Non-alcoholic fatty liver disease raises the risk of cancer in overweight people

Obesity without non-alcoholic fatty liver disease (NAFLD) does not raise the risk of cancer, but people with NAFLD who are also obese are almost twice as likely to be diagnosed with cancer as non-obese people of the same age who did not have NAFLD, US researchers report in the Journal of Hepatology.

Excess body weight has been identified as a risk factor for cancer in numerous large epidemiological studies. But the mechanism by which excess weight leads to the development of cancer is unclear, and some studies have shown that different patterns of fat distribution affect cancer risk.

NAFLD develops as a result of metabolic disorders including type 2 diabetes, insulin resistance and elevated lipids, as well as obesity. These conditions lead to the accumulation of fat in the liver. Eventually the build-up of fat may lead to inflammation and scarring of the liver, and in a small minority of people with NAFLD, to the development of liver cancer.

Cancer is one of the most frequent causes of death in people with NAFLD. The study was designed to establish which cancers occur most frequently in people with NAFLD, and the extent to which cancer risk is determined by obesity or NAFLD.

The researchers at the Mayo Clinic, Rochester, Minnesota, used data derived from medical records in Olmsted County, Minnesota. This database captures records on virtually everyone who lives in the county and allowed the researchers to identify all cases of NAFLD diagnosed between 1997 and 2016.

Each case was matched with three individuals of the same age and sex without NAFLD who lived in Olmsted County. The investigators identified 4722 cases of NAFLD, a prevalence of 8%, and 14,441 controls. People diagnosed with NAFLD were more likely to be obese (body mass index of 30 or above) (66% vs 35%), to have type 2 diabetes (95% vs 33%) and to have elevated cholesterol and/or triglycerides (59% vs 33%).

A total of 2224 cancers were diagnosed in the study population during a median follow-up period of eight years. The investigators measured the incidence rate ratio of cancers in the NAFLD population, that is, the ratio of cancers diagnosed in people with NAFLD compared to those without, per 100,000 person-years of follow-up.

Apart from increasing the risk of liver cancer (incidence rate ratio [IRR] 2.8, 95% CI 1.6-5.1), NAFLD was also associated with an increased risk of uterine cancer (IR 2.3, 95% CI 1.4-4.1), stomach cancer (IRR 2.3, 95% CI 1.3-4.1), pancreatic cancer (IR 2.0, 95% CI 1.2-3.3) and colon cancer (IRR 1.8, 95% CI 1.1-2.8).

The risk of developing colon cancer was 90% higher in men with NAFLD compared to women with NAFLD (IRR 1.9, 95% CI 1.3-2.8), but gender had no effect on the risk of other cancers.

NAFLD was also associated with developing several cancers at a younger age. The elevated risk of developing pancreatic cancer, colon cancer and ovarian cancer in people with NAFLD declined with age.

Looking at obesity as a risk factor for cancer, the researchers found that when people with NAFLD were compared to obese people without NAFLD, obesity was not a risk factor for developing cancer. In contrast, people with NAFLD had twice the risk of developing cancer of obese people without NAFLD (IRR 2.0, 95% CI 1.5-2.7).

The investigators say that “it is biologically plausible that NAFLD is a risk factor for cancer, not only of [the] liver, but also of close proximity organs such as the gastrointestinal tract.” In this model of cancer development, fat deposited in the liver might create an inflammatory microenvironment which promotes tumour emergence and growth.

On the other hand, they say, NAFLD might simply be a better predictor of cancer risk because it identifies a form of obesity that is more prone to cancer development, and that body mass index does not discriminate sufficiently between harmless fat and harmful fat deposits.

The investigators say that their results should be used in counselling people with NAFLD about their cancer risk.