Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence

Paul J. Dluzniewski, Ming Hsi Wang, Siqun Lilly Zheng, Angelo M. De Marzo, Charles G. Drake, Helen L. Fedor, Alan W. Partin, Misop Han, M. Daniele Fallin, Jianfeng Xu, William B. Isaacs, Elizabeth A. Platz

Research output: Contribution to journalArticle

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Abstract

Background: To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods: We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR , IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95% confidence intervals (CI). Results: The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95% CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI: 0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence. Conclusion: Variation in IL10, CRP, GSTP1, IL1B , and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors. Impact: This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis.

Original languageEnglish (US)
Pages (from-to)1774-1782
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Interleukin-10
Prostatic Neoplasms
Recurrence
Genes
Single Nucleotide Polymorphism
Confidence Intervals
Haplotypes
Interleukin-6
Alleles
Prostatectomy
Interleukin-8
Paraffin
DNA Damage
Case-Control Studies
Reactive Oxygen Species
Logistic Models
Lymph Nodes
DNA

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Dluzniewski, P. J., Wang, M. H., Zheng, S. L., De Marzo, A. M., Drake, C. G., Fedor, H. L., ... Platz, E. A. (2012). Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence. Cancer Epidemiology Biomarkers and Prevention, 21(10), 1774-1782. https://doi.org/10.1158/1055-9965.EPI-12-0458

Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence. / Dluzniewski, Paul J.; Wang, Ming Hsi; Zheng, Siqun Lilly; De Marzo, Angelo M.; Drake, Charles G.; Fedor, Helen L.; Partin, Alan W.; Han, Misop; Fallin, M. Daniele; Xu, Jianfeng; Isaacs, William B.; Platz, Elizabeth A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 10, 10.2012, p. 1774-1782.

Research output: Contribution to journalArticle

Dluzniewski, PJ, Wang, MH, Zheng, SL, De Marzo, AM, Drake, CG, Fedor, HL, Partin, AW, Han, M, Fallin, MD, Xu, J, Isaacs, WB & Platz, EA 2012, 'Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 10, pp. 1774-1782. https://doi.org/10.1158/1055-9965.EPI-12-0458
Dluzniewski, Paul J. ; Wang, Ming Hsi ; Zheng, Siqun Lilly ; De Marzo, Angelo M. ; Drake, Charles G. ; Fedor, Helen L. ; Partin, Alan W. ; Han, Misop ; Fallin, M. Daniele ; Xu, Jianfeng ; Isaacs, William B. ; Platz, Elizabeth A. / Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 10. pp. 1774-1782.
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abstract = "Background: To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods: We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR , IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95{\%} confidence intervals (CI). Results: The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95{\%} CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95{\%} CI: 0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence. Conclusion: Variation in IL10, CRP, GSTP1, IL1B , and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors. Impact: This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis.",
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T1 - Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence

AU - Dluzniewski, Paul J.

AU - Wang, Ming Hsi

AU - Zheng, Siqun Lilly

AU - De Marzo, Angelo M.

AU - Drake, Charles G.

AU - Fedor, Helen L.

AU - Partin, Alan W.

AU - Han, Misop

AU - Fallin, M. Daniele

AU - Xu, Jianfeng

AU - Isaacs, William B.

AU - Platz, Elizabeth A.

PY - 2012/10

Y1 - 2012/10

N2 - Background: To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods: We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR , IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95% confidence intervals (CI). Results: The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95% CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI: 0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence. Conclusion: Variation in IL10, CRP, GSTP1, IL1B , and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors. Impact: This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis.

AB - Background: To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer. Methods: We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR , IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95% confidence intervals (CI). Results: The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95% CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI: 0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence. Conclusion: Variation in IL10, CRP, GSTP1, IL1B , and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors. Impact: This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis.

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