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

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

Research output: Contribution to journalArticle

Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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. DISCUSSION. 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.

Original languageEnglish (US)
Pages (from-to)1257-1262
Number of pages6
JournalProstate
Volume68
Issue number12
DOIs
StatePublished - Sep 1 2008

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Prostatic Neoplasms
Population
Odds Ratio
Genetic Predisposition to Disease
Genetic Markers
Single Nucleotide Polymorphism
Cancer Care Facilities
National Cancer Institute (U.S.)
Case-Control Studies
Neoplasms

Keywords

  • 17q12
  • 17q24.3
  • 8q24
  • Association
  • Interaction

ASJC Scopus subject areas

  • Urology

Cite this

Sun, J., Chang, B. L., Isaacs, S. D., Wiley, K. E., Wiklund, F., Stattin, P., ... Zheng, S. L. (2008). Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations. Prostate, 68(12), 1257-1262. https://doi.org/10.1002/pros.20793

Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations. / Sun, Jielin; Chang, Bao Li; Isaacs, Sarah D.; Wiley, Kathleen E.; Wiklund, Fredrik; Stattin, Pär; Duggan, David; Carpten, John D.; Trock, Bruce; Partin, Alan Wayne; Walsh, Patrick; Grönberg, Henrik; Xu, Jianfeng; Isaacs, William B; Zheng, S. Lilly.

In: Prostate, Vol. 68, No. 12, 01.09.2008, p. 1257-1262.

Research output: Contribution to journalArticle

Sun, J, Chang, BL, Isaacs, SD, Wiley, KE, Wiklund, F, Stattin, P, Duggan, D, Carpten, JD, Trock, B, Partin, AW, Walsh, P, Grönberg, H, Xu, J, Isaacs, WB & Zheng, SL 2008, 'Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations', Prostate, vol. 68, no. 12, pp. 1257-1262. https://doi.org/10.1002/pros.20793
Sun J, Chang BL, Isaacs SD, Wiley KE, Wiklund F, Stattin P et al. Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations. Prostate. 2008 Sep 1;68(12):1257-1262. https://doi.org/10.1002/pros.20793
Sun, Jielin ; Chang, Bao Li ; Isaacs, Sarah D. ; Wiley, Kathleen E. ; Wiklund, Fredrik ; Stattin, Pär ; Duggan, David ; Carpten, John D. ; Trock, Bruce ; Partin, Alan Wayne ; Walsh, Patrick ; Grönberg, Henrik ; Xu, Jianfeng ; Isaacs, William B ; Zheng, S. Lilly. / Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations. In: Prostate. 2008 ; Vol. 68, No. 12. pp. 1257-1262.
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abstract = "BACKGROUND. 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. METHODS. 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. RESULTS. 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. DISCUSSION. 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.",
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AU - Stattin, Pär

AU - Duggan, David

AU - Carpten, John D.

AU - Trock, Bruce

AU - Partin, Alan Wayne

AU - Walsh, Patrick

AU - Grönberg, Henrik

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AU - Isaacs, William B

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N2 - BACKGROUND. 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. METHODS. 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. RESULTS. 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. DISCUSSION. 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.

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