Researchers at UCLA's Jonsson Comprehensive Cancer Center (JCCC) have found the first direct link between obesity and cancer of the pancreas.

Pancreatic cancer is one of the most deadly forms in humans. Like other cancers, early diagnosis improves long-term survival rates, but this particularly aggressive form does not usually display any early warning signs.

According to the National Cancer Institute, pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, is the fourth leading cancer killer in the US.

The JCCC study states that the overall 5-year survival rates are just 3-5%, with an average survival rate after diagnosis of only 4-6 months.

Current treatment options are limited in both number and effectiveness, so research is concentrating on prevention strategies to make headway before the disease reaches an advanced stage.

Scientists know that lesions called pancreatic intraepithelial neoplasias (PanINs) are precursors to pancreatic cancer and can be treated as markers, even at a precancerous stage. Unfortunately, these are microscopic, and only detectable by biopsy.

Mice and men

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Mice eating a high-fat, high-calorie diet developed more pancreatic intraepithelial neoplasias lesions than mice eating a healthier diet.

The JCCC study, led by Dr. Guido Eibl, JCCC member and professor-in-residence in the department of surgery at David Geffen School of Medicine, revealed that mice made obese with high-calorie, high-fat diets developed abnormally high numbers of these lesions.

This is the first study to show a direct causal link in an animal model between obesity and risk of this deadly cancer.

Obesity in these mice resembles several important clinical features of human obesity, such as weight gain and disturbance of metabolism. Therefore, this mouse model was ideal for unraveling any underlying biological mechanisms of pancreas cancer that are put in motion by obesity.

The study set out to develop diet-induced obesity and development of pancreas cancer in one set of mice and then compare them with a control group of genetically identical mice that was not given a high-fat, high-calorie diet.

Weight gain and lesions

The mice eating the normal diet gained an average of approximately 7.2 g over 14 months. Mice on the high-fat, high-calorie diet more than doubled this with an average weight gain of 15.9 g.

Pathological tests showed that mice fed the normal diet had mostly normal pancreases with very few scattered PanIN lesions.

On the other hand, mice fed the high-fat, high-calorie diet had significantly more PanIN lesions and fewer overall healthy pancreases.

The study showed that the mice fed a diet high in fats and calories gained significantly more weight, had abnormalities of their metabolism and increased insulin levels, and had marked pancreatic tissue inflammation and development of PanIN lesions.

These observations suggest that such a diet leads to weight gain, metabolism disturbances, pancreas inflammation and pancreas lesions that are precursors to cancer.

Dr. Eibl explains:

"The development of these lesions in mice is very similar to what happens in humans. These lesions take a long time to develop into cancer, so there is enough time for cancer preventive strategies, such as changing to a lower fat, lower calorie diet, to have a positive effect."

This research was supported by the National Institutes of Health, the US Department of Veterans Affairs and the Hirshberg Foundation for Pancreatic Cancer Research.