It has been demonstrated to involve in a variety of disorders, including NAFLD and CRC. Since its discovery, ferroptosis has become one of the most remarkable research topic. Ferroptosis is caused by the imbalance of diverse cellular metabolic processes, while cuproptosis results from copper-induced proteotoxic stress ( Stockwell, 2022 Tsvetkov et al., 2022).
Hence, we speculate that NAFLD may be related to an increased risk of CRN.įerroptosis and cuproptosis are two novel regulated cell death modalities identified recent years. Importantly, several independent risk factors for NAFLD, such as hyperlipidemia, obesity, and diabetes, have also been identified as potential risk factors for CRN ( Assy et al., 2000 Donati et al., 2004). NAFLD is closely associated with insulin resistance, metabolic syndrome (MetS), diabetes, and cardiovascular disease, suggesting that NAFLD is a multi-system disease with extrahepatic complications ( Armstrong et al., 2014 Byrne and Targher, 2015 Chacko and Reinus, 2016). NAFLD is among the most common chronic liver diseases worldwide, with an estimated prevalence of 25.2%, making it a severe public problem that endangers human health ( Younossi et al., 2016). Exploration of more risk factors underlying CRN (particularly CRC) initiation and development is a necessary and efficient way to benefit the prevention, diagnosis, and treatment of CRN.Īs the economy develops, people have changed a lot in their living habits and diet structures, which partly lead to the higher and higher incidence of non-alcoholic fatty liver disease (NAFLD).
Many risk factors such as genetic factor, dietary habit, and the living environment are known to contribute to the occurrence of CRC ( Sclafani et al., 2013 Budhathoki et al., 2015). However, the increase of CRC incidence (especially among younger persons) around the world indicates that severe challenges remain to control CRC.
The development of screening techniques boosts the diagnosis of CRC ( Ladabaum et al., 2020). In the past few decades, the incident of CRC has increased in most countries and is still on the rise ( Sung et al., 2021). CRC has been estimated the third common cancer type, and the second most common cause of cancer-associated mortality worldwide ( Sung et al., 2021). These findings here support that NAFLD is necessary to be considered as an emerging risk factor for CRN.Ĭolorectal neoplasms (CRN) include colorectal adenoma (CRA) and colorectal cancer (CRC), with CRA transformation typically leading to CRC. Ferroptosis and cuproptosis may be the critical links between NAFLD and CRN, respectively. Our meta- and bioinformatics analysis shows that NAFLD increases the risk of CRN. Interestingly, bioinformatics analysis revealed that there were overlap of dysregulated gene sets among NAFLD, CRC, and two recently identified regulated cell death types, ferroptosis and cuproptosis, respectively. There is no close correlation between smoking status of NAFLD patients and CRN. In the subgroup analysis, NAFLD were found to be the independent risk factor of colorectal adenoma (CRA) (OR = 1.29 95% CI = 1.15–1.45 I 2 = 66.4%) and colorectal cancer (CRC) (OR = 1.13 95% CI = 1.12–1.15 I 2 = 69.4%). The results showed that NAFLD is related to an increased risk of CRN (OR = 1.23 95% CI: 1.14–1.32 I 2 = 70.7%, p < 0.001). 14 cohort studies with a total population of 38,761,773 were included for meta-analysis after selection. PubMed, Cochrane Library, and Embase were searched for cohort studies. This study aims at assessing the potential association between non-alcoholic fatty liver disease (NAFLD) and colorectal neoplasms (CRN).
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