Increased risk of extra-hepatic neoplasms in NAFLD

29 Nov 2022

We just left October, Breast Cancer Awareness Month, behind us. Throughout the world, many initiatives have been taken in this period to increase attention on what is the most frequent female cancer. It has been known for several years how many preventive measures go through lifestyle, and how, among other things, a balanced diet is associated with a reduction in the incidence of cancer. In non alcoholic fatty liver disease (NAFLD), nutrition is certainly one of the key factors in the prevention and management of the disease. It is therefore natural to wonder if there may be any association between NAFLD and cancer.

It is well known how NAFLD is strictly related to HCC. In fact in 2016, the incidence of HCC among NAFLD patients was 1.8 per 1,000 person-years, and the overall mortality was 5.3 per 1,000 person-years. This data is not only related to patients with advanced fibrosis and cirrhosis, but also to patients with initial fibrosis, that have an incidence rate of 0.03 per 100 person-years [1]. If we consider the vertical increase in the incidence of NAFLD in the world, and in particular in developed countries, we can see how these numbers are certainly worrying. The mechanisms associated with this process are becoming clearer every day: lipotoxicity can worsen insulin resistance and endoplasmic reticulum stress, which leads to a hepatic chronic inflammation, resulting in NASH and liver fibrosis. In this context, immune disorders promote the development of HCC. Moreover, it is believed that other mechanisms could be involved, such as gut inflammation and gut dysbiosis [2-3]. Furthermore, even the close relationship between NAFLD and colorectal cancer is now clear: a 2011 cross-sectional study found the prevalence of advanced colorectal neoplasms was 18.6% in patients with NAFLD vs 5.5% in the control group [4]. Many other studies have reached the same conclusion, leading the guidelines to suggest early screening for these malignancies in patients with NAFLD as risk factor [5].

The concern that this may also involve other districts is well founded, and is dictated by the fact that recent studies have shown that in patients with NAFLD extra-hepatic cancers are among the main causes of mortality [6]. A recent review showed that patients with NAFLD have an increased risk of esophageal, gastric, pancreatic, renal, breast and prostate cancer [7]. The link between breast cancer and NAFLD is even tighter considering that it could be related to different mechanisms: on one hand, NAFLD could increase the risk of developing cancer, while on the other hand chemotherapies such as long-term tamoxifen therapy may increase the risk of NAFLD [8]. 

A Chinese group recently tried to develop a risk-stratification scoring system for predicting risk of breast cancer based on NAFLD, non-alcoholic fatty pancreas disease, and uric acid concentration [9]. In this study, NAFLD was found to be associated with an increased risk of breast cancer with an OR=1.369 (95% CI 1047-1971, p=0.022), while the elaborated scoring system showed for patients in the category at high risk (therefore having NAFLD, non-alcoholic fatty pancreas disease and elevated uric acid) an OR=3.185 (95% CI 2.145–4.728, p<0.001). Despite the many limitations related to this study, it clearly highlights the close relationship between NAFLD, metabolic syndrome and breast cancer.

In conclusion, it is clear that NAFLD and extrahepatic malignancies are closely related to each other, since they share many common risk factors and, moreover, they can influence each other. Alongside the usual prevention strategies, therefore, it would be desirable to identify the risk of neoplasms among patients with NAFLD, in order to intensify monitoring and obtain, when possible, an early diagnosis and improvement of clinical outcomes in these patients.


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