Cumulative association of five genetic variants with prostate cancer

S. Lilly Zheng; Jielin Sun; Fredrik Wiklund; Shelly Smith; Pär Stattin; Ge Li; Hans Olov Adami; Fang Chi Hsu; Yi Zhu; Katarina Bälter; A. Karim Kader; Aubrey R. Turner; Wennuan Liu; Eugene R. Bleecker; Deborah A. Meyers; David Duggan; John D. Carpten; Bao Li Chang; William B. Isaacs; Jianfeng Xu; Henrik Grönberg

doi:10.1056/NEJMoa075819

Cumulative association of five genetic variants with prostate cancer

S. Lilly Zheng, Jielin Sun, Fredrik Wiklund, Shelly Smith, Pär Stattin, Ge Li, Hans Olov Adami, Fang Chi Hsu, Yi Zhu, Katarina Bälter, A. Karim Kader, Aubrey R. Turner, Wennuan Liu, Eugene R. Bleecker, Deborah A. Meyers, David Duggan, John D. Carpten, Bao Li Chang, William B. Isaacs, Jianfeng XuHenrik Grönberg

School of Medicine

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

523 Scopus citations

Abstract

Background: Single-nucleotide polymorphisms (SNPs) in five chromosomal regions - three at 8q24 and one each at 17q12 and 17q24.3 - have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger. Methods: We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer. Results: Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93×10 ^-28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P = 1.29×10^-8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis. Conclusions: SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.

Original language	English (US)
Pages (from-to)	910-919
Number of pages	10
Journal	New England Journal of Medicine
Volume	358
Issue number	9
DOIs	https://doi.org/10.1056/NEJMoa075819
State	Published - Feb 28 2008

ASJC Scopus subject areas

General Medicine

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Zheng, S. L., Sun, J., Wiklund, F., Smith, S., Stattin, P., Li, G., Adami, H. O., Hsu, F. C., Zhu, Y., Bälter, K., Kader, A. K., Turner, A. R., Liu, W., Bleecker, E. R., Meyers, D. A., Duggan, D., Carpten, J. D., Chang, B. L., Isaacs, W. B., ... Grönberg, H. (2008). Cumulative association of five genetic variants with prostate cancer. New England Journal of Medicine, 358(9), 910-919. https://doi.org/10.1056/NEJMoa075819

Zheng, SL, Sun, J, Wiklund, F, Smith, S, Stattin, P, Li, G, Adami, HO, Hsu, FC, Zhu, Y, Bälter, K, Kader, AK, Turner, AR, Liu, W, Bleecker, ER, Meyers, DA, Duggan, D, Carpten, JD, Chang, BL, Isaacs, WB, Xu, J & Grönberg, H 2008, 'Cumulative association of five genetic variants with prostate cancer', New England Journal of Medicine, vol. 358, no. 9, pp. 910-919. https://doi.org/10.1056/NEJMoa075819

@article{5302cff3d58e4067a764b179712031d5,

title = "Cumulative association of five genetic variants with prostate cancer",

abstract = "Background: Single-nucleotide polymorphisms (SNPs) in five chromosomal regions - three at 8q24 and one each at 17q12 and 17q24.3 - have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger. Methods: We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer. Results: Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93×10 -28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P = 1.29×10-8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis. Conclusions: SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.",

author = "Zheng, {S. Lilly} and Jielin Sun and Fredrik Wiklund and Shelly Smith and P{\"a}r Stattin and Ge Li and Adami, {Hans Olov} and Hsu, {Fang Chi} and Yi Zhu and Katarina B{\"a}lter and Kader, {A. Karim} and Turner, {Aubrey R.} and Wennuan Liu and Bleecker, {Eugene R.} and Meyers, {Deborah A.} and David Duggan and Carpten, {John D.} and Chang, {Bao Li} and Isaacs, {William B.} and Jianfeng Xu and Henrik Gr{\"o}nberg",

year = "2008",

month = feb,

day = "28",

doi = "10.1056/NEJMoa075819",

language = "English (US)",

volume = "358",

pages = "910--919",

journal = "New England Journal of Medicine",

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TY - JOUR

T1 - Cumulative association of five genetic variants with prostate cancer

AU - Zheng, S. Lilly

AU - Sun, Jielin

AU - Wiklund, Fredrik

AU - Smith, Shelly

AU - Stattin, Pär

AU - Li, Ge

AU - Adami, Hans Olov

AU - Hsu, Fang Chi

AU - Zhu, Yi

AU - Bälter, Katarina

AU - Kader, A. Karim

AU - Turner, Aubrey R.

AU - Liu, Wennuan

AU - Bleecker, Eugene R.

AU - Meyers, Deborah A.

AU - Duggan, David

AU - Carpten, John D.

AU - Chang, Bao Li

AU - Isaacs, William B.

AU - Xu, Jianfeng

AU - Grönberg, Henrik

PY - 2008/2/28

Y1 - 2008/2/28

N2 - Background: Single-nucleotide polymorphisms (SNPs) in five chromosomal regions - three at 8q24 and one each at 17q12 and 17q24.3 - have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger. Methods: We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer. Results: Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93×10 -28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P = 1.29×10-8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis. Conclusions: SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.

AB - Background: Single-nucleotide polymorphisms (SNPs) in five chromosomal regions - three at 8q24 and one each at 17q12 and 17q24.3 - have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger. Methods: We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer. Results: Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93×10 -28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P = 1.29×10-8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis. Conclusions: SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.

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U2 - 10.1056/NEJMoa075819

DO - 10.1056/NEJMoa075819

M3 - Article

C2 - 18199855

AN - SCOPUS:40049098166

SN - 0028-4793

VL - 358

SP - 910

EP - 919

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 9

ER -

Cumulative association of five genetic variants with prostate cancer

Abstract

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