title: Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.
abstract: BACKGROUND
  Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers.
  
  
  OBJECTIVE
  To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability.
  
  
  METHODS
  We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression.
  
  
  RESULTS
  Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P < 0.001). Among men with Gleason score ≤ 3 + 4, higher lycopene levels were associated with lower FGA (P = 0.04).
  
  
  CONCLUSIONS
  Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of prostate cancer early in its natural history.
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.|Department of Epidemiology and Biostatistics, University of California, San Francisco, California.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Nordström
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.|Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Van Blarigan
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.
authors.forename: Vy
authors.initials: V
authors.lastname: Ngo
authors.affiliation: Computational Biology Core, Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.affiliation: Biostatistics Core, Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.|Department of Pathology, University of California, San Francisco, California.
authors.forename: Jeffry
authors.initials: J
authors.lastname: Simko
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.|Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Research Center, University of California, San Francisco, California.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Paris
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000032:analysis; D002338:Carotenoids / Q000097:blood* / Q000235:genetics*; D003430:Cross-Sectional Studies; D004260:DNA Repair / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000077276:Lycopene; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics; D019207:beta Carotene / Q000097:blood
chemical_list: D000975:Antioxidants; D019207:beta Carotene; D002338:Carotenoids; C041635:alpha-carotene; D013482:Superoxide Dismutase; D000077276:Lycopene
keywords: carotenes; genetic polymorphisms; genomic instability; lycopene; prostate cancer