Michael B. Cook, Ph.D.
|Organization:||National Cancer InstituteDivision of Cancer Epidemiology & Genetics, Nutritional Epidemiology Branch|
|Address:||9609 Medical Center Drive Room 7E106|
Dr. Michael Blaise Cook earned his B.Sc. in Genetics at the University of Nottingham, England, and, subsequently, a Ph.D. in Epidemiology at the University of Leeds, England. The focus of his doctoral thesis was sex differences in Barrett’s esophagus and esophageal adenocarcinoma, themes still relevant to his current research portfolio in the Hormonal and Reproductive Epidemiology Branch (HREB). Dr. Cook joined the HREB as a Visiting Postdoctoral Fellow in 2007 before becoming a Research Fellow in 2008 and then an Investigator in 2011. He was awarded the Division of Cancer Epidemiology and Genetics (DCEG) Fellowship Achievement Award for research excellence in 2008, the Director’s Intramural Innovation Award in 2008, and the DCEG Molecular Epidemiology Course Award for novel research proposals. He is an affiliate member of the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) and a Steering Group Committee member of the Asian Barrett’s esophagus Consortium (ABC). Dr. Cook is a strong proponent of high-quality mentorship and he recently completed the NCI Executive Coaching program.
Dr. Cook is interested in the epidemiology of esophageal adenocarcinoma and the precursor metaplasia, Barrett’s esophagus. In addition, he is interested in the etiology of genitourinary neoplasms (testicular and prostate) and sex differences in cancer pathogenesis.
Esophageal adenocarcinoma is a highly fatal cancer—in the United States the five-year survival rate is 19%. Esophageal adenocarcinoma is considered to represent the end of a continuum of disease which initiates with severe gastroesophageal reflux, causing erosion of the native squamous stratified epithelium of the esophagus which may subsequently be re-epithelialized with an intestinal metaplasia containing goblet cells. This metaplasia is known as Barrett’s esophagus and increases the risk of esophageal adenocarcinoma by 10-55 times that of the general population. To elucidate the etiology of these distinct stages of esophageal carcinogenesis, Dr. Cook has conducted analyses of risk factors in the BEACON consortium. The large size of this population allows for novel analyses with high statistical power (e.g., stratifications, tests for interaction, restricted cubic splines). Specifically, he has been involved in assessment of cigarette smoking, alcohol consumption, anthropometric variables, non-steroidal anti-inflammatory drugs, gastroesophageal reflux and anti-reflux medications in relation to Barrett’s esophagus, esophageal adenocarcinoma and, the related neoplasm, esophagogastric junctional adenocarcinoma. These data are helping Dr. Cook shape novel hypotheses, particularly with regards to the effects of obesity on esophageal adenocarcinoma and how this may differ with respect to sex.
The poor survival of esophageal adenocarcinoma patients is partly due to the late stage at which this malignancy most often presents, thus cancer prevention focused on Barrett’s esophagus are important. However, it is uncertain whether risk factors for Barrett’s esophagus can be compared with risk factors for esophageal adenocarcinoma, given that the absolute risk of malignancy remains low (0.5% per year or 1 in 200 patient years) in individuals diagnosed with this metaplastic lesion. Dr. Cook is designing research strategies to address such questions. Adding to the complexity is the evidence that many individuals with Barrett’s esophagus in the general population remain undiagnosed. This may explain why ~90% of esophageal adenocarcinomas are diagnosed on index endoscopy. Thus, noninvasive biomarkers to identify and risk stratify Barrett’s esophagus patients are needed.
Testicular cancer is a rare malignancy which has been increasing in incidence in countries with predominant Caucasian ethnicity. Much of the available evidence suggests that testicular cancer is the result of a developmental abnormality as opposed to the classic carcinogenic paradigm of an accumulation of mutations that disrupt normal cell cycle regulation and apoptosis. Risk factors consistently associated with testicular cancer include cryptorchidism, family history of testicular cancer, and previous diagnosis of testicular cancer. Overall, however, its etiopathogenesis is poorly understood, partly due to its rarity; many studies of this malignancy are small. In an attempt to aid our understanding, Dr. Cook has worked with Dr. Katherine McGlynn (HREB, DCEG) on the US Servicemen's Testicular Tumor, Environmental and Endocrine Determinants (STEED) Study, one of the largest studies of testicular cancer in the world with over 750 cancer cases and 900 controls. Dr. Cook has focused on the early developmental period in relation to testicular cancer. Specifically, he has conducted analyses of childhood physical activity and perinatal exposures. To augment these analyses, Dr. Cook conducted a comprehensive systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk in which he found evidence for associations of height, inguinal hernia, twinning, maternal bleeding during pregnancy, birth order, and sibship size in relation to cancer risk. Ongoing research, promoted by these methodical synopses, includes testing hypotheses of infectious and hormonal mechanisms in the pathogenesis of testicular cancer.
Drawing on his expertise in genetics, Dr. Cook has also been studying the hereditary basis of testicular cancer. Dr. Cook has tested height-related single nucleotide polymorphisms (SNPs) and SNPs located at the 8q24 locus for association with testicular cancer. He is also involved in a genome-wide association study of this malignancy. In addition, Dr. Cook is seeking to elucidate epigenetic hereditary factors in relation to this testicular cancer in a global methylation study that will compare specific histologic types and adjacent normal tissue. Such studies should help shed light on the mechanisms which underlie the natural history of testicular cancer.
Dr. Cook has shown from large descriptive studies that males are much more likely to die from most specific forms of cancer than females and that these disparities are mostly due to sex differences in cancer incidence rather than cancer survival. Thus, more effort is required to understand how risk factors may differ, or be modified, by sex; such a research strategy may offer a novel perspective from which to investigate and elucidate cancer etiology.
Dr. Cook is working within BEACON to investigate sex differences of esophageal adenocarcinoma and Barrett’s esophagus, as the consortium’s sheer size provides a much larger number of women with these lesions than has traditional been studied. In the general population, incidence is approximately 5:1 male to female ratio for this malignancy. In addition, he is involved in the international Male Breast Cancer Pooling Project, developing and optimizing the analytic strategy. Analyses of questionnaire data, DNA, and serum and tissue may help elucidate risk factors for this rare malignancy, and allow comparison with female breast cancer.