Vanderbilt-Ingram Cancer Center

The VICC.ORG Investigator Directory

Jeffrey R. Smith, M.D., Ph.D.

See also:

• Breast Cancer Research Program
• Medicine: Genetic Medicine
• BRET: Biomedical Research Education & Training Faculty Listing
• PubMed Listing of Dr. Smith's Publications

Assistant Professor of Medicine (Genetic Medicine) and Cancer Biology
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
451 Preston Building
Nashville, TN 37232-6304
615-936-2660

Research Specialty:

Genetics and genomics of cancer

Research Description:

Our research group is conducting three separate large-scale genomic investigations: 



The first is a collaborative project to determine genetic causes of breast cancer within the well-established Nashville Breast Cohort. The cohort of over 7000 women has been followed for two decades for the development of breast cancer. Drs. David Page and William Dupont contribute pathologic and epidemiologic analyses while our laboratory is conducting genomic and statistical genetic analyses. Each of these efforts are part of the larger Vanderbilt-Ingram Cancer Center's Breast Cancer SPORE. Genetics offers a systematic framework for the discovery of key risk components of well-studied cancer pathways, as well as for the discovery of novel breast cancer genes. 



The second project originated within our laboratory to identify genetic causes of prostate cancer. We have assembled a study population of 2000 men from families particularly burdened with prostate cancer, as well as men from families free of any history of prostate cancer. We are investigating candidate genes from cancer pathways as well as genomic intervals highlighted by our prior genome-wide scan of hereditary prostate cancer pedigrees. These investigations are yielding discoveries of the strong genetic component underlying prostate cancer. 



Our third project has developed genetic mapping resources for zebrafish as a vertebrate model organism. We discovered ~4 million SNPs, developed a high-resolution SNP-based genetic map, characterized genomic diversity of common laboratory strains, and concurrently identified the sex-determination loci of zebrafish.



Our laboratory is also involved in a wide array of collaborative genetics projects.

Clinical Interest:

Prostate and Breast Cancer Genetics

Clincial Research Description:

Our research group is conducting three separate large-scale genomic investigations: 

 The first is a collaborative project to determine genetic causes of breast cancer within the well-established Nashville Breast Cohort. The cohort of over 7000 women has been followed for two decades for the development of breast cancer. Drs. David Page and William Dupont contribute pathologic and epidemiologic analyses while our laboratory is conducting genomic and statistical genetic analyses. Each of these efforts are part of the larger Vanderbilt-Ingram Cancer Center's Breast Cancer SPORE. Genetics offers a systematic framework for the discovery of key risk components of well-studied cancer pathways, as well as for the discovery of novel breast cancer genes. 

 The second project originated within our laboratory to identify genetic causes of prostate cancer. We have assembled a study population of 2000 men from families particularly burdened with prostate cancer, as well as men from families free of any history of prostate cancer. We are investigating candidate genes from cancer pathways as well as genomic intervals highlighted by our prior genome-wide scan of hereditary prostate cancer pedigrees. These investigations are yielding discoveries of the strong genetic component underlying prostate cancer. 

 Our third project has developed genetic mapping resources for zebrafish as a vertebrate model organism. We discovered ~4 million SNPs, developed a high-resolution SNP-based genetic map, characterized genomic diversity of common laboratory strains, and concurrently identified the sex-determination loci of zebrafish.

 Our laboratory is also involved in a wide array of collaborative genetics projects.

Publications:

• Higginbotham, KS, Breyer, JP, Bradley, KM, Schuyler, PA, Plummer, WD, Freudenthal, ME, Trentham-Dietz, A, Newcomb, PA, Sanders, ME, Page, DL, Parl, FF, Egan, KM, Dupont, WD, Smith, JR A Multistage Association Study Identifies a Breast Cancer Genetic Locus at NCOA7. Cancer Res, 71(11), 3881-3888, 2011.
• Cohen, SS, Gammon, MD, North, KE, Millikan, RC, Lange, EM, Williams, SM, Zheng, W, Cai, Q, Long, J, Smith, JR, Signorello, LB, Blot, WJ, Matthews, CE ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and BMI in Black and White Women. Obesity (Silver Spring), 2011.
• Signorello, LB, Williams, SM, Zheng, W, Smith, JR, Long, J, Cai, Q, Hargreaves, MK, Hollis, BW, Blot, WJ Blood vitamin d levels in relation to genetic estimation of African ancestry. Cancer Epidemiol Biomarkers Prev, 19(9), 2325-31, 2010.
• Dupont, WD, Breyer, JP, Bradley, KM, Schuyler, PA, Plummer, WD, Sanders, ME, Page, DL, Smith, JR Protein phosphatase 2A subunit gene haplotypes and proliferative breast disease modify breast cancer risk. Cancer, 116(1), 8-19, 2010.
• Love, HD, Booton, SE, Boone, BE, Breyer, JP, Koyama, T, Revelo, MP, Shappell, SB, Smith, JR, Hayward, SW Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer. PLoS One, 4(12), e8384, 2009.
• Breyer, JP, McReynolds, KM, Yaspan, BL, Bradley, KM, Dupont, WD, Smith, JR Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes. Cancer Epidemiol Biomarkers Prev, 18(7), 2137-44, 2009.
• Gudmundsson, J, Sulem, P, Gudbjartsson, DF, Blondal, T, Gylfason, A, Agnarsson, BA, Benediktsdottir, KR, Magnusdottir, DN, Orlygsdottir, G, Jakobsdottir, M, Stacey, SN, Sigurdsson, A, Wahlfors, T, Tammela, T, Breyer, JP, McReynolds, KM, Bradley, KM, Saez, B, Godino, J, Navarrete, S, Fuertes, F, Murillo, L, Polo, E, Aben, KK, van Oort, IM, Suarez, BK, Helfand, BT, Kan, D, Zanon, C, Frigge, ML, Kristjansson, K, Gulcher, JR, Einarsson, GV, Jonsson, E, Catalona, WJ, Mayordomo, JI, Kiemeney, LA, Smith, JR, Schleutker, J, Barkardottir, RB, Kong, A, Thorsteinsdottir, U, Rafnar, T, Stefansson, K Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet, 41(10), 1122-6, 2009.
• Breyer, JP, Sanders, ME, Airey, DC, Cai, Q, Yaspan, BL, Schuyler, PA, Dai, Q, Boulos, F, Olivares, MG, Bradley, KM, Gao, YT, Page, DL, Dupont, WD, Zheng, W, Smith, JR Heritable variation of ERBB2 and breast cancer risk. Cancer Epidemiol Biomarkers Prev, 18(4), 1252-8, 2009.
• Yaspan, BL, McReynolds, KM, Elmore, JB, Breyer, JP, Bradley, KM, Smith, JR A haplotype at chromosome Xq27.2 confers susceptibility to prostate cancer. Hum Genet, 123(4), 379-86, 2008.
• Ye, C, Gao, YT, Wen, W, Breyer, JP, Shu, XO, Smith, JR, Zheng, W, Cai, Q Association of mitochondrial DNA displacement loop (CA)n dinucleotide repeat polymorphism with breast cancer risk and survival among Chinese women. Cancer Epidemiol Biomarkers Prev, 17(8), 2117-22, 2008.
• Gudmundsson, J, Sulem, P, Rafnar, T, Bergthorsson, JT, Manolescu, A, Gudbjartsson, D, Agnarsson, BA, Sigurdsson, A, Benediktsdottir, KR, Blondal, T, Jakobsdottir, M, Stacey, SN, Kostic, J, Kristinsson, KT, Birgisdottir, B, Ghosh, S, Magnusdottir, DN, Thorlacius, S, Thorleifsson, G, Zheng, SL, Sun, J, Chang, BL, Elmore, JB, Breyer, JP, McReynolds, KM, Bradley, KM, Yaspan, BL, Wiklund, F, Stattin, P, Lindström, S, Adami, HO, McDonnell, SK, Schaid, DJ, Cunningham, JM, Wang, L, Cerhan, JR, St Sauver, JL, Isaacs, SD, Wiley, KE, Partin, AW, Walsh, PC, Polo, S, Ruiz-Echarri, M, Navarrete, S, Fuertes, F, Saez, B, Godino, J, Weijerman, PC, Swinkels, DW, Aben, KK, Witjes, JA, Suarez, BK, Helfand, BT, Frigge, ML, Kristjansson, K, Ober, C, Jonsson, E, Einarsson, GV, Xu, J, Gronberg, H, Smith, JR, Thibodeau, SN, Isaacs, WB, Catalona, WJ, Mayordomo, JI, Kiemeney, LA, Barkardottir, RB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Stefansson, K Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet, 40(3), 281-3, 2008.
• Ciarleglio, CM, Ryckman, KK, Servick, SV, Hida, A, Robbins, S, Wells, N, Hicks, J, Larson, SA, Wiedermann, JP, Carver, K, Hamilton, N, Kidd, KK, Kidd, JR, Smith, JR, Friedlaender, J, McMahon, DG, Williams, SM, Summar, ML, Johnson, CH Genetic Differences in Human Circadian Clock Genes among Worldwide Populations. J Biol Rhythms, 23(4), 330-40, 2008.
• Cai, Q, Kataoka, N, Li, C, Wen, W, Smith, JR, Gao, YT, Shu, XO, Zheng, W Haplotype analyses of CYP19A1 gene variants and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev, 17(1), 27-32, 2008.
• Bradley, KM, Elmore, JB, Breyer, JP, Yaspan, BL, Jessen, JR, Knapik, EW, Smith, JR A major zebrafish polymorphism resource for genetic mapping. Genome Biol, 8(4), R55, 2007.
• Yaspan, BL, Breyer, JP, Cai, Q, Dai, Q, Elmore, JB, Amundson, I, Bradley, KM, Shu, XO, Gao, YT, Dupont, WD, Zheng, W, Smith, JR Haplotype analysis of CYP11A1 identifies promoter variants associated with breast cancer risk. Cancer Res, 67(12), 5673-82, 2007.
• Baffoe-Bonnie*, AB, Smith*, JR, Stephan, DA, Schleutker, J, Carpten, JD, Kainu, T, Gillanders, EM, Matikainen, M, Teslovich, TM, Tammela, T, Sood, R, Balshem, AM, Scarborough, SD, Xu, J, Isaacs, WB, Trent, JM, Kallioniemi, OP, Bailey-Wilson, JE A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region. Hum Genet, 117(4), 307-16, 2005.
• Owens, SE, Broman, KW, Wiltshire, T, Elmore, JB, Bradley, KM, Smith, JR, Southard-Smith, EM Genome-wide linkage identifies novel modifier loci of aganglionosis in the Sox10Dom model of Hirschsprung disease. Hum Mol Genet, 14(11), 1549-58, 2005.
• Wen, W, Gao, YT, Shu, XO, Yu, H, Cai, Q, Smith, JR, Zheng, W Insulin-like growth factor-I gene polymorphism and breast cancer risk in Chinese women. Int J Cancer, 113(2), 307-11, 2005.
• Boyapati, SM, Shu, XO, Ruan, ZX, Cai, Q, Smith, JR, Wen, W, Gao, YT, Zheng, W Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival. Clin Cancer Res, 11(3), 1093-8, 2005.
• Adegoke, OJ, Shu, XO, Gao, YT, Cai, Q, Breyer, J, Smith, J, Zheng, W Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. Breast Cancer Res Treat, 85(3), 239-45, 2004.
• Cantrell, VA, Owens, SE, Chandler, RL, Airey, DC, Bradley, KM, Smith, JR, Southard-Smith, EM Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Hum Mol Genet, 13(19), 2289-301, 2004.
• Zheng, W, Gao, YT, Shu, XO, Wen, W, Cai, Q, Dai, Q, Smith, JR Population-based case-control study of CYP11A gene polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev, 13(5), 709-14, 2004.
• Cai, Q, Gao, YT, Wen, W, Shu, XO, Jin, F, Smith, JR, Zheng, W Association of breast cancer risk with a GT dinucleotide repeat polymorphism upstream of the estrogen receptor-alpha gene. Cancer Res, 63(18), 5727-30, 2003.
• Carpten, J, Nupponen, N, Isaacs, S, Sood, R, Robbins, C, Xu, J, Faruque, M, Moses, T, Ewing, C, Gillanders, E, Hu, P, Bujnovszky, P, Makalowska, I, Baffoe-Bonnie, A, Faith, D, Smith, J, Stephan, D, Wiley, K, Brownstein, M, Gildea, D, Kelly, B, Jenkins, R, Hostetter, G, Matikainen, M, Schleutker, J, Klinger, K, Connors, T, Xiang, Y, Wang, Z, De Marzo, A, Papadopoulos, N, Kallioniemi, OP, Burk, R, Meyers, D, Gronberg, H, Meltzer, P, Silverman, R, Bailey-Wilson, J, Walsh, P, Isaacs, W, Trent, J Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet, 30(2), 181-4, 2002.
• Smith, J., Collins, F., and Gelehrter, T "Molecular Genetics of Common Disease. In: The Genetic Basis of Common Diseases, Second Edition, edited by King, Rotter, and Motulsky." (Oxford Univesity Press), 2002.
• Stephan, DA, Howell, GR, Teslovich, TM, Coffey, AJ, Smith, L, Bailey-Wilson, JE, Malechek, L, Gildea, D, Smith, JR, Gillanders, EM, Schleutker, J, Hu, P, Steingruber, HE, Dhami, P, Robbins, CM, Makalowska, I, Carpten, JD, Sood, R, Mumm, S, Reinbold, R, Bonner, TI, Baffoe-Bonnie, A, Bubendorf, L, Heiskanen, M, Kallioneimi, OP, Baxevanis, AD, Joseph, SS, Zucchi, I, Burk, RD, Isaacs, W, Ross, MT, Trent, JM Physical and transcript map of the hereditary prostate cancer region at xq27. Genomics, 79(1), 41-50, 2002.
• Ho, GY, Knapp, M, Freije, D, Nelson, WG, Smith, JR, Carpten, JD, Bailey-Wilson, JE, Beaty, TH, Petersen, G, Xu, J, Kamensky, V, Walsh, PC, Isaacs, WB Transmission/disequilibrium tests of androgen receptor and glutathione S-transferase pi variants in prostate cancer families. Int J Cancer, 98(6), 938-42, 2002.
• Xu, J, Zheng, SL, Chang, B, Smith, JR, Carpten, JD, Stine, OC, Isaacs, SD, Wiley, KE, Henning, L, Ewing, C, Bujnovszky, P, Bleeker, ER, Walsh, PC, Trent, JM, Meyers, DA, Isaacs, WB Linkage of prostate cancer susceptibility loci to chromosome 1. Hum Genet, 108(4), 335-45, 2001.
• Carpten, JD, Makalowska, I, Robbins, CM, Scott, N, Sood, R, Connors, TD, Bonner, TI, Smith, JR, Faruque, MU, Stephan, DA, Pinkett, H, Morgenbesser, SD, Su, K, Graham, C, Gregory, SG, Williams, H, McDonald, L, Baxevanis, AD, Klingler, KW, Landes, GM, Trent, JM A 6-Mb high-resolution physical and transcription map encompassing the hereditary prostate cancer 1 (HPC1) region. Genomics, 64(1), 1-14, 2000.
• Schleutker*, J, Matikainen, M, Smith*, J, Koivisto, P, Baffoe-Bonnie, A, Kainu, T, Gillanders, E, Sankila, R, Pukkala, E, Carpten, J, Stephan, D, Tammela, T, Brownstein, M, Bailey-Wilson, J, Trent, J, Kallioniemi, OP A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease. Clin Cancer Res, 6(12), 4810-5, 2000.
• Bergthorsson, JT, Johannesdottir, G, Arason, A, Benediktsdottir, KR, Agnarsson, BA, Bailey-Wilson, JE, Gillanders, E, Smith, J, Trent, J, Barkardottir, RB Analysis of HPC1, HPCX, and PCaP in Icelandic hereditary prostate cancer. Hum Genet, 107(4), 372-5, 2000.
• Xu, J Combined analysis of hereditary prostate cancer linkage to 1q24-25: results from 772 hereditary prostate cancer families from the International Consortium for Prostate Cancer Genetics. Am J Hum Genet, 66(3), 945-57, 2000.
• Berry*, R, Schaid, DJ, Smith*, JR, French, AJ, Schroeder, JJ, McDonnell, SK, Peterson, BJ, Wang, ZY, Carpten, JD, Roberts, SG, Tester, DJ, Blute, ML, Trent, JM, Thibodeau, SN Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer. Am J Hum Genet, 66(2), 539-46, 2000.
• Gronberg*, H, Smith*, J, Emanuelsson, M, Jonsson, BA, Bergh, A, Carpten, J, Isaacs, W, Xu, J, Meyers, D, Trent, J, Damber, JE In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer. Am J Hum Genet, 65(1), 134-40, 1999.
• Carpten, J., Smith, J., Stephan, D., Isaacs, W., Trent, J "Searching for Prostate Cancer Genes." Science and Medicine, 526-35, 1998.
• Gronberg, H, Isaacs, SD, Smith, JR, Carpten, JD, Bova, GS, Freije, D, Xu, J, Meyers, DA, Collins, FS, Trent, JM, Walsh, PC, Isaacs, WB Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus. JAMA, 278(15), 1251-5, 1997.
• Gronberg, H, Xu, J, Smith, JR, Carpten, JD, Isaacs, SD, Freije, D, Bova, GS, Danber, JE, Bergh, A, Walsh, PC, Collins, FS, Trent, JM, Meyers, DA, Isaacs, WB Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1. Cancer Res, 57(21), 4707-9, 1997.
• Ghosh, S, Karanjawala, ZE, Hauser, ER, Ally, D, Knapp, JI, Rayman, JB, Musick, A, Tannenbaum, J, Te, C, Shapiro, S, Eldridge, W, Musick, T, Martin, C, Smith, JR, Carpten, JD, Brownstein, MJ, Powell, JI, Whiten, R, Chines, P, Nylund, SJ, Magnuson, VL, Boehnke, M, Collins, FS Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group. Genome Res, 7(2), 165-78, 1997.
• Smith, J., Freije, D., Carpten, J., Gronberg, H., Xu, J., Isaacs, S., Brownstein, M., Bova, G., Guo, H., Bujnovszky, P., Nusskern, D., Damber, J., Bergh, A., Emanuelsson, M., Kallioniemi, O., Walker-Daniels, J., Bailey-Wilson, J., Beaty, T., Meyers, D., Walsh, P., Collins, F., Trent, J., and Isaacs, W Major Susceptibility Locus for Prostate Cancer on Chromosome 1 Suggested by a Genome-Wide Search. Science, 274(Nov 22), 1371-1374, 1996.
• Brownstein, M., Carpten, J., and Smith, J Modulation of Nontemplated Nucleotide Addition by Taq DNA Polymerase: Primer Modifications that Facilitate Genotyping. Biotechniques, 201004-1010, 1996.
• Smith, JR, Carpten, JD, Brownstein, MJ, Ghosh, S, Magnuson, VL, Gilbert, DA, Trent, JM, Collins, FS Approach to genotyping errors caused by nontemplated nucleotide addition by Taq DNA polymerase. Genome Res, 5(3), 312-7, 1995.
• Smith, JR, Osborne, TF, Goldstein, JL, Brown, MS Identification of nucleotides responsible for enhancer activity of sterol regulatory element in low density lipoprotein receptor gene. J Biol Chem, 265(4), 2306-10, 1990.
• Gil, G, Smith, JR, Goldstein, JL, Slaughter, CA, Orth, K, Brown, MS, Osborne, TF Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A, 85(23), 8963-7, 1988.
• Smith, JR, Osborne, TF, Brown, MS, Goldstein, JL, Gil, G Multiple sterol regulatory elements in promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A synthase. J Biol Chem, 263(34), 18480-7, 1988.
• Gil, G, Smith, JR, Goldstein, JL, Brown, MS Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters. Proc Natl Acad Sci U S A, 84(7), 1863-6, 1987.