Cancer Epidemiology & Prevention

(Click on faculty's name to read about their research)

Dean E. Brenner, M.D.

Dr. Brenner is a clinical oncologist and clinical pharmacologist who played a pivotal role in the development and growth of the Cancer Prevention and Control at the University of Michigan.  Dr. Brenner’s research is focused on the clinical pharmacology of cancer risk reductive interventions (“chemoprevention”), and he has developed new ways to understand pharmacology of natural or synthetic compounds to delay, reverse or prevent the development of invasive cancer.  Therapeutic index, the risk benefit ratio, represents a key barrier in the development and deployment of cancer risk reductive interventions.  Dr. Brenner’s group has focused upon defining the efficacy and toxicity of the polyphenol class of nutritional extracts, curcumin, resveratrol, and gingerols through their action upon the cyclooxygenase and lipoxygenase systems that regular inflammation.  He has developed new ways of identifying and validating biomarkers that may be used for assessment of cancer risk reductive efficacy and early cancer detection.

Dr. Brenner’s work has spanned the spectrum of translational research in cancer prevention.  He serves as principal investigator of a multicenter, international consortium, the Great Lakes/New England Clinical Epidemiology and Validation Center of the Early Detection Research Network (EDRN).  This NCI-funded cooperative network focuses upon the discovery and validation of new surrogate endpoint biomarkers for early diagnosis of carcinogenesis in humans.  A Gastrointestinal Specialized Program of Research Excellence (SPORE) for translation of bench to bedside and back to brench research in pancreatic and colon cancers has been funded with Dr. Brenner as principal investigator.

Dr. Brenner has extensive experience in National peer review activities, having completed a 4 year term on the Cancer Clinical Investigations Review Committee (Subcommittee H), a 4 year term on the FDA’s Oncologics Drug Advisory Committee, and 6 years on the Clinical Oncology Study Section (CONC), 4 years as Chair.  He recently completed a 4 year term on the NIH’s Peer Review Advisory Committee.  He serves as a Senior Editor for Cancer Epidemiology, Biomarkers and Prevention, and is on the Editorial Boards of the Cancer Biomarkers, and Cancer Prevention Research.  Throughout his career, Dr. Brenner has been an effective mentor of more than 20 medical students, graduate students, research fellows, and junior faculty.  He has served as primary or secondary mentor for 6 successfully funded K awards.

Jennifer J. Griggs, M.D., M.P.H.

Research in Dr. Griggs’ program focuses on quality of breast cancer care and quality of patient-provider communication.  Quality of care research addresses in particular disparities in the quality of breast cancer care.  Dr. Griggs has demonstrated that black women with breast cancer are more likely to receive intentionally reduced doses of chemotherapy after surgery.  Women of lower socioeconomic status (SES) are also significantly more likely to receive systematically reduced doses of chemotherapy.  Dr. Griggs and her colleagues have hypothesized that physicians harbor concerns about some patients’ abilities to tolerate full doses of chemotherapy and accordingly reduce doses in an effort to help the patients complete chemotherapy.  Ongoing funded work will address the patient, physician, and health system delivery factors associated with receipt of optimal chemotherapy and the impact of differences in treatment on breast cancer recurrence and survival rates.

Women who are overweight or obese have also been shown to receive intentionally reduced doses of chemotherapy despite evidence that full doses are safe and necessary to achieve the benefits of chemotherapy.  While most obese patients receive full weight-based doses of chemotherapy, Dr. Griggs’ team has demonstrated that up to 40% of obese women receive substantially reduced doses of chemotherapy.  They have also demonstrated that there are wide variations between physicians and between geographic regions in the use of reduced versus weight based doses.  Such variation reflects uncertainty about optimal dosing in obese patients despite the use of full weight-based doses in clinical trials over the last two decades.  Efforts to disseminate information about best chemotherapy dosing practices are the focus of additional research activities.

Additional quality of care research focuses on interlaboratory variation in the quality of key pathology variables—estrogen receptors and HER2 testing in primary breast tumors.  Reassessing these variables in archival specimens at a central laboratory will identify the extent to which there are problems in the quality of assessment of these key variables in population-based samples.

Other research in this program focuses on medical reassurance in patients with ductal carcinoma and on information and other support needs in women who have completed treatment for breast cancer.  Dr. Griggs has demonstrated that women with ductal carcinoma in situ who are told they have a “good cancer” or a “favorable cancer” have higher concerns about recurrence than women who are not; no such impact of this method of reassurance was seen in women with invasive breast cancer.  Ongoing research will investigate the mechanisms by which reassurance leads to distress and other negative responses.  Collaborating on this research is Sarah Hawley, Ph.D.

In addition, Dr. Griggs and her colleagues have shown that women are highly satisfied with information they receive about treatment of breast cancer but are less satisfied with information about long-term effects of treatment and other survivorship issues.  They are developing interventions to address the needs of people completing multimodality treatment of breast cancer.  Collaborators on this project include Nancy Janz, Ph.D., Lawrence An, M.D., M.P.H., James Hayman, M.D., M.B.A., Kathleen Diehl, M.D., and Lynn Henry, M.D., Ph.D.

Dr. Griggs is a member of CanSORT (www.CanSORT.org), a multidisciplinary group of NIH-funded investigators based at the University of Michigan and the Ann Arbor VA Center for Clinical Management Research representing the fields of internal medicine, surgery, radiation, oncology, nursing, behavioral science, health services research, biostatistics, and epidemiology.  CanSORT investigators are located at five universities and cancer centers throughout the United States.  CanSORT studies the quality of cancer care across the continuum of care from prevention to survivorship.  The team also develops and evaluates interventions to improve cancer care including decision tools for patients and clinicians and dissemination strategies to more quickly move research results to the provider community.

Christopher D. Lao, M.D., M.P.H.
Dr. Lao’s research focus has been on establishing a novel human model for early phase interventions in which to test putative prevention agents and to explore critical biomarkers of melanoma carcinogenesis.  The outcome for individuals with advanced or metastatic melanoma is extremely poor due to its inherent resistant to chemotherapy and radiation.  Unfortunately, attempts at melanoma prevention by limiting or blocking sun exposure have not had a significant impact on the incidence and mortality of melanoma in this country.  Chemoprevention represents an innovative approach to combat this deadly cancer by inhibiting or reversing the malignant transformation of a melanocyte or by interfering in the growth, survival or invasion of a transformed cell.  Working with the Cancer Prevention Program and the Multidisciplinary Melanoma Clinic, Dr. Lao is developing a human model that includes patients with a history of melanoma and dysplastic nevi to determine if pharmacologic interventions can modulate critical biomarkers of carcinogenesis as a surrogate for melanoma prevention.  Two biomarkers, nuclear factor kappa B (NF-kappa B) and 12-lipoxygenase (12-LOX) are being analyzed within this model.  The Prevention Group has previously demonstrated that 12-lipoxygenase (12-LOX) over-expression occurs as part of the transition from either a common or dysplastic nevus to melanoma.  Others have shown that ultraviolet radiation and oxidative stress can increase NF-kappa B binding activity in metastatic melanoma cell lines and melanocytes and that apoptosis can be induced through inhibition of NF-kappa B activation.  This suggests that NF-kappa B activation participates in tissue invasion and metastasis, but might also represent an early event in melanoma carcinogenesis that can be targeted.  Dr. Lao is examining the potential of curcumin, the major yellow pigment extracted from turmeric, as a topical chemopreventive agent within this model.  Curcumin has a broad spectrum of activity including down-regulation of cell survival mechanisms in human cancer cells in association with near complete suppression of NF-kappa B binding activity.  Topical application of curcumin has also inhibited TPA-induced tumor formation in animals that paralleled the inhibitory effects on LOX and COX activities.  Dr. Lao has been examining the optimal topical formulation of curcumin using Franz diffusion cells and developing improved HPLC methods for measuring curcumin within this system.  A phase I trial of topical curcumin has been initiated and will be run over the upcoming year.