According to a cohort study published online October 21 in the Journal of the National Cancer Institute, risk factors for hepatocellular carcinoma (HCC),such as obesity, smoking, high alcohol consumption, and chronic hepatitis B and C infection, contribute to a large percentage of the disease in Europe.

Although it has been know for a few decades that there is a connection between liver cancer and hepatitis B and C, alcohol consumption, smoking, and obesity are common risk factors, and even though they represent a lower relative risks, they also contribute to the development of HCC. Researchers discovered that there were many more individuals in Europe with HCC who smoked than individuals infected with hepatitis. Earlier research has not evaluated the contribution of each individual risk factor.

In order to find out how each of these risk factors contributed to liver cancer, Dimitrios Trichopoulos, Ph.D., of the Harvard School of Public Health, and his team used data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which was created in order to study the role of biological, dietary, environmental and lifestyle factors in the etiology of cancer and other diseases in several countries across Europe. The investigators compared 115 individuals with HCC to 229 control subjects.

In the cohort, they discovered that 47.6% of HCC cases were linked to smoking, 20.9% were linked with hepatitis C, 13.2% with hepatitis B, 16.4% with obesity, and 10.2% with heavy alcohol consumption.

The researchers explain:

“We have shown that hepatocellular carcinoma, one of the most lethal human cancers, is largely amenable to primary prevention with existing knowledge and technology. Although chronic infection with HBV and/or HCV was the strongest risk factor for hepatocellular carcinoma, tobacco smoking was responsible for more cases of hepatocellular carcinoma than either or both these viruses in the population.”

In an associated report, Morris Sherman, M.D., and Josep M. Llovet, M.D., of the Mount Sinai School of Medicine say that the results from this investigation are consistent with results from other epidemiological investigations, although the numbers need to put into context.

In particular, they warn that smoking should not be given to much importance as a risk factor of HCC, due to the large majority of individuals who smoked in the investigation, making the associated risk significantly higher than it might have been otherwise.

They highlight that to date, no investigations support the belief that smoking is a stand-alone risk factor for the disease. Although, the data on smoking is important.

They explain:

“We should be counseling our patients who have other risk factors for hepatocellular carcinoma to quit smoking. Of course, there are many other health reasons to stop smoking. Here is one more.”

An additional investigation on HCC in this issue of the Journal confirms the connection between hepatitis B and liver cancer among a population cohort in Greenland. However, they discovered that those studied in Greenland have a relatively low prevalence of liver cancer compared to individuals in other parts of the world. This indicates that there is a more benign course of Hepatitis B infection prevalent in Greenland, resulting in a lower rate of liver cancer.

Marlene M. Børresen, M.D., Ph.D., of the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and her team, looked at 8879 individuals from Greenland who participated in a population-based serum survey in 1987 and 1998, who were followed until 2010. The investigators checked all participants for hepatitis B status, and discovered that the rate of liver cancer was much higher for those who tested HBV positive compared to those who tested negative. In addition, they also discovered that the prevalence of HCC was significantly lower in Greenland compared to other areas in the world have had a similarly high prevalence of hepatitis B.

They explain that this discovery could be attributable to numerous factors: for example, that generally the infection is transmitted during adolescence and adulthood, whereas those who were infected during childhood have a higher risk of developing liver cancer; and that the HBV strains that are linked to an increased risk of HCC are less common in Greenland than other places. In addition, they found that low alcohol consumption and low smoking rates may also contribute to the lower rates of HCC, as well as the relatively young age of the participants studied in the cohort (mean age at recruitment was 33.4 years, with follow-up occurring in the mid-fifties.)

In an associated article, Morris Sherman, M.D., and Josep M. Llovet, M.D., of the Mount Sinai School of Medicine agree with the researchers that genotype differences might in part account for the lower prevalence of liver cancer amongst individuals with hepatitis B. According to Sherman and Llovet, in Greenland, the D and B6 genotypes of hepatitis B are most common, and that “the incidence of hepatocellular carcinoma in people infected by genotype B6 has not been documented.” They add that viral load and infection by mutations of hepatitis B are also risk factors of liver cancer that this investigation did not research.

Written by Grace Rattue