Pleiotropy between genetic markers of obesity and risk of prostate cancer

Todd L. Edwards, Ayush Giri, Saundra Motley, Wynne Duong, Jay Fowke

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer and genetic markers of obesity and metabolism. Methods: Analyses included 176,520 single-nucleotide polymorphisms (SNP) associated with 23 metabolic traits. We examined the association between SNPs and prostate cancer in 871 cases and 906 controls, including 427 high-grade cases with Gleason >7. Genetic risk scores (GRS) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results: Prostate cancer was associated with five loci, including cyclin M2, with Pvalues less than 1×10-4. In addition, the WHR GRS was associated with high-grade prostate cancer versus controls [OR, 1.05; 95% confidence interval (CI), 1.00-1.11; P=0.048] and high-grade prostate cancer versus low-grade prostate cancer (OR, 1.07; 95% CI, 1.01-1.13; P = 0.03). None of these findings exceeds the threshold for significance after correction for multiple testing. Conclusions: Variants in genes known to be associated with metabolism and obesity may be associated with prostate cancer.Weshow evidence for pleiotropy betweenWHRGRS and prostate cancer grade. This finding is consistent with the function of several WHR genes and previously described relationships with cancer traits. Impact: Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in prostate cancer. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples.

Original languageEnglish (US)
Pages (from-to)1538-1546
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number9
DOIs
StatePublished - Sep 1 2013

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Genetic Markers
Prostatic Neoplasms
Obesity
Waist-Hip Ratio
Single Nucleotide Polymorphism
Body Mass Index
Confidence Intervals
Cyclins
Sample Size
Genes
Prostate
Carcinogenesis
Alleles

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Pleiotropy between genetic markers of obesity and risk of prostate cancer. / Edwards, Todd L.; Giri, Ayush; Motley, Saundra; Duong, Wynne; Fowke, Jay.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 9, 01.09.2013, p. 1538-1546.

Research output: Contribution to journalArticle

Edwards, Todd L. ; Giri, Ayush ; Motley, Saundra ; Duong, Wynne ; Fowke, Jay. / Pleiotropy between genetic markers of obesity and risk of prostate cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 9. pp. 1538-1546.
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abstract = "Background: To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer and genetic markers of obesity and metabolism. Methods: Analyses included 176,520 single-nucleotide polymorphisms (SNP) associated with 23 metabolic traits. We examined the association between SNPs and prostate cancer in 871 cases and 906 controls, including 427 high-grade cases with Gleason >7. Genetic risk scores (GRS) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results: Prostate cancer was associated with five loci, including cyclin M2, with Pvalues less than 1×10-4. In addition, the WHR GRS was associated with high-grade prostate cancer versus controls [OR, 1.05; 95{\%} confidence interval (CI), 1.00-1.11; P=0.048] and high-grade prostate cancer versus low-grade prostate cancer (OR, 1.07; 95{\%} CI, 1.01-1.13; P = 0.03). None of these findings exceeds the threshold for significance after correction for multiple testing. Conclusions: Variants in genes known to be associated with metabolism and obesity may be associated with prostate cancer.Weshow evidence for pleiotropy betweenWHRGRS and prostate cancer grade. This finding is consistent with the function of several WHR genes and previously described relationships with cancer traits. Impact: Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in prostate cancer. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples.",
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AB - Background: To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer and genetic markers of obesity and metabolism. Methods: Analyses included 176,520 single-nucleotide polymorphisms (SNP) associated with 23 metabolic traits. We examined the association between SNPs and prostate cancer in 871 cases and 906 controls, including 427 high-grade cases with Gleason >7. Genetic risk scores (GRS) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results: Prostate cancer was associated with five loci, including cyclin M2, with Pvalues less than 1×10-4. In addition, the WHR GRS was associated with high-grade prostate cancer versus controls [OR, 1.05; 95% confidence interval (CI), 1.00-1.11; P=0.048] and high-grade prostate cancer versus low-grade prostate cancer (OR, 1.07; 95% CI, 1.01-1.13; P = 0.03). None of these findings exceeds the threshold for significance after correction for multiple testing. Conclusions: Variants in genes known to be associated with metabolism and obesity may be associated with prostate cancer.Weshow evidence for pleiotropy betweenWHRGRS and prostate cancer grade. This finding is consistent with the function of several WHR genes and previously described relationships with cancer traits. Impact: Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in prostate cancer. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples.

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