Hypertension as a Predictor of Advanced Colorectal Cancer Outcome and Cetuximab Treatment Response

Abstract

Background Adrenergic receptor stimulation is involved in the development of hypertension (htn) and has been implicated in cancer progression and dissemination of metastases in various tumours, including colon cancer. Adrenergic antagonists such as beta-blockers (bbs) demonstrate inhibition of invasion and migration in colon cancer cell lines and have been associated with decreased mortality in colorectal cancer (crc). We examined the association of baseline htn and bb use with overall (os) and progression-free survival (pfs) in patients with pretreated, chemotherapy refractory, metastatic crc (mcrc). We also examined baseline htn as a predictor of cetuximab efficacy.Methods Using data from the Canadian Cancer Trials Group co.17 study [cetuximab vs. best supportive care (bsc)], we coded baseline htn and use of anti-htn medications, including bbs, for 572 patients. The chi-square test was used to assess the associations between those variables and baseline characteristics. Cox regression models were used for univariate and multivariate analyses of os and pfs by htn diagnosis and bb use.Results Baseline htn, bb use, and anti-htn medication use were not found to be prognostic for improved os. Baseline htn and bb use were not significant predictors of cetuximab benefit.Conclusions In chemorefractory mcrc, neither baseline htn nor bb use is a significant prognostic factor. Baseline htn and bb use are not predictive of cetuximab benefit. Further investigation to determine whether baseline htn or bb use have a similarly insignificant impact on prognosis in patients receiving earlier lines of treatment remains warranted.

Genetic Variants of HOTAIR Associated With Colorectal Cancer Susceptibility and Mortality

“…CRC is associated with a variety of factors. Representative factors include hypertension (42,43), folate (44,45), homocysteine (46), and diabetes milieus (47). Thus, treatment strategies and prognostic management methods change.…”

Effects of Antihypertensive Drugs Use on Risk and Prognosis of Colorectal Cancer: A Meta-Analysis of 37 Observational Studies

“…Studies were retrieved by filtering titles and abstracts, and 39 studies were excluded after full text review, and reasons why studies were excluded were listed in Supplementary Table S4 . Ultimately, we included 37 studies for our meta-analysis, including 20 publications concerning cancer risk ( Pahor et al, 1996 ; Michels et al, 1998 ; Rosenberg et al, 1998 ; Tenenbaum et al, 2001 ; Beiderbeck-Noll et al, 2003 ; Boudreau et al, 2008 ; van der Knaap et al, 2008 ; Friedman et al, 2011 ; Hallas et al, 2012 ; Jansen et al, 2012 ; Wang et al, 2012 ; Mansouri et al, 2013 ; Makar et al, 2014 ; Chang et al, 2015 ; Lin et al, 2015 ; Numbere et al, 2015 ; Grimaldi-Bensouda et al, 2016 ; Dierssen-Sotos et al, 2017 ; Cheung et al, 2020 ; Brasky et al, 2021 ), 17 regarding cancer prognosis ( Sorensen et al, 2000 ; Hicks et al, 2013 ; Holmes et al, 2013 ; Cardwell et al, 2014 ; Jansen et al, 2014 ; Giampieri et al, 2015 ; Osumi et al, 2015 ; Morris et al, 2016 ; Jansen et al, 2017 ; Weberpals et al, 2017 ; Sud et al, 2018 ; Bowles et al, 2019 ; Cui et al, 2019 ; Fiala et al, 2019 ; Mafiana et al, 2019 ; Ozawa et al, 2019 ; Ahl et al, 2020 ). Of these 37 studies, 26 studies used cohort design, three studies used nested case-control design, and 8 studies used case-control design.…”

Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise

“…However, such an effort is currently limited due to the lack of relevant experimental and clinical data about optimal blood pressure control strategy for tumor patients with hypertension. Epidemiological studies in recent years have shown that hypertension was significantly associated with an increased risk of kidney cancer, colon cancer, and postmenopausal breast cancer ( Han et al, 2017 ; Hidayat et al, 2017 ; Sud et al, 2018 ). Similarly, vascular endothelial growth factor signaling pathway inhibitors as common antineoplastic drugs are key contributors to raise blood pressure ( Agarwal et al, 2018 ).…”