Overweight Children at Higher Risk for Liver Cancer as Adults

Daniel M. Keller, PhD

May 28, 2012

May 28, 2012 (Lyon, France) — Childhood body mass index (BMI) is positively associated with the risk for primary hepatocellular carcinoma (HCC) in adulthood. This association holds for both boys and girls, increases slightly with age, is consistent across birth years, and is unchanged when other known causes of liver cancer are excluded, Jennifer Baker, PhD, from the Institute of Preventive Medicine at Copenhagen University Hospital, Denmark, reported here at the 19th European Congress on Obesity (ECO).

Paralleling the worldwide epidemic in childhood obesity is an increase in nonalcoholic fatty liver disease (NAFLD), which has now become the most common liver disease in children and which is an early step in the progression of changes in the liver that can lead to liver cancer. Dr. Baker and colleagues therefore investigated whether excess weight from ages 7 to 13 years is associated with liver cancer, and in particular, with HCC, in adults.

They used the Copenhagen School Health Records Register for 326,423 boys and girls born between 1930 and 1989 and correlated the records with cases of liver cancer in the Danish Cancer Registry. BMI z-scores were calculated from internal age- and sex-specific references and were based on heights and weights recorded by school doctors and nurses.

The median age at study entry was 18.0 years (range, 18.0 - 35.2 years); at study exit, it was approximately 55 years (range, 23.1 - 74 years). Using individuals' personal identification numbers, the researchers detected 392 cases of liver cancer during follow up according to International Classification of Diseases (ICD) codes.

There were approximately 280 cases of liver cancer in the men, of which about 200 were HCC. About 110 cases of liver cancer were diagnosed in the women, of which about 70 were HCC.

The risks for adult liver cancer increased slightly with age, "but overall they were quite consistent from 7 to 13 years of age, ranging from about a 12% to about a 20% increased risk," Dr. Baker reported.

The hazard ratio (adjusted for year of birth) for liver cancer in adulthood was 1.14 (95% confidence interval [CI], 1.02 - 1.29) per 1-unit increase in BMI z-score at age 7 years and 1.24 (95% CI, 1.10 - 1.39) per 1-unit increase at age 13 years, with similar risks for boys and girls. The risks specifically of HCC followed a similar pattern.

Risks "were consistent across year of birth, and that's a very interesting finding, because it means a high BMI in a child born in the 1930s actually has the same meaning for an increased risk of cancer in adulthood as a high BMI for a child who [was born] at a later time period," Dr. Baker noted.

About 29,000 individuals were found to have hepatitis B or C, biliary cirrhosis, or alcoholic conditions, which are factors known to increase the risk for liver cancer. When the researchers censored those individuals whose conditions appeared before a diagnosis of liver cancer, the results were essentially unchanged. "It adds credence to the idea that it is childhood BMI that underlies the association [with HCC] and not these other conditions," she said.

Dr. Baker speculated that the association of HCC with childhood BMI may be mediated by its association with adult BMI or its association with various stages of NAFLD and diabetes. She said her group is going back to the data to see how diabetes, NAFLD staging, and adult BMI may affect the findings.

But whatever mechanism underlies the association between childhood BMI and the risk for primary liver cancer, "these results really suggest that the roots of liver cancer should be searched for already in childhood," Dr. Baker said. Beyond the immediate health consequences in childhood, she said the epidemic of childhood overweight may result in poor health outcomes in adulthood, including liver cancer.

Session moderator Berit Heitmann, PhD, professor of nutritional epidemiology and director of the Institute of Preventive Medicine at Copenhagen University Hospitals, Denmark, commented to Medscape Medical News, "It's quite intriguing to me and quite potentially very powerful findings in the sense...that something in your childhood related to obesity can have effects 50 years ahead.... Really we need to look for determinants of lifestyle diseases that we get at the age of 70 or 80 very early in life, at least in addition to other factors."

But Dr. Heitmann added that "there are actually a third or a fourth of the obese people who are metabolically normal...so that some of the children that had a metabolic [dysfunction] in that age, [it] may disappear because of genetics later on, or it may be reinforced despite efforts, and this is an area that we know very little about."

One limitation of the study is that there was no way to show that the overweight children actually had NAFLD, which would have required liver biopsies early on.

Dr. Baker has disclosed no relevant financial relationships. Dr. Heitmann is the director of the institute at which the work was performed, but she was not involved in the study.

19th European Congress on Obesity (ECO). Abstract 131. Presented May 10, 2012.

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