Janet Stanford, PhD

Janet Stanford, PhD

Full Member, Epidemiology
Public Health Sciences Division

Education

Ph.D., Johns Hopkins University, Epidemiology, 1986.
M.P.H., Emory University, 1982.
B.S.N. Georgia State University, 1980.

Research Focus

The role of environmental, lifestyle and genetic risk factors in relation to prostate cancer etiology, disease progression, and cancer-specific mortality; functional and quality of life outcomes after diagnosis and treatment of prostate cancer; germline genetic and tumor somatic alterations that may be useful as biomarkers for predicting risk or adverse prostate cancer patient outcomes.

My main research interests focus on hormonal, environmental, lifestyle and genetic factors that may alter cancer risk, tumor progression, and disease outcomes such as recurrence-free and cancer-specific survival. The role of underlying genetic susceptibility is a major focus of my research, which has involved studies of both common and rare genetic variants in the general at-risk population and in high-risk families with a pattern of hereditary prostate cancer. As a cancer epidemiologist, I have been involved in the development, implementation, and analyses of data from 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  relation to risk of developing prostate cancer and disease-specific 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) men who are carriers of germline BRCA2 mutations have an increased risk of prostate cancer; and 5) several genetic variants on chromosome 8q24 are associated with elevated risks of prostate cancer. DNA samples and data from these studies have been included in two large collaborative international genetics consortia (COGS, PRACTICAL; ICPCG) for discovery and validation of genetic susceptibility loci for prostate cancer; to date, over 160 SNPs associated with risk of developing prostate cancer have been confirmed through these efforts.

We are following a large population-based cohort of prostate cancer patients long-term to evaluate how environmental/lifestyle factors and genetic polymorphisms may affect disease recurrence/progression and prostate cancer-specific survival. Results from these studies have shown 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-lethal prostate cancer); 2) smoking at the time of prostate cancer diagnosis is associated with adverse patient outcomes; and 3)specific SNPs (e.g., in IL4) are associated with risk of aggressive prostate cancer. Primary prostate tumor tissue obtained at surgery has been used for integrative molecular epidemiology studies based on genome-wide tumor DNA methylation and transcriptome profiles, combined with germline genetic, clinical, and epidemiological data.  Our ongoing studies aim to identify host (e.g., germline genetic variants) and tumor (e.g., DNA methylation, gene expression) alterations that may serve as biomarkers of aggressive prostate cancer and help distinguish patients at diagnosis who are most likely to have life-threatening tumors. Such biomarkers could have clinical utility for better prediction of an individual patient’s prognosis, identifying those men who need closer monitoring, adjuvant therapy, and novel clinical trials aimed at improving patient outcomes. In addition, we have ongoing studies  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 (HPC). We have enrolled over 2,000 members of 307 families in which multiple members 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 (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 recently completed a next-generation sequencing project to identify rare genetic mutation(s) in the 15q linkage region. We have also completed a whole-exome sequencing (WES) project on 75 selected high-risk families with aggressive and/or early onset prostate cancer and identified several novel rare variants associated with HPC; WES is underway for an additional 140 HPC families with the goal of finding additional rare variants that play a role in PCa predisposition. The long-term goal of PROGRESS is to identify genetic mutations responsible for HPC.

Publications

1. Eeles RA, Olama AA, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Ghoussaini M, Luccarini C, Dennis J, Jugurnauth-Little S, Dadaev T, Neal DE, Hamdy FC, Donovan JL, Muir K, Giles GG, Severi G, Wiklund F, Gronberg H, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindstrom S, Kraft P, Hunter DJ, Gapstur S, Chanock SJ, Berndt SI, Albanes D, Andriole G, Schleutker J, Weischer M, Canzian F, Riboli E, Key TJ, Travis RC, Campa D, Ingles SA, John EM, Hayes RB, Pharoah PD, Pashayan N, Khaw KT, Stanford JL, Ostrander EA, Signorello LB, Thibodeau SN, Schaid D, Maier C, Vogel W, Kibel AS, Cybulski C, Lubinski J, Cannon-Albright L, Brenner H, Park JY, Kaneva R, Batra J, Spurdle AB, Clements JA, Teixeira MR, Dicks E, Lee A, Dunning AM, Baynes C, Conroy D, Maranian MJ, Ahmed S, Govindasami K, Guy M, Wilkinson RA, Sawyer EJ, Morgan A, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As NJ, Woodhouse CJ, Thompson A, Dudderidge T, Ogden C, Cooper CS, Lophatananon A, Cox A, Southey MC, Hopper JL, English DR, Aly M, Adolfsson J, Xu J, Zheng SL, Yeager M, Kaaks R, Diver WR, Gaudet MM, Stern MC, Corral R, Joshi AD, Shahabi A, Wahlfors T, Tammela TL, Auvinen A, Virtamo J, Klarskov P, Nordestgaard BG, Røder MA, Nielsen SF, Bojesen SE, Siddiq A, Fitzgerald LM, Kolb S, Kwon EM, Karyadi DM, Blot WJ, Zheng W, Cai Q, McDonnell SK, Rinckleb AE, Drake B, Colditz G, Wokolorczyk D, Stephenson RA, Teerlink C, Muller H, Rothenbacher D, Sellers TA, Lin HY, Slavov C, Mitev V, Lose F, Srinivasan S, Maia S, Paulo P, Lange E, Cooney KA, Antoniou AC, Vincent D, Bacot F, Tessier DC; COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiative; Australian Prostate Cancer Bioresource; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; UK ProtecT (Prostate testing for cancer and Treatment) Study Collaborators; PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Kote-Jarai Z, Easton DF. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013; 45(4):385-91. PMCID: PMC3832790

2. FitzGerald LM, Kumar A, Boyle EA, Zhang Y, McIntosh LM, Kolb S, Stott-Miller M, Smith T, Kayardi D, Ostrander EA, Hsu L, Shendure J, Stanford JL.  Germline missense variants in the BTNL2 gene are associated with prostate cancer susceptibility. Cancer Epidemiol Biom Prev. 2013; 22(9):1520-8. PMCID: PMC3769499

3. Geybels MS, Neuhouser ML, Wright JL, Stott-Miller M, Stanford JL. Coffee and tea consumption in relation to prostate cancer prognosis. Cancer Causes Control. 2013; 24(11):1947-54.  PMCID: PMC3859380

4. Stott-Miller M, Zhao S, Wright JL, Kolb S, Bibikova M, Klotzle B, Ostrander EA, Fan J-B, Feng Z, Stanford JL. Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence. Cancer Epidemiol Biom Prev. 2014; 23(7):1331-39. PMCID: PMC4082437

5. Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; COGS (Collaborative Oncological Gene-environment Study) Consortium; GAME-ON/ELLIPSE Consortium, Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet. 2014; 46(10):1103-09. PMCID: PMC4383163

6. Rubicz R, Zhao S, April C, Wright JL, Kolb S, Coleman I, Lin DW, Nelson PS, Ostrander EA, Feng Z, Fan J-B, Stanford JL. Expression of cell cycle-regulated genes and prostate cancer prognosis in a population-based cohort. The Prostate. 2015; 75(13):1354-62. PMCID: PMC25990700

7. Wright JW, Chéry L, Holt S, Lin DW, Ludeke M, Rincklab AE, Maier C, Stanford JL. Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2: ERG fusion status. Prostate Cancer Prostatic Dis. 2016; 19(1):53-6. PMCID: PMC4942258

8. Karyadi DM, Zhao S, He Q, McIntosh L, Wright JL, Ostrander EA, Feng Z, Stanford JL. Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families. Int J Cancer. 2015; 136(9):2166-71. PMCID: PMC4331209

9. Shui IM, Wong C-J, Zhao S, Kolb S, Ebot EM, Geybels M, Rubicz R, Wright JL, Lin DW, Klotzle B, Bibikova M, Fan J-B, Ostrander EA, Feng Z, Stanford JL. Prostate tumor DNA methylation is associated with cigarette smoking and adverse cancer outcomes. Cancer. 2016; 122(14):2168-77. PMCID: PMC4930391

10. Rubicz R, Zhao S, Geybels M, Wright JL, Kolb S, Klotzle B, Bibikova M, Troyer D, Lance R, Ostrander EA, Feng Z, Fan J-B, Stanford JL. DNA methylation profiles in African American prostate cancer patients in relation to disease progression. Genomics. 2016 Feb 21 [Epub ahead of print]PMCID: PMC4992660

11. Geybels MS, McCloskey KD, Mills IG, Stanford JL. Calcium channel blocker use and risk of prostate cancer by TMPRSS2: ERG gene fusion status. Prostate. 2017; 77(3):282-290. PMID: 27753122

12. Zhao S, Geybels MS, Leonardson A, Rubicz R, Kolb S, Yan Q, Klotzle B, Bibikova M, Hurtado-Coll A, Troyer D, Lance R, Lin DW, Wright JL, Ostrander EA, Fan J-B, Feng Z, Stanford JL. Epigenome-wide tumor DNA methylation profiling identifies novel prognostic biomarkers of metastatic-lethal progression in men diagnosed with clinically localized prostate cancer. Clin Cancer Res. 2017; 23(1):311-319. PMCID: PMC5199634

13. Karyadi DM, Geybels MS, Karlins E, Decker B, McIntosh L, Hutchinson A, Kolb S, McDonnell SK, Hicks B, Middha S, FitzGerald LM, DeRycke MS, Yeager M, Schaid DJ, Chanock SJ, Thibodeau SN, Berndt SI, Stanford JL*, Ostrander EA* (*co-senior authors). Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes. Oncotarget. 2017; 8(1): 1495-1507. PMID: 27902461

14. Rubicz R, Zhao S, Wright JL, Coleman I, Grasso C, Geybels MS, Leonardson A, Kolb S, April C, Bibikova M, Troyer D, Lance R, Lin DW, Ostrander EA, Nelson PS, Fan, J-B, Feng Z, Stanford JL. Gene expression panel predicts metastatic-lethal prostate cancer outcomes in men diagnosed with clinically localized prostate cancer. Mol Oncol. 2017 (in press).



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Janet Stanford, PhD
Photo by Susie Fitzhugh

Contact Information

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(206) 667-2715
Fax
(206) 667-2717
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Mail Stop M4-B874