A genome-wide pleiotropy scan for prostate cancer risk

Orestis A. Panagiotou, Ruth C. Travis, Daniele Campa, Sonja I. Berndt, Sara Lindstrom, Peter Kraft, Fredrick R. Schumacher, Afshan Siddiq, Stefania I. Papatheodorou, Janet L. Stanford, Demetrius Albanes, Jarmo Virtamo, Stephanie J. Weinstein, W. Ryan Diver, Susan M. Gapstur, Victoria L. Stevens, Heiner Boeing, H. Bas Bueno-De-Mesquita, Aurelio Barricarte Gurrea, Rudolf Kaaks & 19 others Kay Tee Khaw, Vittorio Krogh, Kim Overvad, Elio Riboli, Dimitrios Trichopoulos, Edward Giovannucci, Meir Stampfer, Christopher Haiman, Brian Henderson, Loic Le Marchand, J. Michael Gaziano, David J. Hunter, Stella Koutros, Meredith Yeager, Robert N. Hoover, Stephen J. Chanock, Sholom Wacholder, Timothy J. Key, Konstantinos K. Tsilidis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10-7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p = 3.22 × 10-18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p = 2.5 × 10-6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p = 4.67 × 10;bsupesup it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. Patient summary We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.

Original languageEnglish
Pages (from-to)649-657
Number of pages9
JournalEuropean Urology
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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Prostatic Neoplasms
Genome
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Meta-Analysis
Genome-Wide Association Study
Glycine
Neoplasms

Keywords

  • Aggressive prostate cancer
  • Genome-wide association study
  • Glycine
  • Pleiotropy
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Urology

Cite this

Panagiotou, O. A., Travis, R. C., Campa, D., Berndt, S. I., Lindstrom, S., Kraft, P., ... Tsilidis, K. K. (2015). A genome-wide pleiotropy scan for prostate cancer risk. European Urology, 67(4), 649-657. https://doi.org/10.1016/j.eururo.2014.09.020

A genome-wide pleiotropy scan for prostate cancer risk. / Panagiotou, Orestis A.; Travis, Ruth C.; Campa, Daniele; Berndt, Sonja I.; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R.; Siddiq, Afshan; Papatheodorou, Stefania I.; Stanford, Janet L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J.; Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.; Boeing, Heiner; Bueno-De-Mesquita, H. Bas; Barricarte Gurrea, Aurelio; Kaaks, Rudolf; Khaw, Kay Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J. Michael; Hunter, David J.; Koutros, Stella; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Wacholder, Sholom; Key, Timothy J.; Tsilidis, Konstantinos K.

In: European Urology, Vol. 67, No. 4, 01.04.2015, p. 649-657.

Research output: Contribution to journalArticle

Panagiotou, OA, Travis, RC, Campa, D, Berndt, SI, Lindstrom, S, Kraft, P, Schumacher, FR, Siddiq, A, Papatheodorou, SI, Stanford, JL, Albanes, D, Virtamo, J, Weinstein, SJ, Diver, WR, Gapstur, SM, Stevens, VL, Boeing, H, Bueno-De-Mesquita, HB, Barricarte Gurrea, A, Kaaks, R, Khaw, KT, Krogh, V, Overvad, K, Riboli, E, Trichopoulos, D, Giovannucci, E, Stampfer, M, Haiman, C, Henderson, B, Le Marchand, L, Gaziano, JM, Hunter, DJ, Koutros, S, Yeager, M, Hoover, RN, Chanock, SJ, Wacholder, S, Key, TJ & Tsilidis, KK 2015, 'A genome-wide pleiotropy scan for prostate cancer risk', European Urology, vol. 67, no. 4, pp. 649-657. https://doi.org/10.1016/j.eururo.2014.09.020
Panagiotou OA, Travis RC, Campa D, Berndt SI, Lindstrom S, Kraft P et al. A genome-wide pleiotropy scan for prostate cancer risk. European Urology. 2015 Apr 1;67(4):649-657. https://doi.org/10.1016/j.eururo.2014.09.020
Panagiotou, Orestis A. ; Travis, Ruth C. ; Campa, Daniele ; Berndt, Sonja I. ; Lindstrom, Sara ; Kraft, Peter ; Schumacher, Fredrick R. ; Siddiq, Afshan ; Papatheodorou, Stefania I. ; Stanford, Janet L. ; Albanes, Demetrius ; Virtamo, Jarmo ; Weinstein, Stephanie J. ; Diver, W. Ryan ; Gapstur, Susan M. ; Stevens, Victoria L. ; Boeing, Heiner ; Bueno-De-Mesquita, H. Bas ; Barricarte Gurrea, Aurelio ; Kaaks, Rudolf ; Khaw, Kay Tee ; Krogh, Vittorio ; Overvad, Kim ; Riboli, Elio ; Trichopoulos, Dimitrios ; Giovannucci, Edward ; Stampfer, Meir ; Haiman, Christopher ; Henderson, Brian ; Le Marchand, Loic ; Gaziano, J. Michael ; Hunter, David J. ; Koutros, Stella ; Yeager, Meredith ; Hoover, Robert N. ; Chanock, Stephen J. ; Wacholder, Sholom ; Key, Timothy J. ; Tsilidis, Konstantinos K. / A genome-wide pleiotropy scan for prostate cancer risk. In: European Urology. 2015 ; Vol. 67, No. 4. pp. 649-657.
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abstract = "Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10-7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95{\%} confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95{\%} CI 1.16-1.27; p = 3.22 × 10-18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95{\%} CI 0.86-0.94; p = 2.5 × 10-6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95{\%} CI 1.06-1.19; p = 4.67 × 10;bsupesup it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. Patient summary We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.",
keywords = "Aggressive prostate cancer, Genome-wide association study, Glycine, Pleiotropy, Single-nucleotide polymorphism",
author = "Panagiotou, {Orestis A.} and Travis, {Ruth C.} and Daniele Campa and Berndt, {Sonja I.} and Sara Lindstrom and Peter Kraft and Schumacher, {Fredrick R.} and Afshan Siddiq and Papatheodorou, {Stefania I.} and Stanford, {Janet L.} and Demetrius Albanes and Jarmo Virtamo and Weinstein, {Stephanie J.} and Diver, {W. Ryan} and Gapstur, {Susan M.} and Stevens, {Victoria L.} and Heiner Boeing and Bueno-De-Mesquita, {H. Bas} and {Barricarte Gurrea}, Aurelio and Rudolf Kaaks and Khaw, {Kay Tee} and Vittorio Krogh and Kim Overvad and Elio Riboli and Dimitrios Trichopoulos and Edward Giovannucci and Meir Stampfer and Christopher Haiman and Brian Henderson and {Le Marchand}, Loic and Gaziano, {J. Michael} and Hunter, {David J.} and Stella Koutros and Meredith Yeager and Hoover, {Robert N.} and Chanock, {Stephen J.} and Sholom Wacholder and Key, {Timothy J.} and Tsilidis, {Konstantinos K.}",
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TY - JOUR

T1 - A genome-wide pleiotropy scan for prostate cancer risk

AU - Panagiotou, Orestis A.

AU - Travis, Ruth C.

AU - Campa, Daniele

AU - Berndt, Sonja I.

AU - Lindstrom, Sara

AU - Kraft, Peter

AU - Schumacher, Fredrick R.

AU - Siddiq, Afshan

AU - Papatheodorou, Stefania I.

AU - Stanford, Janet L.

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie J.

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Stevens, Victoria L.

AU - Boeing, Heiner

AU - Bueno-De-Mesquita, H. Bas

AU - Barricarte Gurrea, Aurelio

AU - Kaaks, Rudolf

AU - Khaw, Kay Tee

AU - Krogh, Vittorio

AU - Overvad, Kim

AU - Riboli, Elio

AU - Trichopoulos, Dimitrios

AU - Giovannucci, Edward

AU - Stampfer, Meir

AU - Haiman, Christopher

AU - Henderson, Brian

AU - Le Marchand, Loic

AU - Gaziano, J. Michael

AU - Hunter, David J.

AU - Koutros, Stella

AU - Yeager, Meredith

AU - Hoover, Robert N.

AU - Chanock, Stephen J.

AU - Wacholder, Sholom

AU - Key, Timothy J.

AU - Tsilidis, Konstantinos K.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10-7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p = 3.22 × 10-18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p = 2.5 × 10-6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p = 4.67 × 10;bsupesup it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. Patient summary We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.

AB - Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10-7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p = 3.22 × 10-18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p = 2.5 × 10-6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p = 4.67 × 10;bsupesup it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. Patient summary We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.

KW - Aggressive prostate cancer

KW - Genome-wide association study

KW - Glycine

KW - Pleiotropy

KW - Single-nucleotide polymorphism

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