TY - JOUR
T1 - Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer
AU - Olson, S. H.
AU - Carlson, M. D.A.
AU - Ostrer, H.
AU - Harlap, S.
AU - Stone, A.
AU - Winters, M.
AU - Ambrosone, C. B.
N1 - Funding Information:
This study supported by National Cancer Institute Awards R01CA61088 (S. Harlap) and R03CA72456 (S.H. Olson). The authors thank Patricia A. Thompson for her contributions.
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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U2 - 10.1016/j.ygyno.2004.03.027
DO - 10.1016/j.ygyno.2004.03.027
M3 - Article
C2 - 15196853
AN - SCOPUS:2942668384
SN - 0090-8258
VL - 93
SP - 615
EP - 620
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -
