Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.
BACKGROUND
Antioxidants may reduce risk of aggressive prostate cancer, and single-nucleotide polymorphisms (SNP) in antioxidant genes may modify this association.


METHODS
We used Cox proportional hazards regression to examine circulating prediagnostic α-tocopherol, γ-tocopherol, and lycopene; SNPs in SOD2 (n = 5), CAT (n = 6), GPX1 (n = 2), GPX4, (n = 3); and their interactions and risk of lethal prostate cancer among 2,439 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study and Physicians' Health Study.


RESULTS
We observed 223 events over a median follow-up of 10 years. Higher α-tocopherol levels were associated with lower risk of lethal prostate cancer [HR 3rd versus 1st quartile (Q): 0.51; 95% confidence interval (CI), 0.30-0.89; HR 4th versus 1st Q: 0.68; 95% CI, 0.41-1.13; P trend: 0.02]. Men homozygous for the less common allele (G) at rs3746165 in GPX4 had a 35% lower risk of lethal prostate cancer compared with men homozygous for the more common allele (A; HR, 0.65; 95% CI, 0.43-0.99). Among men homozygous for the less common allele in rs3746165, high γ-tocopherol levels were associated with a 3.5-fold increased risk of lethal prostate cancer (95% CI, 1.27-9.72; P value, 0.02; interaction P value, 0.01).


CONCLUSIONS
Among men with nonmetastatic prostate cancer, higher circulating prediagnostic α-tocopherol may be associated with lower risk of developing lethal disease. Variants in GPX4 may be associated with risk of lethal prostate cancer, and may modify the relation between γ-tocopherol and prostate cancer survival.


CONCLUSIONS
Circulating tocopherol levels and variants in GPX4 may affect prostate cancer progression. Cancer Epidemiol Biomarkers Prev; 23(6); 1037-46. ©2014 AACR.
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois erin.vanblarigan@ucsf.edu.
Erin L
EL
Van Blarigan
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Jing
J
Ma
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Stacey A
SA
Kenfield
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Meir J
MJ
Stampfer
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Howard D
HD
Sesso
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Edward L
EL
Giovannucci
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
John S
JS
Witte
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
John W
JW
Erdman
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
June M
JM
Chan
Authors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IllinoisAuthors' Affiliations: Departments of Epidemiology and Biostatistics, Urology, University of California, San Francisco, California; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Epidemiology, and Nutrition, Harvard School of Public Health, Boston, Massachusetts; and Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
Kathryn L
KL
Penney
D000368:Aged; D000975:Antioxidants; D002374:Catalase / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality*; D013482:Superoxide Dismutase / Q000235:genetics; D016019:Survival Analysis; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C577219:CAT protein, human; C000722067:GPX1 protein, human