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Doherty Group Research

Using molecular epidemiology to leverage bioinformatic approachestowards better understanding cancer.

Biomarkers to improve lung cancer screening

Lung cancer is responsible for more deaths than prostate, breast and colon cancers combined. While smoking cessation is a key means to reduce the incidence of lung cancer, former smokers remain at high risk for many years after quitting. Low dose CT scan screening of high-risk individuals holds promise to reduce lung cancer mortality, but the false positive rate even among this high-risk group remains quite high. My work focuses on identifying factors that differentiate between individuals with a heavy smoking history who will, and who will not, eventually develop lung cancer, with the goal of incorporating these factors into models for risk stratification for lung cancer screening regimens, and reducing false positives.

Telomere length, genetic variation in telomere length, and cancer risk

Telomeres cap chromosome ends and protect cells from genomic instability, and shorten with age, cigarette smoking, oxidative stress, and inflammation. Peripheral blood telomere length has been associated with numerous cancer types, and the region encoding the telomerase gene, TERT, contains susceptibility loci for many different cancers. My study of global and chromosome arm-specific telomere length measured prior to diagnosis, variation in telomere structure and maintenance genes, and lung cancer risk and survival (R01 CA151989, PI JA Doherty) in heavy smokers is by far the largest prospective study to date, and the only study to examine chromosome arm specific telomere length as well as relationships with survival.

Characterizing molecular subtypes of ovarian cancer across populations

Ovarian cancer is challenging to study for a number of reasons. It is a rare disease and therefore screening tests require nearly perfect sensitivity and specificity to be effective, and it is typically diagnosed at a late stage, with poor survival. Also, accumulating evidence has led to the understanding that ovarian cancer is not a single disease; rather, it is thought that the various ovarian cancer histologic types and high grade serous (HGSC) molecular subtypes may have different etiologies. Furthermore, almost all research of the molecular epidemiology of ovarian cancer to date has been in Caucasian women. Therefore, my ovarian cancer research program concentrates on three main areas: 1. To elucidate similarities and differences in epidemiologic and genetic risk factors and survival across the histologies and HGSC subtypes of ovarian cancer, with the goal of understanding the underlying causes of each so that preventive measures can be developed; 2. To identify candidate genes and pathways that drive the development of each of the subtypes so that targeted treatments can be developed; and 3. To characterize epidemiologic and molecular features of ovarian cancer in diverse populations to aid in developing regionally appropriate care.


I collaborate extensively with a large number of ovarian cancer researchers through the international Ovarian Cancer Epidemiology Consortium (OCAC), the Ovarian Tumor Tissue Analysis (OTTA) consortium, and the Ovarian Cancer in Women of African Ancestry Consortium (OCWAA), and with lung cancer researchers through the International Lung Cancer Consortium (ILCCO). As well, I have numerous collaborations through the NCI-sponsored Genetic Association Mechanisms in Oncology (GAME-ON) Follow-up of Ovarian Cancer Genetic Association and Interaction Studies.