Posts Tagged ‘wolpin’

New genetic risk markers in pancreatic cancer

The markers are variations in the inherited DNA code at particular locations along chromosomes. Several of these variations in the DNA code were identified that influence an individual’s risk for pancreatic cancer.

The discovery of these markers — along with four that were previously identified is important for several reasons, said Brian Wolpin, MD, MPH, first author of the report published online by Nature Genetics. One is that further study of these DNA variants may help explain on the molecular level why some people are more or less susceptible to pancreatic cancer than the average person. A second is the potential to identify people at increased risk who then might be candidates to undergo MRI or ultrasound scanning to look for early, treatable pancreatic tumors.

“Currently there is no population screening program for pancreatic cancer, which in 80 percent of cases is discovered when it’s too late to allow curative surgery — the cancer has already spread,” said Wolpin.

The only healthy individuals currently screened for pancreatic cancer are members of high risk families due to multiple family members with pancreatic cancer. “But the field has been struggling to find factors that can identify people at highest risk in the general population, when a strong family history is not present,” Wolpin said.

The study findings represent analyses of DNA from 7,683 patients with pancreatic cancer and 14,397 control patients without this cancer, all of European descent, from the United States, Europe, Canada, and Australia. The scientists used sequencing technology to examine more than 700,000 sites of the genome known to have single nucleotide polymorphisms (SNPs) — differing versions of a single letter of DNA code. These variations can alter the expression of a gene or the content of its message, and the researchers looked for variants that were associated with the risk of having pancreatic cancer. Research of this type is called a genome-wide association study, or GWAS.

Wolpin said the results confirmed the presence of four risk-associated SNPs that had been identified in a previous, smaller GWAS study. In addition, five new risk markers were discovered and a sixth that was of borderline statistical significance.

The risks linked to each SNP or marker were largely independent and additive, so that they may have utility in future attempts to identify individuals in the general population at higher risk for pancreatic cancer. The average lifetime risk of pancreatic cancer is 1.5 percent.

The long-term goal is to create a “risk stratification tool” that could be used in primary care practice to identify individuals who should undergo screening for pancreatic cancer with tests such as ultrasound or MRI.

The report includes authors from around the world, and includes several senior authors, one of whom is Charles Fuchs, MD, MPH, of Dana-Farber.

The project, known as PanScan III, was funded by numerous sources, including the National Cancer Institute of the National Institutes of Health under contract number HHSN261200800001E and the Lustgarten Foundation.

source : http://www.sciencedaily.com/releases/2014/08/140803193131.htm

Long-term obesity associated with poorer pancreatic cancer survival

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Most patients with pancreatic adenocarcinoma, which accounts for more than 90% of new cases, survive less than a year after their diagnosis.

Obesity is a major public health problem in the United States and many other countries around the world. While it is well known that obesity is a risk factor for heart disease and diabetes, it is becoming increasingly clear that it is also associated with cancer risk and outcomes. In fact, scientists predict that obesity will become the leading preventable cause of cancer in the near future.

Several prior studies have shown that elevated BMI increases the risk of developing pancreatic cancer, but thus far there has been little research on whether BMI affects the aggressiveness of the disease or survival after diagnosis.

"This study adds to mounting evidence for the role of weight control in improving outcomes for patients with cancer. It also reinforces the importance of maintaining a healthy weight throughout your life, which may lead to better outcomes after diagnosis and help prevent pancreatic cancer from developing," said senior study author Brian M. Wolpin, MD, MPH, an assistant professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, MA. "While our findings will not affect the way we treat patients today, they provide new leads for investigating the molecular pathways that may be responsible for the survival difference between obese and healthy-weight patients. Hopefully, in the future, that research will bring new approaches for treatment of pancreatic cancer."

Researchers evaluated the association between patients’ BMI in 1986 and survival after diagnosis of pancreatic cancer among participants from two large prospective cohort studies — the Nurses’ Health Study and the Health Professionals Follow-Up Study. Participants of those studies were surveyed on medical history, health behaviors, and lifestyle choices. The present study assessed 902 cases of pancreatic adenocarcinoma that were diagnosed during a 24-year period.

Overall, the median length of survival after diagnosis for those patients was five months. According to Dr. Wolpin, on average, healthy weight patients (BMI less than 25 kg/m2) lived 2 to 3 months longer than obese patients (BMI greater than or equal to 35 kg/m2). The association between higher prediagnostic BMI and shorter survival persisted after adjusting for differences in age, gender, race/ethnicity, smoking status, and disease stage. Obese patients were also more likely to be diagnosed with advanced disease — 72% of obese patients had metastatic disease at diagnosis compared to 59% of healthy-weight patients.

The association between BMI and survival was even stronger among the 202 patients with high BMI assessed 18-20 years before diagnosis. Assuming that most people remain overweight once they gain weight, according to Dr. Wolpin, this finding suggests that being overweight for a prolonged period of time leads to worse outcomes. This study also suggests further avenues of research on the link between obesity and cancer. For example, it is not yet clear if the same changes that promote tumor development in obese people also affect the aggressiveness of the tumor. Several ongoing studies are already exploring metabolic (energy and nutrient processing) pathways and genomic changes in relation to obesity and cancer. This work might reveal whether tumors that develop in obese people are susceptible to different treatments than tumors that develop in healthy-weight people.

source : http://www.sciencedaily.com/releases/2013/10/131021211454.htm