Janet L. Stanford
Ph.D., Johns Hopkins University, Epidemiology, 1986.
M.P.H., Emory University, 1982.
B.S., Georgia State University, Nursing, 1980.
The role of environmental, lifestyle and genetic risk factors in relation to cancer etiology, progression and mortality
My main research interests focus on hormonal, environmental, lifestyle and genetic factors that may alter cancer risk, cancer progression, and disease outcomes such as cancer-specific mortality. The role of underlying genetic susceptibility based on rare, and high penetrance mutations as well as more common genetic variants of lower penetrance is 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 current concentration 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 cruciferous vegetables, moderate intake of red wine, and regular aspirin use 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.
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 as well as single nucleotide polymorphisms (SNPs) identified from genome-wide scans 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) patients who are treated with androgen deprivation therapy have different outcomes based on genetic variation in the megalin gene, which is involved in androgen transport. Our ongoing studies aim to identify individual SNPs and 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 general health-related quality of life.
I am principal investigator for the data collection component of the Prostate Cancer Genetic Research Study (PROGRESS), a large family-based study of hereditary prostate cancer. We have enrolled over 300 families with multiple members who have been diagnosed with prostate cancer, some at particularly early ages. Blood samples, baseline and follow-up questionnaires, and medical records are collected on participants. Two genome-wide scans using microsatellite and SNP markers have been completed. Linkage analyses highlighted several regions of interest (e.g., chromosomes 15q, 22q) that we are following up with further studies. We are currently completing a next-generation sequencing project to identify genetic mutation(s) in the 15q linkage region. We are also initiating a whole-exome sequencing project on selected high-risk families with aggressive and/or early onset prostate cancer. The long-term goal of PROGRESS is to identify loci that may contain genes with mutations responsible for hereditary prostate cancer.
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.. Journal of medical genetics.. 2016.
A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.. 2016.
Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.. International journal of cancer. 139(7):1520-1533.. 2016.
Epigenome-wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-lethal Progression in Men with Clinically Localized Prostate Cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research.. 2016.
Blood lipids and prostate cancer: a Mendelian randomization analysis.. Cancer medicine. 5(6):1125-1136.. 2016.
Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.. Journal of the National Cancer Institute. 108(7). 2016.
The Comparative Harms of Open and Robotic Prostatectomy in Population-Based Samples.. The Journal of urology. 195(2):321–329.. 2016.
Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.. American journal of human genetics.. 2016.
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.. Nature communications. 7:10979.. 2016.
Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.. Human molecular genetics. 24(19):5603-5618.. 2015.
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.. Human molecular genetics. 24(19):5589-5602.. 2015.
Genome-wide association study of prostate cancer-specific survival.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 24(11):1796-1800.. 2015.