Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma

Abstract

Sleep disorders have emerged as highly prevalent conditions, and along with improved understanding of such disorders, increased attention has gained the evidence that perturbation in sleep architecture and continuity may initiate, exacerbate, or modulate the phenotypic expression of multiple diseases including cancer. Furthermore, obstructive sleep apnea (OSA) has recently been implicated in increased incidence and more adverse prognosis of cancer in humans. This study was designed to confirm the high prevalence of OSA in human malignancies and assess its prognostic relevance in metastatic colorectal carcinomas (mCRCs). A prospective cohort of 52 subjects, affected by solid histologically confirmed metastatic malignancies, was analyzed, and among them, 29 mCRCs were studied for the prognostic role of OSA. OSA was diagnosed in 34.6% (18/52) of patients with a statistically significant difference in apnea-hyponea index between OSA and non-OSA subgroups (14.2 ± 12.2 vs. 2.1 ± 1.5, p < 0.01 ). Consistently, OSA was diagnosed in 34.5% (10/29) of mCRCs with lower rates of first-line therapy disease control in OSA compared to non-OSA patients (60% in OSA vs. 94.7% in non-OSA, p = 0.03 ). Of note, progression-free and overall survival rates were significantly shorter in OSA (respectively, 9 and 22 months) compared non-OSA (20 and 40 months) mCRC patients (HR = 2.63; 95% CI 0.88–7.84, p = 0.01 for PFS; HR = 3.93; 95% CI 1.13–13.73, p < 0.001 for OS). Finally, the multivariate analysis showed that OSA is an independent prognostic factor for PFS p = 0.0076 and OS p = 0.0017 in this cohort. Altogether, these data suggest that OSA is a potential clinical marker predictor of poor prognosis in patients with mCRC.

Don't let sleeping men lie

“…OSA has recently been shown to be associated with an increased risk of malignancy, 19,20 most notably prostate cancer, and related to the degree of oxygen desaturation. The presence of OSA is associated with lower survival rates 21 …”

Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis

“…Based on the previous considerations, in this study we evaluated the expression of different miRNAs in conditions of continuous hypoxia, moderate (2% of oxygen) and marked (0.5% of oxygen), to study the possible relationship between these two types of continuous hypoxia, miRNA, and cancer and identify the miRNAs involved in carcinogenesis that are susceptible to hypoxia. In detail, we evaluated a group of miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145), which are induced by a hypoxic environment, to better understand how continuous hypoxia could change their signature and to identify their eventual role in colorectal cancer (CRC), which is one of the most frequent tumors in women and men [ 8 ].…”

The Burden of Respiratory Alterations during Sleep on Comorbidities in Obstructive Sleep Apnoea (OSA)

“…Overall, several studies have evaluated the correlation of SRBD with cardiovascular disease or the risk of mortality [ 7 , 15 ]. Other studies have assessed the link between SRBD and cancer [ 16 , 17 , 18 , 19 ]. Furthermore, OSA also affects the immune system [ 20 , 21 ], modulation of the pain response [ 22 , 23 ] and systemic inflammation [ 24 ].…”