Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP

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

doi:10.1093/jnci/djm250

Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP

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

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.

Original language	English (US)
Pages (from-to)	1836-1844
Number of pages	9
Journal	Journal of the National Cancer Institute
Volume	99
Issue number	24
DOIs	https://doi.org/10.1093/jnci/djm250
State	Published - Dec 2007

ASJC Scopus subject areas

Oncology
Cancer Research

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Duggan, D., Zheng, S. L., Knowlton, M., Benitez, D., Dimitrov, L., Wiklund, F., Robbins, C., Isaacs, S. D., Cheng, Y., Li, G., Sun, J., Chang, B. L., Marovich, L., Wiley, K. E., Bälter, K., Stattin, P., Adami, H. O., Gielzak, M., Yan, G., ... Carpten, J. D. (2007). Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP. Journal of the National Cancer Institute, 99(24), 1836-1844. https://doi.org/10.1093/jnci/djm250

Duggan, D, Zheng, SL, Knowlton, M, Benitez, D, Dimitrov, L, Wiklund, F, Robbins, C, Isaacs, SD, Cheng, Y, Li, G, Sun, J, Chang, BL, Marovich, L, Wiley, KE, Bälter, K, Stattin, P, Adami, HO, Gielzak, M, Yan, G, Sauvageot, J, Liu, W, Kim, JW, Bleecker, ER, Meyers, DA, Trock, BJ, Partin, AW, Walsh, PC , Isaacs, WB, Grönberg, H, Xu, J & Carpten, JD 2007, 'Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP', Journal of the National Cancer Institute, vol. 99, no. 24, pp. 1836-1844. https://doi.org/10.1093/jnci/djm250

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title = "Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP",

abstract = "Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.",

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

year = "2007",

month = dec,

doi = "10.1093/jnci/djm250",

language = "English (US)",

volume = "99",

pages = "1836--1844",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "24",

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TY - JOUR

T1 - Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP

AU - Duggan, David

AU - Zheng, Siqun L.

AU - Knowlton, Michele

AU - Benitez, Debbie

AU - Dimitrov, Latchezar

AU - Wiklund, Fredrik

AU - Robbins, Christiane

AU - Isaacs, Sarah D.

AU - Cheng, Yu

AU - Li, Ge

AU - Sun, Jielin

AU - Chang, Bao Li

AU - Marovich, Leslie

AU - Wiley, Kathleen E.

AU - Bälter, Katarina

AU - Stattin, Pär

AU - Adami, Hans Olov

AU - Gielzak, Marta

AU - Yan, Guifang

AU - Sauvageot, Jurga

AU - Liu, Wennuan

AU - Kim, Jin Woo

AU - Bleecker, Eugene R.

AU - Meyers, Deborah A.

AU - Trock, Bruce J.

AU - Partin, Alan W.

AU - Walsh, Patrick C.

AU - Isaacs, William B.

AU - Grönberg, Henrik

AU - Xu, Jianfeng

AU - Carpten, John D.

PY - 2007/12

Y1 - 2007/12

N2 - Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.

AB - Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.

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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP

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