Biography

Dr. Stolzenberg-Solomon received a BS in Nutrition and Dietetics at the University of California, Davis in 1984, followed by a dietetic internship and M.Ed. in Health Science (Nutrition) Education at Vanderbilt University Medical Center and George Peabody School of Education, respectively. After this training she worked as a Registered Dietitian for 10 years. In 1994 she completed a M.P.H. with concentrations in Epidemiology and Nutrition at the Johns Hopkins School of Hygiene and Public Health. Dr. Stolzenberg-Solomon joined the NCI in 1996 as a pre-doctoral fellow in the Cancer Prevention Studies Branch in the Division of Cancer Prevention and Control and subsequently earned a Ph.D, in Epidemiology from the Johns Hopkins Bloomberg School of Public Health in 1999. As a Cancer Prevention Fellow, she continued post-doctoral research at the Cancer Prevention Studies Branch and later Nutritional Epidemiology Branch where she became an Investigator in 2002.

Research Interests

• Dietary, lifestyle, and other risk factors for pancreatic cancer
• One carbon metabolism and cancer

Pancreatic cancer

Pancreatic cancer is estimated to be the 5th most common cause of cancer mortality in the United States. Presently there is no effective manner to screen for the malignancy and the cancer is most often diagnosed at advanced stages which contribute to its rapidly fatal course, with a 5-year survival of < 4%. Few consistent risk factors for pancreatic cancer have been identified, with age and cigarette smoke being the most consistent. An additional 10-15% of pancreatic cancers may be accounted for by inherited germ line disorders. Thirty to 50% of pancreatic cancer may be attributed to dietary factors, although the specific dietary components and mechanisms remain unclear, primarily because of limited and inconsistent study findings. The majority of studies examining diet and pancreatic cancer have used the case-control method, with retrospective ascertainment of diet; for this cancer site in particular, retrospective ascertainment of diet may be fraught with biases and can result in inaccurate risk estimates. Cohort studies with collection of exposure data preceding cancer diagnosis, are less prone to these biases. We have been and plan to continue to explore associations between dietary exposures and pancreatic cancer in prospective cohort studies using questionnaire data, as well as, biomarkers that may shed light on biologic mechanism.

Most of our studies examining exposures and pancreatic cancer have been conducted in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention cohort of 29,133 male Finnish smokers aged 50-69 years at baseline (1985-1988). This cohort is unique because it has high quality dietary data, biospecimens (serum and DNA), as well as > 15 years of follow-up. We have observed significant protective associations for pancreatic cancer with greater dietary folate and serum folate and vitamin B6 (PLP) concentrations and occupational and leisure physical activity greater than sedentary levels and significant positive associations for pancreatic cancer with Helicobacter pylori and CagA strain seropositivity; dietary fat, particularly saturated fat from cream and butter; cigarette smoking; self-reported history of diabetes mellitus and bronchial asthma; and greater tooth loss (endentulous). We have observed null associations for alcohol intake; other dietary factors; body mass index; other self-reported illnesses (e.g. peptic ulcers, heart disease, pancreatitis, allergies); clinical measures of blood pressure and lipids; and insulin like growth factor (IGF)-1 and IGF binding protein-3 concentrations.

In the future we plan to investigate factors and build upon findings that we previously studied in the ATBC cohort, in non-smoking cohorts such as the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the NCI-American Association for Retired Persons (AARP) Diet and Health Study cohorts in order to attempt to replicate and to increase the generalizability of our previous findings. We plan to examine additional dietary and biomarkers as predictors of pancreatic cancer in these cohorts as well. In particular with the growing obesity epidemic in the United States, and as several prospective studies in non-smoking populations have observed associations between obesity, lack of physical activity and pancreatic cancer, we will prioritize investigating these exposures, as well as biomarkers that may clarify potential mechanisms that may explain these associations. Finally, we plan to actively participate in the Harvard Pooling Project and the Cohort Consortium pancreatic cancer working groups that pool data and resources from a number of cohorts in order to increase the power of studies. The Cohort Consortium pancreatic cancer working group plans to study the main effects of genetic polymorphisms and the interactive effects of gene and environmental exposure. As little is known about the etiology of pancreatic cancer, identifying potentially modifiable factors may reduce the burden of this highly fatal disease and have important public health implications.

One carbon metabolism

Over the past two decades evidence has been mounting for folate being an important nutrient in the prevention of cancer. Methyl-deplete diet and status, in particular, low folate intake and status has been positively associated with a number of cancers, including that colorectal, esophageal, breast, stomach, and cervical with colorectal cancer being the most extensively studied. Low folate in combination with low methionine and high alcohol intake, as well as low vitamin B12 and B6 and cigarette smoking are factors that may contribute to a methyl-deplete status. In addition, polymorphisms in genes involved in folate and one carbon metabolism have been associated with cancer particularly colorectal cancer. Inadequate availability of nutrients involved in one-carbon metabolism may contribute to carcinogenesis via imbalances in the methylation and uracil incorporation in DNA that may manifest as aberrant gene expression and diminished chromosomal integrity. We plan to expand the present research in this area by prospectively assessing associations between one-carbon metabolism and cancer in cohort studies using dietary intake data, biomarkers that reflect nutritional status and molecular mechanism, and polymorphisms in critical genes involved in the one carbon pathway.

We have observed protective associations for pancreatic cancer with greater dietary folate intake and serum folate and vitamin B6 in cohort and nested case-control studies conducted in the ATBC Cancer Prevention cohort of male Finnish smokers. The fact that large proportion of our smoker population had marginal folate and B6 status is likely relevant to our study findings. In a case-cohort study conducted in population in Linxian, China, we observed significant positive associations between polymorphisms in two genes that code for enzymes that require folate and B12 as cofactors (methionine synthase reductase, MTRR A66G and methylenetetrahydrofolate reductase, MTHFR C677T and A1298C) and esophageal and gastric cardia cancer. Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world and its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B12. Our results support the hypothesis that folate and vitamin B12, cofactors for their respective enzyme products, may play a role in the carcinogenesis of these cancers.

As the biochemical pathways for the pathways by which one carbon metabolism may contribute to cancer, namely DNA methylation and synthesis, are complex, investigating nutritional and molecular biomarkers of the components in these pathways may be useful in understanding disease mechanisms in epidemiologic studies. Therefore, we are examining the correlation between conventional and integrative nutritional and molecular biomarkers of one carbon nutrient status to determine which markers may be of functional relevance for use in larger epidemiologic cancer studies. We are also evaluating how one carbon related polymorphisms and haplotypes are associated with these biomarkers.

Resources for which we have additional studies ongoing or being planned include the ATBC Cancer Prevention Cohort, Polyp Prevention Trial (PPT), CONCeRN (Colorectal Neoplasia screening with Colonoscopy in asymptomatic, average risk women at Regional Navy/Army centers), and PLCO (breast cancer).

Collaborators

DCEG Collaborators

• Demetrius Albanes, M.D.; Richard Hayes, D.D.S., Ph.D., M.P.H.; Robert Hoover, M.D., Sc.D.; James Lacey, Ph.D.; Michael Leitzman, M.D., Ph.D.; Steven Mark, M.D., Ph.D.; Nathaniel Rothman, M.D. M.P.H., M.S.; Catherine Schairer, Ph.D.; Arthur Schatzkin, M.D. Dr.P.H.; Rashmi Sinha, Ph.D.; Regina Ziegler, Ph.D.

Other NCI Collaborators

• Christian Abnet, Ph.D., M.P.H.; Sandy Dawsey, M.D.; Elaine Lanza, Ph.D.; Linda Nebeling, Ph.D., R.D.; Philip Taylor, M.D., Sc.D.; Joseph Tangrea, Ph.D.; Karen Woodson, Ph.D., M.P.H.

Other Scientific Collaborators

• Larry Appel, M.D., M.P.H.; Thomas Erlinger, M.D., M.P.H., Johns Hopkins University Medical School, Baltimore MD
• Andrew Flood, Ph.D., University of Minnesota, Minneapolis, MN
• Pirjo Pietinen, Ph.D.; Jarmo Virtamo, M.D., National Public Health Institute, Helsinki, Finland
• Martin Blaser, M.D., New York University Medical Center, NYC, NY
• Paul Limburg, M.D., M.P.H., Mayo Clinic, Rochester, MN
• Joel Mason, M.D.; Jacob Selhub, Ph.D., Tufts University School of Medicine, Boston, MA
• Michael Pollak, M.D., Ph.D., McGill University, Montreal, Canada
• Lionel Poirier, Ph.D., NTCR, FDZ, Jefferson, AR
• Clifford Rosen, MECORE Laboratory, St. Joseph Hospital, Bangor, ME
• Stephanie Smith-Warner, Ph.D.; Harvard School of Public Health, Boston, MA