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.
Something that has an
effect outside the liver, for example when viral hepatitis affects the kidneys
or causes depression.
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
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
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.