Janet L. Stanford

The role of environmental, lifestyle and genetic factors in cancer etiology, progression and mortality

My main research interests focus on hormonal, environmental, lifestyle and genetic factors that may alter cancer risk, cancer progression, or disease outcomes such as cancer-specific mortality. The role of underlying genetic susceptibility based on rare, inherited and highly penetrant mutations as well as more common genetic variants of lower penetrance is also a major focus of my research. As a cancer epidemiologist, I have been involved in the development, implementation, and analyses of research studies of the etiology and progression of several different types of cancer, however, my primary focus is on prostate cancer.

The completion of two large population-based case-control studies of risk factors for prostate cancer has allowed us to examine environmental/lifestyle exposures and genetic polymorphisms in candidate genes in relation to prostate cancer etiology and outcomes. Selected results from these studies have shown that: 1) vasectomy is not associated with risk of prostate cancer; 2) higher consumption of vegetables and moderate intake of red wine are each associated with reduced risks of prostate cancer; 3) high intensity cigarette smoking increases the risk of prostate cancer; 4) there is an increased risk of prostate cancer among men with a first-degree family history of prostate cancer who carry a specific genetic variant in the CYP17 gene, which is involved in testosterone production; 5) men who are null for the glutathione S-transferase (GST) M1 gene have an increased risk of prostate cancer, particularly among heavy smokers; 6) men who are carriers of BRCA2 mutations have an increased risk of prostate cancer; and 7) genetic variants on chromosome 8q24 are associated with elevated risks of prostate cancer, particularly more aggressive tumors.

We are currently following a large cohort of prostate cancer patients long-term to evaluate how environmental/lifestyle factors and genetic polymorphisms in candidate genes within pathways of interest for prostate cancer may affect disease progression/recurrence and prostate cancer-specific mortality. Results from these studies indicate that: 1) obesity at the time of prostate cancer diagnosis is associated with over a 2-fold excess risk of adverse outcomes (i.e., progression to metastatic cancer, death from prostate cancer); 2) smoking at the time of prostate cancer diagnosis is associated with adverse patient outcomes; and 3) men who are null for the glutathione S-transferase (GST) M1 gene (i.e., they have no copies of the gene) have an excess risk of prostate cancer-specific mortality. Our ongoing studies aim to identify combinations of genetic variants that may be useful, in addition to standard clinical factors, for better prediction of individual patient outcomes. In addition, we are evaluating how the diagnosis and treatment of prostate cancer affect long-term urinary, sexual and bowel function and quality of life.

I am principal investigator for the data collection component of the Prostate Cancer Genetic Research Study (PROGRESS), a large study of high-risk prostate cancer families ascertained from across North America. We have enrolled over 300 families with multiple members who have been diagnosed with prostate cancer, some at particularly early ages. DNA samples, baseline and follow-up questionnaires, and medical records are collected on participants. A genome-wide microsatellite scan and linkage analyses were recently completed and highlighted several regions of interest that we are following up with further studies. We are currently completing a genome-wide dense SNP scan to identify new loci that may harbor prostate cancer susceptibility genes. Over recent years, we reported a significant region of linkage on chromosome 7q in a subset of Jewish prostate cancer families and are working on cloning the responsible gene. We also have identified several regions of interest for more aggressive prostate cancer phenotypes. The long-term goal of PROGRESS is to identify loci that may contain genes with mutations responsible for hereditary prostate cancer, particularly the more clinically significant subtypes.