DNA Methylation Markers and Pancreatic Cancer Risk

Pancreatic cancer is the 4th leading cause of cancer deaths in the US. Due to the lack of early symptoms, pancreatic cancer is difficult to identify at early stages and no screening is available for the general population. Identifying pancreatic cancer at earlier stages could significantly improve survival with increased opportunities for surgery. New high-dimensional arrays designed to measure DNA methylation levels at hundreds of thousands of CpG sites throughout the genome have opened opportunities to examine the role of DNA methylation in cancer risk using blood samples. Using this method, archived samples from prospective studies can be used to examine early changes in the DNA methylation levels in individuals who develop cancer months or years later, providing new opportunities to better understand biological mechanisms and, perhaps, identify biomarkers for early detection. Pancreatic cancer cases and matched controls were obtained from 3 large cohort studies, the Nurses' Health Study (NHS), the Physician's Health Study (PHS), and the Health Professionals Follow-up Study (HPFS), to measure DNA methylation in stored buffy coats using a nested case-control study design.]]>
Pancreatic cancer cases were included if confirmation of the disease was made using medical or death records. Cancer registry data were also used to provide additional pathology data for cases with missing medical records. Only primary adenocarcinoma of the exocrine pancreas were included; those with non-exocrine pancreatic tumors were excluded. All cases had to be diagnosed after the participants provided blood samples (i.e. all were incident cases). Control subjects were matched on cohort (which also matches on sex), age (+/- 1 year), date of blood draw (month 3+/- and year), smoking (never, past, current) and race (White/other).]]>
The NHS was initiated in 1976, when 121,700 female U.S. registered nurses between ages 30 to 55, residing in 11 larger U.S. states completed and returned the initial NHS questionnaire. For this cohort, blood was collected from 32,825 participants in 1989-1991. The HPFS cohort was initiated in 1986, when 51,529 men living in all U.S. states, aged 40 to 75 years completed the initial HPFS questionnaire; 16,000 participants from this cohort provided a blood sample between1993-96. The PHS was a randomized trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in the reduction of cancer incidence. In 1982, 22,071 male physicians, age 40 to 84 years, with no history of cardiovascular disease or cancer, were assigned randomly in a factorial design to receive aspirin (325 mg), beta-carotene (50 mg), or placebo; 14,916 (68%) participants provided baseline blood samples during the run-in period prior to randomization (1982-1983). All blood specimens were drawn by participants and mailed overnight, and upon receipt, the samples were aliquoted and frozen for future analyses.]]>