could potentially reduce disease burden and prolong survival, especially for patients with specific cancers and high ASCVD risk.

RANBP9 affects cancer cells response to genotoxic stress and its overexpression is associated with worse response to platinum in NSCLC patients.

Although limited by severe side effects and development of resistance, platinum-based therapies still represent the most common first-line treatment for non-small cell lung cancer (NSCLC). However, a crucial need in the clinical management of NSCLC is represented by the identification of cases sensitive to DNA damage response (DDR)-targeting drugs, such as cisplatin or PARP inhibitors. Here, we provide a molecular rationale for the stratification of NSCLC patients potentially benefitting from platinum compounds based on the expression levels of RANBP9, a recently identified player of the cellular DDR. RANBP9 was found overexpressed by immunohistochemistry (IHC) in NSCLC compared to normal adjacent tissues (NATs) (n = 147). Moreover, a retrospective analysis of 132 platinum-treated patients from the multi-centric TAILOR trial showed that RANBP9 overexpression levels are associated with clinical response to platinum compounds [Progression Free Survival Hazard Ratio (RANBP9 high vs low) 1.73, 95% CI 1.15-2.59, p = 0.0084; Overall Survival HR (RANBP9 high vs low) 1.99, 95% CI 1.27-3.11, p = 0.003]. Accordingly, RANBP9 KO cells showed higher sensitivity to cisplatin in comparison with WT controls both in vitro and in vivo models. NSCLC RANBP9 KO cells were also more sensitive than control cells to the PARP inhibitor olaparib alone and in combination with cisplatin, due to defective ATM-dependent and hyper-activated PARP-dependent DDR. The current investigation paves the way to prospective studies to assess the clinical value of RANBP9 protein levels as prognostic and predictive biomarker of response to DDR-targeting drugs, leading to the development of new tools for the management of NSCLC patients.