Search

Your search keyword '"Walsh, Patrick C."' showing total 185 results
Start Over Author "Walsh, Patrick C." Search Limiters Available in Library Collection
185 results on '"Walsh, Patrick C."'

2. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

Author

Giri, Veda N, Knudsen, Karen E, Kelly, William K, Abida, Wassim, Andriole, Gerald L, Bangma, Chris H, Bekelman, Justin E, Benson, Mitchell C, Blanco, Amie, Burnett, Arthur, Catalona, William J, Cooney, Kathleen A, Cooperberg, Matthew, Crawford, David E, Den, Robert B, Dicker, Adam P, Eggener, Scott, Fleshner, Neil, Freedman, Matthew L, Hamdy, Freddie C, Hoffman-Censits, Jean, Hurwitz, Mark D, Hyatt, Colette, Isaacs, William B, Kane, Christopher J, Kantoff, Philip, Karnes, R Jeffrey, Karsh, Lawrence I, Klein, Eric A, Lin, Daniel W, Loughlin, Kevin R, Lu-Yao, Grace, Malkowicz, S Bruce, Mann, Mark J, Mark, James R, McCue, Peter A, Miner, Martin M, Morgan, Todd, Moul, Judd W, Myers, Ronald E, Nielsen, Sarah M, Obeid, Elias, Pavlovich, Christian P, Peiper, Stephen C, Penson, David F, Petrylak, Daniel, Pettaway, Curtis A, Pilarski, Robert, Pinto, Peter A, Poage, Wendy, Raj, Ganesh V, Rebbeck, Timothy R, Robson, Mark E, Rosenberg, Matt T, Sandler, Howard, Sartor, Oliver, Schaeffer, Edward, Schwartz, Gordon F, Shahin, Mark S, Shore, Neal D, Shuch, Brian, Soule, Howard R, Tomlins, Scott A, Trabulsi, Edouard J, Uzzo, Robert, Vander Griend, Donald J, Walsh, Patrick C, Weil, Carol J, Wender, Richard, and Gomella, Leonard G

Subjects
Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Prognosis, Risk Factors, Predictive Value of Tests, Pedigree, Age Factors, Heredity, Phenotype, Adult, Aged, Middle Aged, Male, Genetic Testing, Biomarkers, Tumor, Clinical Decision-Making, Genetics, Aging, Cancer, Prevention, Prostate Cancer, Urologic Diseases, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Published
2018

3. The Melbourne Consensus Statement on the early detection of prostate cancer.

Author

Murphy, Declan G, Ahlering, Thomas, Catalona, William J, Crowe, Helen, Crowe, Jane, Clarke, Noel, Cooperberg, Matthew, Gillatt, David, Gleave, Martin, Loeb, Stacy, Roobol, Monique, Sartor, Oliver, Pickles, Tom, Wootten, Addie, Walsh, Patrick C, and Costello, Anthony J

Subjects
Humans, Prostatic Neoplasms, Prostate-Specific Antigen, Tumor Markers, Biological, Mass Screening, Risk Factors, Consensus, Decision Making, Aged, Middle Aged, Australia, Male, Digital Rectal Examination, Randomized Controlled Trials as Topic, Practice Guidelines as Topic, Early Detection of Cancer, PSA testing, guideline, prostate cancer, risk stratification, screening, Biomarkers, Tumor, Tumor Markers, Biological, Biomarkers, Tumor, Urology & Nephrology, Clinical Sciences
Abstract

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world's leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion. The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.

Published
2014

5. Major Susceptibility Locus for Prostate Cancer on Chromosome 1 Suggested by a Genome-Wide Search

Author

Smith, Jeffrey R., Freije, Diha, Carpten, John D., Grönberg, Henrik, Xu, Jianfeng, Isaacs, Sarah D., Brownstein, Michael J., Bova, G. Steven, Guo, Hong, Bujnovszky, Piroska, Nusskern, Deborah R., Damber, Jan-Erik, Bergh, Anders, Emanuelsson, Monika, Kallioniemi, Olli P., Walker-Daniels, Jennifer, Bailey-Wilson, Joan E., Beaty, Terri H., Meyers, Deborah A., Walsh, Patrick C., Collins, Francis S., Trent, Jeffrey M., and Isaacs, William B.

Published
1996

6. Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

Author

Teerlink, Craig C., Leongamornlert, Daniel, Dadaev, Tokhir, Thomas, Alun, Farnham, James, Stephenson, Robert A., Riska, Shaun, McDonnell, Shannon K., Schaid, Daniel J., Catalona, William J., Zheng, S. Lilly, Cooney, Kathleen A., Ray, Anna M., Zuhlke, Kimberly A., Lange, Ethan M., Giles, Graham G., Southey, Melissa C., Fitzgerald, Liesel M., Rinckleb, Antje, Luedeke, Manuel, Maier, Christiane, Stanford, Janet L., Ostrander, Elaine A., Kaikkonen, Elina M., Sipeky, Csilla, Tammela, Teuvo, Schleutker, Johanna, Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Xu, Jianfeng, Cancel-Tassin, Geraldine, Cussenot, Olivier, Mandal, Diptasri, Laurie, Cecelia, Laurie, Cathy, Thibodeau, Stephen N., Eeles, Rosalind A., Kote-Jarai, Zsofia, Cannon-Albright, Lisa, The PRACTICAL consortium, and International Consortium for Prostate Cancer Genetics

Published
2016
Full Text
View/download PDF

11. Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease

Author

Teerlink, Craig C., Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Rinckleb, Antje, Maier, Christiane, Vogel, Walther, Cancel-Tassin, Geraldine, Egrot, Christophe, Cussenot, Olivier, Foulkes, William D., Giles, Graham G., Hopper, John L., Severi, Gianluca, Eeles, Ros, Easton, Douglas, Kote-Jarai, Zsofia, Guy, Michelle, Cooney, Kathleen A., Ray, Anna M., Zuhlke, Kimberly A., Lange, Ethan M., FitzGerald, Liesel M., Stanford, Janet L., Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Wahlfors, Tiina, Tammela, Teuvo, Schleutker, Johanna, Wiklund, Fredrik, Grönberg, Henrik, Emanuelsson, Monica, Carpten, John, Bailey-Wilson, Joan, Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Catalona, William J., Zheng, S. Lilly, Jin, Guangfu, Lu, Lingyi, Xu, Jianfeng, Camp, Nicola J., Cannon-Albright, Lisa A., and International Consortium for Prostate Cancer Genetics

Published
2014
Full Text
View/download PDF

13. The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients

Author

Na, Rong, primary, Wei, Jun, additional, Sample, Chris J., additional, Gielzak, Marta, additional, Choi, Sodam, additional, Cooney, Kathleen A., additional, Rabizadeh, Daniel, additional, Walsh, Patrick C., additional, Zheng, Lilly S., additional, Xu, Jianfeng, additional, and Isaacs, William B., additional

Published
2021
Full Text
View/download PDF

15. HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)

Author

Xu, Jianfeng, Lange, Ethan M., Lu, Lingyi, Zheng, Siqun L., Wang, Zhong, Thibodeau, Stephen N., Cannon-Albright, Lisa A., Teerlink, Craig C., Camp, Nicola J., Johnson, Anna M., Zuhlke, Kimberly A., Stanford, Janet L., Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Maier, Christiane, Luedeke, Manuel, Vogel, Walther, Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo, Schaid, Daniel, McDonnell, Shannon K., DeRycke, Melissa S., Cancel-Tassin, Geraldine, Cussenot, Olivier, Wiklund, Fredrik, Grönberg, Henrik, Eeles, Ros, Easton, Doug, Kote-Jarai, Zsofia, Whittemore, Alice S., Hsieh, Chih-Lin, Giles, Graham G., Hopper, John L., Severi, Gianluca, Catalona, William J., Mandal, Diptasri, Ledet, Elisa, Foulkes, William D., Hamel, Nancy, Mahle, Lovise, Moller, Pal, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Seminara, Daniela, Cooney, Kathleen A., Isaacs, William B., and International Consortium for Prostate Cancer Genetics

Published
2013
Full Text
View/download PDF

16. Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)

Author

Jin, Guangfu, Lu, Lingyi, Cooney, Kathleen A., Ray, Anna M., Zuhlke, Kimberly A., Lange, Ethan M., Cannon-Albright, Lisa A., Camp, Nicola J., Teerlink, Craig C., FitzGerald, Liesel M., Stanford, Janet L., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Foulkes, William D., Giles, Graham G., Hopper, John L., Severi, Gianluca, Eeles, Ros, Easton, Doug, Kote-Jarai, Zsofia, Guy, Michelle, Rinckleb, Antje, Maier, Christiane, Vogel, Walther, Cancel-Tassin, Geraldine, Egrot, Christophe, Cussenot, Olivier, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Wiklund, Fredrik, Grönberg, Henrik, Emanuelsson, Monica, Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Wahlfors, Tiina, Tammela, Teuvo, Schleutker, Johanna, Catalona, William J., Zheng, S. Lilly, Ostrander, Elaine A., Isaacs, William B., Xu, Jianfeng, and International Consortium for Prostate Cancer Genetics

Published
2012
Full Text
View/download PDF

17. Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect

Author

Chang, Bao-Li, Lange, Ethan M., Dimitrov, Latchezar, Valis, Christopher J., Gillanders, Elizabeth M., Lange, Leslie A., Wiley, Kathleen E., Isaacs, Sarah D., Wiklund, Fredrik, Baffoe-Bonnie, Agnes, Langefeld, Carl D, Zheng, S. Lilly, Matikainen, Mika P., Ikonen, Tarja, Fredriksson, Henna, Tammela, Teuvo, Walsh, Patrick C., Bailey-Wilson, Joan E., Schleutker, Johanna, Gronberg, Henrik, Cooney, Kathleen A., Isaacs, William B., Suh, Edward, Trent, Jeffrey M., and Xu, Jianfeng

Published
2006
Full Text
View/download PDF

19. A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the International Consortium for Prostate Cancer Genetics

Author

Xu, Jianfeng, Dimitrov, Latchezar, Chang, Bao-Li, Adams, Tamara S., Turner, Aubrey R., Meyers, Deborah A., Eeles, Rosalind A., Easton, Douglas F., Foulkes, William D., Simard, Jacques, Giles, Graham G., Hopper, John L., Mahle, Lovise, Moller, Pal, Bishop, Tim, Evans, Chris, Edwards, Steve, Meitz, Julia, Bullock, Sarah, Hope, Questa, Hsieh, Chih-lin, Halpern, Jerry, Balise, Raymond N., Oakley-Girvan, Ingrid, Whittemore, Alice S., Ewing, Charles M., Gielzak, Marta, Isaacs, Sarah D., Walsh, Patrick C., Wiley, Kathleen E., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Cunningham, Julie M., Zarfas, Katherine E., Hebbring, Scott, Schaid, Daniel J., Friedrichsen, Danielle M., Deutsch, Kerry, Kolb, Suzanne, Badzioch, Michael, Jarvik, Gail P., Janer, Marta, Hood, Leroy, Ostrander, Elaine A., Stanford, Janet L., Lange, Ethan M., Beebe-Dimmer, Jennifer L., Mohai, Caroline E., Cooney, Kathleen A., Ikonen, Tarja, Baffoe-Bonnie, Agnes, Fredriksson, Henna, Matikainen, Mika P., Tammela, Teuvo LJ, Bailey-Wilson, Joan, Schleutker, Johanna, Maier, Christiane, Herkommer, Kathleen, Hoegel, Josef J., Vogel, Walther, Paiss, Thomas, Wiklund, Fredrik, Emanuelsson, Monica, Stenman, Elisabeth, Jonsson, Bjorn-Anders, Gronberg, Henrik, Camp, Nicola J., Farnham, James, Cannon-Albright, Lisa A., and Seminara, Daniela

Subjects
Prostate cancer -- Genetic aspects, Human genetics -- Research, Biological sciences
Published
2005

21. Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk

Author

Xu, Jianfeng, Zheng, S. Lilly, Komiya, Akira, Mychaleckyj, Josyf C., Isaacs, Sara D., Chang, Baoli, Turner, Aubrey R., Ewing, Charles M., Wiley, Kathleen E., Hawkins, Gregory A., Bleecker, Eugene R., Walsh, Patrick C., Meyers, Deborah A., and Isaacs, William B.

Subjects
Macrophages -- Physiological aspects, Macrophages -- Genetic aspects, Prostate cancer -- Physiological aspects, Prostate cancer -- Genetic aspects, Gene mutations -- Physiological aspects, Gene mutations -- Health aspects, Biological sciences
Published
2003

23. Linkage of prostate cancer susceptibility loci to chromosome 1

Author

Xu, Jianfeng, Zheng, Siqun L., Chang, Bao-li, Smith, Jeffrey R., Carpten, John D., Stine, O. Colin, Isaacs, Sarah D., Wiley, Kathy E., Henning, Lauren, Ewing, Charles, Bujnovszky, Piroska, Bleeker, Eugene R., Walsh, Patrick C., Trent, Jeffrey M., Meyers, Deborah A., and Isaacs, William B.

Published
2001
Full Text
View/download PDF

25. Two Genome-wide Association Studies of Aggressive Prostate Cancer Implicate Putative Prostate Tumor Suppressor Gene DAB2IP

Author

Duggan, David, Zheng, Siqun L., Knowlton, Michele, Benitez, Debbie, Dimitrov, Latchezar, Wiklund, Fredrik, Robbins, Christiane, Isaacs, Sarah D., Cheng, Yu, Li, Ge, Sun, Jielin, Chang, Bao-Li, Marovich, Leslie, Wiley, Kathleen E., Bälter, Katarina, Stattin, Pär, Adami, Hans-Olov, Gielzak, Marta, Yan, Guifang, Sauvageot, Jurga, Liu, Wennuan, Kim, Jin Woo, Bleecker, Eugene R., Meyers, Deborah A., Trock, Bruce J., Partin, Alan W., Walsh, Patrick C., Isaacs, William B., Grönberg, Henrik, Xu, Jianfeng, and Carpten, John D.

Published
2007

26. Association Between Two Unlinked Loci at 8q24 and Prostate Cancer Risk Among European Americans

Author

Zheng, S. Lilly, Sun, Jielin, Cheng, Yu, Li, Ge, Hsu, Fang-Chi, Zhu, Yi, Chang, Bao-Li, Liu, Wennuan, Kim, Jin Woo, Turner, Aubrey R., Gielzak, Marta, Yan, Guifang, Isaacs, Sarah D., Wiley, Kathleen E., Sauvageot, Jurga, Chen, Huann-Sheng, Gurganus, Robin, Mangold, Leslie A., Trock, Bruce J., Gronberg, Henrik, Duggan, David, Carpten, John D., Partin, Alan W., Walsh, Patrick C., Xu, Jianfeng, and Isaacs, William B.

Published
2007

27. Combined Genome-Wide Scan for Prostate Cancer Susceptibility Genes

Author

Gillanders, Elizabeth M., Xu, Jianfeng, Chang, Bao-li, Lange, Ethan M., Wiklund, Fredrik, Bailey-Wilson, Joan E., Baffoe-Bonnie, Agnes, Jones, MaryPat, Gildea, Derek, Riedesel, Erica, Albertus, Julie, Isaacs, Sarah D., Wiley, Kathleen E., Mohai, Caroline E., Matikainen, Mika P., Tammela, Teuvo L. J., Zheng, S. Lilly, Brown, W. Mark, Rökman, Annika, Carpten, John D., Meyers, Deborah A., Walsh, Patrick C., Schleutker, Johanna, Gronberg, Henrik, Cooney, Kathleen A., Isaacs, William B., and Trent, Jeffrey M.

Published
2004

30. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author

Bailey-Wilson Joan E, Childs Erica J, Cropp Cheryl D, Schaid Daniel J, Xu Jianfeng, Camp Nicola J, Cannon-Albright Lisa A, Farnham James M, George Asha, Powell Isaac, Carpten John D, Giles Graham G, Hopper John L, Severi Gianluca, English Dallas R, Foulkes William D, Mæhle Lovise, Møller Pål, Eeles Rosalind, Easton Douglas, Guy Michelle, Edwards Steve, Badzioch Michael D, Whittemore Alice S, Oakley-Girvan Ingrid, Hsieh Chih-Lin, Dimitrov Latchezar, Stanford Janet L, Karyadi Danielle M, Deutsch Kerry, McIntosh Laura, Ostrander Elaine A, Wiley Kathleen E, Isaacs Sarah D, Walsh Patrick C, Thibodeau Stephen N, McDonnell Shannon K, Hebbring Scott, Lange Ethan M, Cooney Kathleen A, Tammela Teuvo LJ, Schleutker Johanna, Maier Christiane, Bochum Sylvia, Hoegel Josef, Grönberg Henrik, Wiklund Fredrik, Emanuelsson Monica, Cancel-Tassin Geraldine, Valeri Antoine, Cussenot Olivier, and Isaacs William B

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

Published
2012
Full Text
View/download PDF

33. Linkage and Association Studies of Prostate Cancer Susceptibility: Evidence for Linkage at 8p22-23

Author

Xu, Jianfeng, Zheng, Siqun L., Hawkins, Gregory A., Faith, Dennis A., Kelly, Brian, Isaacs, Sarah D., Wiley, Kathleen E., Chang, Bao-li, Ewing, Charles M., Bujnovszky, Piroska, Carpten, John D., Bleecker, Eugene R., Walsh, Patrick C., Trent, Jeffrey M., Meyers, Deborah A., and Isaacs, William B.

Subjects
Prostate cancer -- Genetic aspects, Linkage (Genetics) -- Analysis, Gene expression -- Research, Biological sciences
Published
2001

34. Evaluation of Linkage and Association of HPC2/ELAC2 in Patients with Familial or Sporadic Prostate Cancer

Author

Xu, Jianfeng, Zheng, Siqun L., Carpten, John D., Nupponen, Nina N., Robbins, Christiane M., Mestre, Juanita, Moses, Tracy Y., Faith, Dennis A., Kelly, Brian D., Isaacs, Sarah D., Wiley, Kathleen E., Ewing, Charles M., Bujnovszky, Piroska, Chang, Bao-li, Bailey-Wilson, Joan, Bleecker, Eugene R., Walsh, Patrick C., Trent, Jeffrey M., Meyers, Deborah A., and Isaacs, William B.

Subjects
Prostate cancer -- Genetic aspects, Genetic research -- Analysis, Genetic polymorphisms -- Research, Biological sciences
Published
2001

35. AB68. Novel regulators of testosterone production

Author

Burnett, Arthur L. (Bud) and Walsh, Patrick C.

Subjects
Novel regulators, luteinizing hormone (LH), Testosterone, Podium Lecture
Abstract

In recent years, interest in testosterone replacement therapy for the management of male hypogonadism has grown significantly. This development has paralleled increased public awareness of the signs and symptoms of hypogonadism (also known as low T or low serum testosterone) and the opportunity to address this problem with therapeutic interventions. Conventionally, medical treatment of hypogonadism has been met with various formulations of exogenous testosterone therapies, albeit such therapies do carry limitations. Limitations range from challenges with therapeutic delivery to possible adverse effects. As understanding has grown with respect to regulatory mechanisms of testosterone production and possible new targets for endogenous production of testosterone, new avenues are opening for consideration of therapy particularly in males with primary hypogonadism (low intratesticular testosterone, high serum luteinizing hormone (LH) with low serum testosterone). Several novel molecular pathways have received interest recently as potential pharmacologic targets to increase Leydig cell testosterone production. These pathways and/or signaling molecules include phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin. The advantages of these new targets are suggested to be: (I) maintain an intratesticular testosterone environment that allows /promotes normal spermatogenesis, (II) avoid side effects of exogenous testosterone supplementation, and (III) maintain the negative feedback mechanism of luteinizing hormone (LH) that prevents testosterone levels from becoming supratherapeutic. These novel options are perceived to offer a more targeted and efficacious approach than other suggested interventions to stimulate Leydig cell testosterone production in individuals with primary hypogonadism, such as exogenous LH, human chorionic gonadotropin, and clomiphene, which all act conventionally through the LH receptor. The proposed novel targets offer opportunities to promote increased endogenous testosterone production through the Leydig cell directly without reliance upon functional LH receptors. This approach may involve the application of small molecules, dietary supplements, or even currently available FDA- approved medications, that may exploit newly refined understanding of signaling pathways at the Leydig cell level. It will be of interest to study all of these potential therapeutic prospects further both with careful animal model experimentation and subsequently in human clinical trials.

Published
2014

36. Impact of surgical margin status on prostate-cancer-specific mortality

Author

Chalfin, Heather J., Dinizo, Michael, Trock, Bruce J., Feng, Zhaoyong, Partin, Alan W., Walsh, Patrick C., Humphreys, Elizabeth, and Han, Misop

Subjects
Adult, Male, Prostatectomy, Neoplasm, Residual, Prostatic Neoplasms, Middle Aged, Prostate-Specific Antigen, Article, Survival Rate, Humans, Neoplasm Grading, Neoplasm Recurrence, Local, Aged, Retrospective Studies
Abstract

Study Type--Diagnostic (exploratory cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long-term prostate-cancer-specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15-year prostate-cancer-specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique. This is the first study on the impact of PSM on PCSM in a single surgeon's cohort. In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. In this cohort, men routinely did not receive adjuvant therapy, affording the unique opportunity to study the long-term implications of a PSM.• To examine the relative impact of a positive surgical margin (PSM) and other clinicopathological variables on prostate-cancer-specific mortality (PCSM) in a large retrospective cohort of patients undergoing radical prostatectomy (RP).• Between 1982 and 2011, 4569 men underwent RP performed by a single surgeon. • Of the patient population, 4461 (97.6%) met all the inclusion criteria. • The median (range) age was 58 (33-75) years and the median prostate-specific antigen (PSA) was 5.4 ng/mL; RP Gleason score was ≤ 6 in 2834 (63.7%), 7 in 1351 (30.3%), and 8-10 in 260 (6.0%) patients; PSMs were found in 462 (10.4%) patients. • Cox proportional hazards models were used to determine the impact of a PSM on PCSM.• At a median (range) follow-up of 10 years (1-29), 187 men (4.3%) had died from prostate cancer. • The 20-year prostate-cancer-specific survival rate was 75% for those with a PSM and 93% for those without. • Compared with those with a negative surgical margin, men with a PSM were more likely to be older (median age 60 vs 58 years) and to have undergone RP in the pre-PSA era (36.6% vs 11.8%). Additionally, they were more likely to have a higher PSA level (median 7.6 vs 5.2 ng/mL), a Gleason score of ≥ 7 (58.7% vs 33.7%), and a non-organ-confined tumour (90.9% vs 30.6% [P0.001 for all]). • In a univariate model for PCSM, PSM was highly significant (hazard ratio [HR] 5.0, 95% confidence interval [CI] 3.7-6.7, P0.001). • In a multivariable model, adjusting for pathological variables and RP year, PSM remained an independent predictor of PCSM (HR 1.4, 95% CI 1.0-1.9, P = 0.036) with a modest effect relative to RP Gleason score (HR 5.7-12.6) and pathological stage (HR 2.2-11.0 [P0.001]).• Although a PSM has a statistically significant adverse effect on prostate-cancer-specific survival in multivariable analysis, Gleason grade and pathological stage were stronger predictors.

Published
2012

37. The impact of preoperative erectile dysfunction on survival after radical prostatectomy

Author

Han, Misop, Trock, Bruce J., Partin, Alan W., Humphreys, Elizabeth B., Bivalacqua, Trinity J., Guzzo, Thomas J., and Walsh, Patrick C.

Subjects
Adult, Male, Prostatectomy, Erectile Dysfunction, Humans, Prostatic Neoplasms, Middle Aged, Epidemiologic Methods, Prognosis, Article, Aged
Abstract

Erectile dysfunction (ED) and cardiovascular disease (CVD) share etiology and pathophysiology. The underlying pathology for preoperative ED may adversely affect survival following radical prostatectomy (RP). We examined the association between preoperative ED and survival following RP.Between 1983 and 2000, a single surgeon performed RP on 2511 men, with preoperative ED (ED group, n= 231, 9.2%) or without ED (No ED group, n= 2280, 90.8%). We retrospectively analysed their CVD-specific survival (CVDSS), prostate cancer-specific survival (PCSS), non-PCSS (NPCSS) and overall survival (OS) from time of surgery.With median follow-up of 13 years after RP, 449 men (18%) died (140 from prostate cancer, 309 from other causes). Kaplan-Meier analyses demonstrated significant differences in CVDSS (P0.001), NPCSS (P0.001) and OS (P0.001), but not in PCSS (P= 0.12), between the ED group vs No ED group. In univariate proportional hazards analyses, preoperative ED was associated with a significant decrease in OS, hazard ratio (HR), 1.71 (95% CI, 1.34-2.23), P0.001. However, in multivariable analyses, the association of ED with survival became non-significant (HR, 1.25 (95% CI, 0.97-1.66), P= 0.111) after adjusting for other prognostic factors, such as age, preoperative prostate-specific antigen (PSA) level, Gleason score, pathologic stage, body mass index and Charlson Comorbidity Index.Preoperative ED is associated with decreased overall survival and survival from causes other than prostate cancer following RP. However, preoperative ED was not an independent predictor of overall survival after adjusting for other predictors of survival. Urologists should carefully assess pretreatment ED status to enhance appropriate treatment recommendation for men with prostate cancer.

Published
2010

38. Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

Author

Kader, A. Karim, Sun, Jielin, Isaacs, Sarah D., Wiley, Kathleen E., Yan, Guifang, Kim, Seong-Tae, Fedor, Helen, DeMarzo, Angelo M., Epstein, Jonathan I., Walsh, Patrick C., Partin, Alan W., Trock, Bruce, Zheng, S. Lilly, Xu, Jianfeng, and Isaacs, William

Subjects
Male, Prostatectomy, Genotype, Prostatic Neoplasms, Prostatic Secretory Proteins, Middle Aged, Prostate-Specific Antigen, Polymorphism, Single Nucleotide, Article, Cohort Studies, Gene Frequency, Predictive Value of Tests, Risk Factors, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Retrospective Studies
Abstract

More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive.Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol.For 18 of the 20 SNPs examined, no statistically significant differences (P0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scoresor =4 + 3, or stageor =T3b, or N+) or less aggressive disease (Gleason scoresor =3 + 4, and stageor =T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 x 10(-7)) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA.The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa.

Published
2009

39. Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations

Author

Sun, Jielin, Chang, Bao-Li, Isaacs, Sarah D., Wiley, Kathleen E., Wiklund, Fredrik, Stattin, Pär, Duggan, David, Carpten, John D., Trock, Bruce J., Partin, Alan W., Walsh, Patrick C., Grönberg, Henrik, Xu, Jianfeng, Isaacs, William B., and Zheng, S. Lilly

Subjects
Aged, 80 and over, Male, Prostatic Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Article, United States, Case-Control Studies, Biomarkers, Tumor, Odds Ratio, Humans, Genetic Predisposition to Disease, Aged, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 8
Abstract

A strong cumulative effect of five genetic variants and family history on prostate cancer risk was recently reported in a Swedish population (CAPS). We carried out this study to confirm the finding in two U.S. study populations and perform a combined analysis to obtain a more stable estimate of the odds ratio (OR) for prostate cancer.We evaluated three SNPs at 8q24 and one SNP each at 17q12 and 17q24.3 in two study populations in the U.S. The first was a hospital-based case-control study population at Johns Hopkins Hospital (JHH), including 1,563 prostate cancer patients and 576 control subjects. The second was the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, including 1,172 prostate cancer patients and 1,157 control subjects.We confirmed a cumulative effect of five risk variants on prostate cancer risk. Based on a total of 5,628 cases and 3,514 controls from JHH, CGEMS, and CAPS, men who carry any combination of 1, 2, 3, and 4 or more of these five risk variants have an estimated OR (95% CI) of 1.41 (1.20-1.67), 1.88 (1.59-2.22), 2.36 (1.95-2.85), and 3.80 (2.77-5.22) for prostate cancer, respectively, compared to men who do not have any of these five risk variants. When family history was included, the cumulative effect was stronger.These results provide an important confirmation for the cumulative effect of five genetic risk variants on prostate cancer risk. The more stable OR estimates of the cumulative effect of these six risk factors are a major step toward individual risk characterization for this disease.

Published
2008

40. Association of variants at two 17q loci with prostate cancer risk in European and African Americans

Author

Sun, Jielin, Purcell, Lina, Gao, Zhengrong, Isaacs, Sarah D., Wiley, Kathleen E., Hsu, Fang-Chi, Liu, Wennuan, Duggan, David, Carpten, John D., Grönberg, Henrik, Xu, Jianfeng, Chang, Bao-Li, Partin, Alan W., Walsh, Patrick C., Isaacs, William B., and Zheng, S. Lilly

Subjects
Male, Maryland, Prostatic Neoplasms, Middle Aged, Prostate-Specific Antigen, Polymorphism, Single Nucleotide, Risk Assessment, Article, White People, Black or African American, Case-Control Studies, Odds Ratio, Humans, Genetic Predisposition to Disease, Chromosomes, Human, Pair 17
Abstract

Multiple SNPs at 17q12 and 17q24.3 were recently identified to be associated with prostate cancer risk using a genome-wide association study. Although these associations reached genome-wide significance level in a combined analysis of several study populations of European descent in the original report, confirmation in independent populations, including African Americans (AA), is critical to increase confidence that they represent true disease associations and whether the results can be generalized. Therefore, we evaluated these 7 SNPs in two populations recruited from Johns Hopkins Hospital, including European Americans (EA) (1,563 cases and 576 controls) and AA (364 cases and 353 controls). Each of the previously reported risk alleles of these 7 SNPs were more common in cases than in controls among EA and AA. The differences were highly significant in EA (P = 10−4) and marginally significant in AA (P = 0.04) for 17q12SNPs. In contrast, the differences were not statistically significant in EA or AA for SNPs at 17q24.3, but were marginally significant for two SNPs (P = 0.04 - 0.06) when subjects from EA and AA were combined. Similar results were obtained for genotype and haplotype frequencies. These risk variants were not associated with aggressiveness of prostate cancer or other clinical variables such as TNM stage, pre-operative PSA, or age at diagnosis. Our results provide the first confirmation of these novel prostate loci and the first demonstration that these two loci may also play roles in prostate cancer risk among AA.

Published
2008

41. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author

Bailey-Wilson, Joan E, Childs, Erica J, Cropp, Cheryl D, Schaid, Daniel J, Xu, Jianfeng, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, George, Asha, Powell, Isaac, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Rosalind, Easton, Douglas, Guy, Michelle, Edwards, Steve, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Stanford, Janet L, Karyadi, Danielle M, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo LJ, Schleutker, Johanna, Maier, Christiane, Bochum, Sylvia, Hoegel, Josef, Gronberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Isaacs, William B, Bailey-Wilson, Joan E, Childs, Erica J, Cropp, Cheryl D, Schaid, Daniel J, Xu, Jianfeng, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, George, Asha, Powell, Isaac, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Rosalind, Easton, Douglas, Guy, Michelle, Edwards, Steve, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Stanford, Janet L, Karyadi, Danielle M, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo LJ, Schleutker, Johanna, Maier, Christiane, Bochum, Sylvia, Hoegel, Josef, Gronberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, and Isaacs, William B

Abstract

Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. O

Published
2012
Full Text
View/download PDF

42. Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

Author

Lu, Lingyi, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Lange, Ethan M., Cooney, Kathleen A., Farnham, James M., Camp, Nicola J., Cannon-Albright, Lisa A., Tammela, Teuvo L. J., Schleutker, Johanna, Hoegel, Josef, Herkommer, Kathleen, Maier, Christiane, Vogel, Walther, Wiklund, Fredrik, Emanuelsson, Monica, Groenberg, Henrik, Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Helfand, Brian T., Kan, Donghui, Catalona, William J., Stanford, Janet L., FitzGerald, Liesel M., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Powell, Isaac, Bailey-Wilson, Joan E., Cropp, Cheryl D., Simpson, Claire, Carpten, John D., Seminara, Daniela, Zheng, S. Lilly, Xu, Jianfen, Giles, Graham G., Severi, Gianluca, Hopper, John L., English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Badzioch, Michael D., Edwards, Steve, Guy, Michelle, Eeles, Ros, Easton, Douglas, Isaacs, William B., Lu, Lingyi, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Lange, Ethan M., Cooney, Kathleen A., Farnham, James M., Camp, Nicola J., Cannon-Albright, Lisa A., Tammela, Teuvo L. J., Schleutker, Johanna, Hoegel, Josef, Herkommer, Kathleen, Maier, Christiane, Vogel, Walther, Wiklund, Fredrik, Emanuelsson, Monica, Groenberg, Henrik, Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Helfand, Brian T., Kan, Donghui, Catalona, William J., Stanford, Janet L., FitzGerald, Liesel M., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Powell, Isaac, Bailey-Wilson, Joan E., Cropp, Cheryl D., Simpson, Claire, Carpten, John D., Seminara, Daniela, Zheng, S. Lilly, Xu, Jianfen, Giles, Graham G., Severi, Gianluca, Hopper, John L., English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Badzioch, Michael D., Edwards, Steve, Guy, Michelle, Eeles, Ros, Easton, Douglas, and Isaacs, William B.

Abstract

BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.

Published
2012
Full Text
View/download PDF

43. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.

Author

Christensen, G Bryce, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Isaacs, William B, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M, Cannon-Albright, Lisa A, Camp, Nicola J, Christensen, G Bryce, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Isaacs, William B, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M, Cannon-Albright, Lisa A, and Camp, Nicola J

Abstract

BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.

Published
2010
Full Text
View/download PDF

44. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author

University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., Camp, Nicola J., University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.

Abstract

BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11???q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9???cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735???744, 2010. ?? 2010 Wiley-Liss, Inc.

Published
2010

45. A novel prostate cancer susceptibility locus at 19q13.

Author

Hsu, Fang-Chi, Sun, Jielin, Wiklund, Fredrik, Isaacs, Sarah D, Wiley, Kathleen E, Purcell, Lina D, Gao, Zhengrong, Stattin, Pär, Zhu, Yi, Kim, Seong-Tae, Zhang, Zheng, Liu, Wennuan, Chang, Bao-Li, Walsh, Patrick C, Duggan, David, Carpten, John D, Isaacs, William B, Grönberg, Henrik, Xu, Jianfeng, Zheng, S Lilly, Hsu, Fang-Chi, Sun, Jielin, Wiklund, Fredrik, Isaacs, Sarah D, Wiley, Kathleen E, Purcell, Lina D, Gao, Zhengrong, Stattin, Pär, Zhu, Yi, Kim, Seong-Tae, Zhang, Zheng, Liu, Wennuan, Chang, Bao-Li, Walsh, Patrick C, Duggan, David, Carpten, John D, Isaacs, William B, Grönberg, Henrik, Xu, Jianfeng, and Zheng, S Lilly

Abstract

A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (n=2,393) and controls (n=1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P=9.4 x 10(-4)). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 x 10(-7) from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.

Published
2009
Full Text
View/download PDF

46. Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12.

Author

Sun, Jielin, Zheng, Siqun Lilly, Wiklund, Fredrik, Isaacs, Sarah D, Purcell, Lina D, Gao, Zhengrong, Hsu, Fang-Chi, Kim, Seong-Tae, Liu, Wennuan, Zhu, Yi, Stattin, Pär, Adami, Hans-Olov, Wiley, Kathleen E, Dimitrov, Latchezar, Sun, Jishan, Li, Tao, Turner, Aubrey R, Adams, Tamara S, Adolfsson, Jan, Johansson, Jan-Erik, Lowey, James, Trock, Bruce J, Partin, Alan W, Walsh, Patrick C, Trent, Jeffrey M, Duggan, David, Carpten, John, Chang, Bao-Li, Grönberg, Henrik, Isaacs, William B, Xu, Jianfeng, Sun, Jielin, Zheng, Siqun Lilly, Wiklund, Fredrik, Isaacs, Sarah D, Purcell, Lina D, Gao, Zhengrong, Hsu, Fang-Chi, Kim, Seong-Tae, Liu, Wennuan, Zhu, Yi, Stattin, Pär, Adami, Hans-Olov, Wiley, Kathleen E, Dimitrov, Latchezar, Sun, Jishan, Li, Tao, Turner, Aubrey R, Adams, Tamara S, Adolfsson, Jan, Johansson, Jan-Erik, Lowey, James, Trock, Bruce J, Partin, Alan W, Walsh, Patrick C, Trent, Jeffrey M, Duggan, David, Carpten, John, Chang, Bao-Li, Grönberg, Henrik, Isaacs, William B, and Xu, Jianfeng

Published
2008

47. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer.

Author

Gudmundsson, Julius, Sulem, Patrick, Rafnar, Thorunn, Bergthorsson, Jon T, Manolescu, Andrei, Gudbjartsson, Daniel, Agnarsson, Bjarni A, Sigurdsson, Asgeir, Benediktsdottir, Kristrun R, Blondal, Thorarinn, Jakobsdottir, Margret, Stacey, Simon N, Kostic, Jelena, Kristinsson, Kari T, Birgisdottir, Birgitta, Ghosh, Shyamali, Magnusdottir, Droplaug N, Thorlacius, Steinunn, Thorleifsson, Gudmar, Zheng, S Lilly, Sun, Jielin, Chang, Bao-Li, Elmore, J Bradford, Breyer, Joan P, McReynolds, Kate M, Bradley, Kevin M, Yaspan, Brian L, Wiklund, Fredrik, Stattin, Pär, Lindström, Sara, Adami, Hans-Olov, McDonnell, Shannon K, Schaid, Daniel J, Cunningham, Julie M, Wang, Liang, Cerhan, James R, St Sauver, Jennifer L, Isaacs, Sara D, Wiley, Kathleen E, Partin, Alan W, Walsh, Patrick C, Polo, Sonia, Ruiz-Echarri, Manuel, Navarrete, Sebastian, Fuertes, Fernando, Saez, Berta, Godino, Javier, Weijerman, Philip C, Swinkels, Dorine W, Aben, Katja K, Witjes, J Alfred, Suarez, Brian K, Helfand, Brian T, Frigge, Michael L, Kristjansson, Kristleifur, Ober, Carole, Jonsson, Eirikur, Einarsson, Gudmundur V, Xu, Jianfeng, Gronberg, Henrik, Smith, Jeffrey R, Thibodeau, Stephen N, Isaacs, William B, Catalona, William J, Mayordomo, Jose I, Kiemeney, Lambertus A, Barkardottir, Rosa B, Gulcher, Jeffrey R, Thorsteinsdottir, Unnur, Kong, Augustine, Stefansson, Kari, Gudmundsson, Julius, Sulem, Patrick, Rafnar, Thorunn, Bergthorsson, Jon T, Manolescu, Andrei, Gudbjartsson, Daniel, Agnarsson, Bjarni A, Sigurdsson, Asgeir, Benediktsdottir, Kristrun R, Blondal, Thorarinn, Jakobsdottir, Margret, Stacey, Simon N, Kostic, Jelena, Kristinsson, Kari T, Birgisdottir, Birgitta, Ghosh, Shyamali, Magnusdottir, Droplaug N, Thorlacius, Steinunn, Thorleifsson, Gudmar, Zheng, S Lilly, Sun, Jielin, Chang, Bao-Li, Elmore, J Bradford, Breyer, Joan P, McReynolds, Kate M, Bradley, Kevin M, Yaspan, Brian L, Wiklund, Fredrik, Stattin, Pär, Lindström, Sara, Adami, Hans-Olov, McDonnell, Shannon K, Schaid, Daniel J, Cunningham, Julie M, Wang, Liang, Cerhan, James R, St Sauver, Jennifer L, Isaacs, Sara D, Wiley, Kathleen E, Partin, Alan W, Walsh, Patrick C, Polo, Sonia, Ruiz-Echarri, Manuel, Navarrete, Sebastian, Fuertes, Fernando, Saez, Berta, Godino, Javier, Weijerman, Philip C, Swinkels, Dorine W, Aben, Katja K, Witjes, J Alfred, Suarez, Brian K, Helfand, Brian T, Frigge, Michael L, Kristjansson, Kristleifur, Ober, Carole, Jonsson, Eirikur, Einarsson, Gudmundur V, Xu, Jianfeng, Gronberg, Henrik, Smith, Jeffrey R, Thibodeau, Stephen N, Isaacs, William B, Catalona, William J, Mayordomo, Jose I, Kiemeney, Lambertus A, Barkardottir, Rosa B, Gulcher, Jeffrey R, Thorsteinsdottir, Unnur, Kong, Augustine, and Stefansson, Kari

Published
2008

48. Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics.

Author

Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Isaacs, William B, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, Baffoe-Bonnie, Agnes B, George, Asha, Powell, Isaac, Bailey-Wilson, Joan E, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L, Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Schaid, Daniel J, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo L J, Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, and Isaacs, William B

Published
2007
Full Text
View/download PDF

49. Two-locus genome-wide linkage scan for prostate cancer susceptibility genes with an interaction effect

Author

Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, ; Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, ; Medical Center Blvd, Winston-Salem, NC, 27157, USA, ; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Radiation Sciences, Oncology, University of Ume??, Ume??, Sweden, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, ; Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA, Ann Arbor, Isaacs, William B., Cooney, Kathleen A., Wiley, Kathleen E., Trent, Jeffrey M., Dimitrov, Latchezar, Chang, Bao-Li, Lange, Ethan M., Suh, Edward, Gillanders, Elizabeth M., Lange, Leslie A., Xu, Jianfeng, Valis, Christopher J., Baffoe-Bonnie, Agnes, Zheng, S. Lilly, Fredriksson, Henna, Matikainen, Mika P., Gronberg, Henrik, Tammela, Teuvo, Bailey-Wilson, Joan E., Walsh, Patrick C., Schleutker, Johanna, Ikonen, Tarja, Langefeld, Carl D., Isaacs, Sarah D., Wiklund, Fredrik, Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, ; Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, ; Medical Center Blvd, Winston-Salem, NC, 27157, USA, ; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Radiation Sciences, Oncology, University of Ume??, Ume??, Sweden, Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland, ; Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA, Ann Arbor, Isaacs, William B., Cooney, Kathleen A., Wiley, Kathleen E., Trent, Jeffrey M., Dimitrov, Latchezar, Chang, Bao-Li, Lange, Ethan M., Suh, Edward, Gillanders, Elizabeth M., Lange, Leslie A., Xu, Jianfeng, Valis, Christopher J., Baffoe-Bonnie, Agnes, Zheng, S. Lilly, Fredriksson, Henna, Matikainen, Mika P., Gronberg, Henrik, Tammela, Teuvo, Bailey-Wilson, Joan E., Walsh, Patrick C., Schleutker, Johanna, Ikonen, Tarja, Langefeld, Carl D., Isaacs, Sarah D., and Wiklund, Fredrik

Abstract

Prostate cancer represents a significant worldwide public health burden. Epidemiological and genetic epidemiological studies have consistently provided data supporting the existence of inherited prostate cancer susceptibility genes. Segregation analyses of prostate cancer suggest that a multigene model may best explain familial clustering of this disease. Therefore, modeling gene???gene interactions in linkage analysis may improve the power to detect chromosomal regions harboring these disease susceptibility genes. In this study, we systematically screened for prostate cancer linkage by modeling two-locus gene???gene interactions for all possible pairs of loci across the genome in 426 prostate cancer families from Johns Hopkins Hospital, University of Michigan, University of Ume??, and University of Tampere. We found suggestive evidence for an epistatic interaction for six sets of loci (target chromosome-wide/reference marker-specific P???0.0001). Evidence for these interactions was found in two independent subsets from within the 426 families. While the validity of these results requires confirmation from independent studies and the identification of the specific genes underlying this linkage evidence, our approach of systematically assessing gene???gene interactions across the entire genome represents a promising alternative approach for gene identification for prostate cancer.

Published
2006

50. Combined genome-wide scan for prostate cancer susceptibility genes

Author

Gillanders, Elizabeth M, Xu, Jianfeng, Chang, Bao-li, Lange, Ethan M, Wiklund, Fredrik, Bailey-Wilson, Joan E, Baffoe-Bonnie, Agnes, Jones, MaryPat, Gildea, Derek, Riedesel, Erica, Albertus, Julie, Isaacs, Sarah D, Wiley, Kathleen E, Mohai, Caroline E, Matikainen, Mika P, Tammela, Teuvo L J, Zheng, S Lilly, Brown, W Mark, Rökman, Annika, Carpten, John D, Meyers, Deborah A, Walsh, Patrick C, Schleutker, Johanna, Grönberg, Henrik, Cooney, Kathleen A, Isaacs, William B, Trent, Jeffrey M, Gillanders, Elizabeth M, Xu, Jianfeng, Chang, Bao-li, Lange, Ethan M, Wiklund, Fredrik, Bailey-Wilson, Joan E, Baffoe-Bonnie, Agnes, Jones, MaryPat, Gildea, Derek, Riedesel, Erica, Albertus, Julie, Isaacs, Sarah D, Wiley, Kathleen E, Mohai, Caroline E, Matikainen, Mika P, Tammela, Teuvo L J, Zheng, S Lilly, Brown, W Mark, Rökman, Annika, Carpten, John D, Meyers, Deborah A, Walsh, Patrick C, Schleutker, Johanna, Grönberg, Henrik, Cooney, Kathleen A, Isaacs, William B, and Trent, Jeffrey M

Published
2004
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results