Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer

S. H. Olson, M. D A Carlson, Harry Ostrer, S. Harlap, A. Stone, M. Winters, C. B. Ambrosone

Research output: Contribution to journalArticle

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Abstract

Objective. One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. Methods. In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T→C (val→ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G→A substitution at the -463 position in the promoter region of MPO; and (3) the C→T (pro→ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. Results. For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). Conclusions. While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)615-620
Number of pages6
JournalGynecologic Oncology
Volume93
Issue number3
DOIs
StatePublished - Jun 2004
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Peroxidase
Odds Ratio
Oxidative Stress
Genotype
Confidence Intervals
Genes
Inflammation
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Oral Contraceptives
Protein Sorting Signals
Ovulation
Parity
Genetic Promoter Regions
NAD
Superoxide Dismutase
Electrophoresis
Case-Control Studies
Exons
Mass Spectrometry

Keywords

  • Genetic polymorphisms
  • Manganese superoxide dismutase
  • Myeloperoxidase
  • NAD(P)H:oxidoreductase 1
  • Ovarian carcinoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Olson, S. H., Carlson, M. D. A., Ostrer, H., Harlap, S., Stone, A., Winters, M., & Ambrosone, C. B. (2004). Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer. Gynecologic Oncology, 93(3), 615-620. https://doi.org/10.1016/j.ygyno.2004.03.027

Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer. / Olson, S. H.; Carlson, M. D A; Ostrer, Harry; Harlap, S.; Stone, A.; Winters, M.; Ambrosone, C. B.

In: Gynecologic Oncology, Vol. 93, No. 3, 06.2004, p. 615-620.

Research output: Contribution to journalArticle

Olson, SH, Carlson, MDA, Ostrer, H, Harlap, S, Stone, A, Winters, M & Ambrosone, CB 2004, 'Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer', Gynecologic Oncology, vol. 93, no. 3, pp. 615-620. https://doi.org/10.1016/j.ygyno.2004.03.027
Olson, S. H. ; Carlson, M. D A ; Ostrer, Harry ; Harlap, S. ; Stone, A. ; Winters, M. ; Ambrosone, C. B. / Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer. In: Gynecologic Oncology. 2004 ; Vol. 93, No. 3. pp. 615-620.
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abstract = "Objective. One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. Methods. In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T→C (val→ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G→A substitution at the -463 position in the promoter region of MPO; and (3) the C→T (pro→ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. Results. For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95{\%} confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95{\%} CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95{\%} CI 0.69-7.6). Conclusions. While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.",
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T1 - Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer

AU - Olson, S. H.

AU - Carlson, M. D A

AU - Ostrer, Harry

AU - Harlap, S.

AU - Stone, A.

AU - Winters, M.

AU - Ambrosone, C. B.

PY - 2004/6

Y1 - 2004/6

N2 - Objective. One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. Methods. In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T→C (val→ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G→A substitution at the -463 position in the promoter region of MPO; and (3) the C→T (pro→ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. Results. For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). Conclusions. While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.

AB - Objective. One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. Methods. In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T→C (val→ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G→A substitution at the -463 position in the promoter region of MPO; and (3) the C→T (pro→ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. Results. For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). Conclusions. While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.

KW - Genetic polymorphisms

KW - Manganese superoxide dismutase

KW - Myeloperoxidase

KW - NAD(P)H:oxidoreductase 1

KW - Ovarian carcinoma

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