Association between single nucleotide polymorphisms in the antioxidant genes CAT, GR and SOD1, erythrocyte enzyme activities, dietary and life style factors and breast cancer risk in a Danish, prospective cohort study

Tine Iskov Kopp,Lars Ove Dragsted,Ulla Vogel,Anne Tjonneland,Gitte Ravn-Haren

doi:10.18632/oncotarget.18062

Abstract

Exposure to estrogens and alcohol consumption - the two only well-established risk factors for breast cancer - are capable of causing oxidative stress, which has been linked to progression of breast cancer. Here, five functional polymorphisms in the antioxidant genes SOD1, CAT and GSR were investigated in 703 breast cancer case-control pairs in the Danish, prospective “Diet, Cancer and Health” cohort together with gene-environment interactions between the polymorphisms, enzyme activities and intake of fruits and vegetables, alcohol and smoking in relation to breast cancer risk. Our results showed that genetically determined variations in the antioxidant enzyme activities of SOD1, CAT and GSR were not associated with risk of breast cancer per se. However, intake of alcohol, fruit and vegetables, and smoking status interacted with some of the polymorphisms in relation to breast cancer risk. Four polymorphisms were strongly associated with enzyme activity, but there was no interaction between any of the studied environmental factors and the polymorphisms in relation to enzyme activity. Additionally, single measurement of enzyme activity at entry to the cohort was not associated with risk of breast cancer. Our results therefore suggest that the antioxidant enzyme activities studied here are not major determinants of breast cancer risk.

Highlights

Breast cancer (BC) is the most common type of cancer in Denmark among women and the second leading cause of cancer death after lung cancer [1]
Carriage of the variant G-allele of SOD1/ rs202445 was associated with a 13% increased risk of BC, whereas wild-type AA-carriers showed no modified risk of BC per 100 g fruits and vegetables per day (Table 4)
We found that genetically determined variations in the antioxidant enzyme activities of CAT, GSR and SOD1 were not associated with risk of BC per se in this relatively large cohort

Summary

Introduction

Breast cancer (BC) is the most common type of cancer in Denmark among women and the second leading cause of cancer death after lung cancer [1]. Several studies have indicated that an increased intake of fruits and vegetables may affect the enzymatic antioxidant defense system, leading to increased enzyme activities [21,22,23,24] These dietary and life style choices may modulate risk of BC by altering the level of oxidative stress, such that alcohol consumption and smoking increase the risk, while intake of fruit and vegetables decreases the risk. Genetically determined variations in the activities of enzymes that protect against or generate oxidative stress could modify associations between dietary antioxidants and exogenous sources of ROS, and BC risk, and explain some of the inconsistencies in the results from these studies. Prospective cohort studies may reveal whether these lowered activities are a cause or consequence of the disease in combination with examination of dietary and life style factors and their interaction with the enzymes in relation to risk of disease

Methods

Results

Conclusion