Oldvsnew: Risk factors predicting early onset colorectal cancer

Abstract

BACKGROUNDColorectal cancer (CRC) is the second leading cause of all cancer related deaths in the United States and Europe. Although the incidence has been decreasing for individuals’ ≥ 50, it has been on the rise for individuals < 50.AIMTo identify potential risk factors for early-onset CRC.METHODSA population-based cohort analysis using a national database, Explorys, screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC. Subgroups were stratified based on age (25 – 49 years vs ≥ 50 years). Demographics, comorbidities, and symptom profiles were recorded and compared between both age groups. Furthermore, the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC. Twenty-data points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTSA total of 68860 patients were identified with CRC, of which 5710 (8.3%) were younger than 50 years old, with 4140 (73%) between 40-49 years of age. Multivariable analysis was reported using odds ratio (OR) with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group. These factors included: African-American race (OR 1.18, 95%CI: 1.09-1.27, P < 0.001), presenting symptoms of abdominal pain (OR 1.82, 95%CI: 1.72-1.92, P <0.001), rectal pain (OR 1.50, 95%CI: 1.28-1.77, P < 0.001), altered bowel function (OR 1.12, 95%CI: 1.05-1.19, P = 0.0005), having a family history of any cancer (OR 1.78, 95%CI: 1.67-1.90, P < 0.001), gastrointestinal (GI) malignancy (OR 2.36, 95%CI: 2.18-2.55, P < 0.001), polyps (OR 1.41, 95%CI: 1.08-1.20, P < 0.001), and obesity (OR 1.14, 95%CI: 1.08-1.20, P < 0.001). Comparing the early-onset cohort versus the control group, factors that were associated with an increased risk of CRC were: male gender (OR 1.34, 95%CI: 1.27-1.41), P < 0.001), Caucasian (OR 1.48, 95%CI: 1.40-1.57, P < 0.001) and African-American race (OR 1.25, 95%CI: 1.17-1.35, P < 0.001), presenting symptoms of abdominal pain (OR 4.73, 95%CI: 4.49-4.98, P < 0.001), rectal pain (OR 7.48, 95%CI: 6.42-8.72, P < 0.001), altered bowel function (OR 5.51, 95%CI: 5.19-5.85, P < 0.001), rectal bleeding (OR 9.83, 95%CI: 9.12-10.6, P < 0.001), weight loss (OR 7.43, 95%CI: 6.77-8.15, P < 0.001), having a family history of cancer (OR 11.66, 95%CI: 10.97-12.39, P < 0.001), GI malignancy (OR 28.67, 95%CI: 26.64-30.86, P < 0.001), polyps (OR 8.15, 95%CI: 6.31-10.52, P < 0.001), tobacco use (OR 2.46, 95%CI: 2.33-2.59, P < 0.001), alcohol use (OR 1.71, 95%CI: 1.62-1.80, P < 0.001), presence of colitis (OR 4.10, 95%CI: 3.79-4.43, P < 0.001), and obesity (OR 2.88, 95%CI: 2.74-3.04, P < 0.001).CONCLUSIONPending further investigation, these potential risk factors should lower the threshold of suspicion for early CRC and potentially be used to optimize guidelines for early screening.

Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology

“…Gomes et al suggested that increasing the level of SCFAs by manipulating the colon microbiota has the potential to prevent or potentially treat CRC [ 123 ]. Another population-based cohort study (n = 68,860) identified non-modifiable risk factors in early-onset CRC development, such as family or personal history of polyps and rectal bleeding at the time of diagnosis [ 124 ]. In addition, genetic factors, e.g., hereditary CRC syndromes or CRC in first-degree relatives, are associated with higher CRC risk.…”

CircRNA circ-ATAD1 suppresses the maturation of miR-168 to participate in colorectal cancer

“…Treatment of CRC in clinical practice is challenged by the poor prognosis of metastatic cases (5,6). Unfortunately, early diagnosis of CRC is unlikely to be signi cantly improved in near future, mainly owing to the lack of sensitive diagnostic biomarkers.…”

“…However, incidence in young population showed an increasing trend (1,2). Despite the advances in the treatment and prevention of CRC, CRC is still a major cause of cancer deaths all over the world(4), mainly owing to the lack of cures for metastatic CRC and the low early diagnostic rate (5,6). Therefore, novel therapeutic and diagnostic approaches are Smoking, alcohol abuse, poor dietary structure, and and obesity are the major risk factors for CRC (7).…”

Adipose tissue—more than just fat

“…There are also studies that predict a relation between obesity and the risk to develop cancer. 25,26 Nowadays, adipose tissue is not only understood as a fat storage that releases free fatty acids but as a complex endocrine organ that influences hormone balance, metabolic regulation and inflammatory levels, to name just a few. 23 Although the regulatory effects of adipose tissue on oxidative stress, insulin resistance and inflammation are not fully understood (for more reviews see Ref.…”

“…Those clinically relevant outcomes are for example: sleep apnoea‐induced intermittent hypoxia, effects on endothelial cell calcium signalling and alterations in renal sympathic nerve activity. There are also studies that predict a relation between obesity and the risk to develop cancer …”