Elsevier

Gynecologic Oncology

Volume 107, Issue 3, December 2007, Pages 388-391
Gynecologic Oncology

Rapid Communication
The MnSOD Val9Ala polymorphism, dietary antioxidant intake, risk and survival in ovarian cancer (Australia)

https://doi.org/10.1016/j.ygyno.2007.09.004Get rights and content

Abstract

Objective.

We assessed the MnSOD Val9Ala polymorphism and its interaction with dietary antioxidant intake in ovarian cancer risk and survival.

Methods.

The MnSOD polymorphism was assessed in 543 ovarian cancer cases and 1130 controls. We used regression analysis to model the association between genotype and risk, case-only analyses to estimate risk modification by dietary variables, and proportional hazard models for survival analysis.

Results.

We found no association between this polymorphism and ovarian cancer risk or survival, nor was there evidence of any interaction with dietary antioxidant intake.

Conclusion.

The Val9Ala MnSOD polymorphism does not influence ovarian cancer risk or survival.

Introduction

Manganese superoxide dismutase (MnSOD) is a mitochondrial matrix enzyme that scavenges reactive oxygen species (ROS) and protects the cell against the insults of oxidative stress [1]. Transgenic animal studies demonstrating increased tumor incidence associated with reduced MnSOD activity, and diminished antioxidant enzyme levels in cancer cells and tumors, implicate MnSOD as a tumor suppressor gene [2], [3]. One hypothesis for ovarian carcinogenesis is that rapid cell division of the ovarian epithelium, and the inflammatory processes associated with ovulation may lead to the production of ROS, resulting in oxidative damage to DNA [4]. The valine variant of the Valine–9Alanine polymorphism is the result of a T  C substitution at position − 9 of the mitochondrial targeting sequence (MTS), the signal peptide necessary for transport of MnSOD from the cytosol into the mitochondrion. This variant is predicted to alter protein conformation, and is believed to compromise transport and localization of MnSOD, leaving the cell vulnerable to oxidative damage [5]. One hospital-based case–control study of 125 ovarian cancer cases and 193 controls reported a twofold increased risk among carriers of one or two alanine alleles compared to valine homozygotes [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1–4.0] [6]. We report the results of risk and survival analyses associated with the MnSOD Val9Ala polymorphism in a large Australian ovarian cancer case–control study, as well as case-only analyses to estimate possible risk modification by dietary antioxidant intake.

Section snippets

Materials and methods

Approval for this study was obtained from the ethics committees of the University of Queensland, University of Melbourne, Queensland Institute of Medical Research, Queensland Cancer Fund, New South Wales Cancer Council, Cancer Council Victoria, National Death Index and all metropolitan hospitals where patients were recruited.

We analyzed data from 543 women with epithelial ovarian cancer, with tumor histology as follows: 320 (59.0%) serous, 68 (12.5%) mucinous, 62 (11.4%) endometrioid, 32 (5.9%)

Results

The distribution of Val9Ala genotypes in the combined group of controls was in Hardy–Weinberg equilibrium (p > 0.2). Multivariate analysis showed no significant association between the Val9Ala polymorphism and ovarian cancer (Table 2). Further adjustment for oral contraceptive use in the subset of women with this information available did not appreciably alter the odds ratio, nor did restricting analyses to serous cases only (data not shown). Case-only analysis of genotype-by-nutrient interaction

Discussion

Our study is the first to investigate the role of the MnSOD Val9Ala polymorphism and its interaction with dietary antioxidants in ovarian cancer risk and survival. The results of Val9Ala association studies and cancer risk have been inconsistent, with the alanine allele associated with an increased risk of breast cancer [12] and prostrate cancer [13] in some studies, and a decreased risk of breast cancer [14] and lung cancer [15] in others. In vitro and animal studies [16], as well as

Acknowledgments

This work was supported by grants from the National Health and Medical Research Council of Australia, Queensland Cancer Fund, Mayne Bequest Fund, University of Queensland. A. Spurdle and G. Chenevix-Trench are supported by fellowships from the National Health and Medical Research Council and P. Webb is supported by The Cancer Council Queensland. We thank the women who participated in this research, and the physicians, surgeons and oncologists who endorsed this study; John Hopper, Margaret

References (20)

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