Lindsay Morton: Making the Most of Consortia

In almost all of her research, Lindsay M. Morton, Ph.D., a tenure-track investigator in DCEG’s Radiation Epidemiology Branch (REB), has used either formal consortia or extensive networks of scientific collaborators in the search for clues to the causes of cancer. Since her early graduate work, Dr. Morton has focused her research on areas of cancer epidemiology that require large numbers of subjects: rare outcomes, histologic subtypes, and gene-environment interactions. “I’ve been fortunate to work with some truly dedicated and talented collaborators,” Dr. Morton said. “By working together, we have been able to accomplish bigger and better science.”

Investigating Lymphoma Subtype Etiology in the InterLymph Consortium

As a graduate student at Yale University, Dr. Morton initially was interested in the role of the immune system in the development of cancer. She soon shifted her focus to non-Hodgkin lymphoma (NHL) and, specifically, how etiologic heterogeneity among lymphoma subtypes might inform the search for elusive risk factors for this complex disease. To do this, Dr. Morton pooled data from a Yale case-control study of NHL with two other studies—including the NCI/SEER (Surveillance, Epidemiology and End Results) NHL Study—in order to amass the number of cases necessary to power an investigation of risk by subtype. The project quickly expanded to include an additional 10 studies (CEBP 2005¹, Lancet Oncol 2005²), becoming the first pooled analysis in the then-new InterLymph Consortium.

After joining NCI, one of Dr. Morton’s major efforts was to conduct a comprehensive evaluation of NHL subtypes and a broad range of putative risk factors, including medical history, lifestyle, and family history (Blood 2008³). She has further expanded this research as the leader of the InterLymph NHL Subtypes Project, a consortium-wide initiative involving 20 studies and information on 11 NHL subtypes, the most comprehensive analysis of NHL etiology to date.

Moving Closer to the Clinic: Studying Second Cancer Risk Factors

Dr. Morton’s experience fostering interdisciplinary collaborations for NHL has prepared her for the successful management of similar teams working on second cancers, a field to which she is particularly suited given her expertise in lymphatic and hematopoietic malignancies. Lymphoma and leukemia survivors are at increased risk of developing a second malignancy, and, likewise, survivors of certain other cancers are at increased risk of developing lymphoma and leukemia. Although they are a leading cause of morbidity and mortality among cancer survivors, second cancers are still rare events in absolute terms, so consortia and large-scale studies are necessary for meaningful research.  

“New treatments for cancer have dramatically improved survival. Unfortunately, too many cancer survivors experience a second malignancy,” Dr. Morton said. “By learning more about how treatments, cancer risk factors, and genetic susceptibility contribute to second cancer risk, we hope to provide an evidence base for follow-up care and benefit public health by improving outcomes for the long term.”

Dr. Morton leads a large, international, multi-center study of second cancers of the gastrointestinal (GI) tract among patients who received radiotherapy. Initial findings have demonstrated increased risk of esophageal cancer with increasing radiation dose to the esophagus following breast cancer radiotherapy (Ann Oncol 2012⁴) and increased risk of stomach cancer with increasing radiation dose to the stomach following cervical cancer radiotherapy (Int J Radiat Oncol Biol Phys 2013⁵). Future analyses will explore possible joint effects of chemotherapy and radiation on risks for second GI cancers.

Historically, second cancer research has focused on treatment-related effects, but there is increasing recognition that lifestyle and host factors, especially genetics, also may be important. Dr. Morton is working to create an infrastructure to address this broader set of risk factors within SEER-Medicare, the NCI Cohort Consortium, the Childhood Cancer Survivor Study (CCSS), and studies of individuals with cancer predisposition syndromes.

Childhood cancer survivors are particularly vulnerable to second cancers because of the many years of life ahead of them during which a new malignancy could develop. To explore risk within this special population, Dr. Morton is collaborating with investigators of the CCSS to conduct a genome-wide association study. The goal is not only to expand our understanding of genetic susceptibility to second cancers but also to elucidate the relationship between genes and radiation- and chemotherapy-related carcinogenesis. In a separate study of retinoblastoma (RB) survivors, Dr. Morton is investigating the role of specific RB1 mutations in second cancer risk and using exome sequencing to identify potential modifiers of the gene. “Our goal is to determine whether certain individuals are more susceptible to treatment-related second cancers, which ultimately could impact patients’ treatment choices,” Dr. Morton said.

Scientific Mentoring: Paying It Forward

Fundamental to her approach to this research is an emphasis on training the next generation of epidemiologists. Mentoring is an integral part of Dr. Morton’s work. She remarked, “The best way to thank the people who have mentored me is to pass it on.”

Reference

1. Morton LM et al. Cigarette smoking and risk of non-Hodgkin lymphoma: A pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). Cancer Epidemiol Biomarkers Prev 2005 Apr.
2. Morton LM et al. Alcohol consumption and risk of non-Hodgkin lymphoma: A pooled analysis. Lancet Oncol 2005 Jul.
3. Morton LM et al. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. Blood 2008 Dec 15; Epub 2008 Sep 16.
4. Morton LM et al. Risk of treatment-related esophageal cancer among breast cancer survivors. Ann Oncol 2012 Dec; Epub 2012 Jun 27.
5. Kleinerman RA et al. Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer. Int J Radiat Oncol Biol Phys 2013 Aug; Epub 2013 May.