Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

Abstract

Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case-control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377 female breast cancer cases with 377 controls all nested within the prospective 'Diet, Cancer and Health' study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI=1.07-1.92). Pre-diagnostic GPX activity tended to be lower in cases compared with controls. GPX activity was positively correlated with intake of alcohol (P<0.0001) and the catalytic activity was lowered 5% for each additional copy of the variant T-allele (P=0.0003). Alcohol intake was correlated with increased GPX activity for the C-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women.

Epidemiology and Polymorphisms Related to Bladder Cancer in Ecuadorian Individuals

“…It has been determined that individuals who used to smoke are at two times more risk to develop bladder cancer than individuals that never smoke (OR = 2.3; 95% CI 1.28-4.07; p<0.05). These findings are supported because it has previously been reported that smoking results in lower GPX activity (Ravn-Haren, et al, 2006). As a result of the ethnic differences, the distribution of the polymorphisms is affected; some studies have found that the risk of developing bladder cancer when a significant incidence of the L/L allelic variant exists, with the proportion of homozygous individuals for the L/L allele being low for the Asian population and high for the Caucasian population (Ichimura, et al, 2004;Hu & Diamond, 2003).…”

Polymorphisms in Oxidative Stress–Related Genes Are Not Associated with Prostate Cancer Risk in Heavy Smokers

“…In our study, we did not find an overall relationship between GPX1 Pro200Leu polymorphism and prostate cancer. The C allele of GPX1 has been associated with an increased risk of breast (30), bladder (31), and lung cancer (21), but other studies, including breast, have found no associations (32)(33)(34)(35).…”

Oxidative Stress and Oxidative Damage in Carcinogenesis

“…GPX1, the first identified and the most abundant selenoprotein in mammals (Kiss et al 1997), is ubiquitously expressed in humans, protecting cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides (Arthur 2000). A SNP resulting in a proline-leucine substitution at codon 198 of human GPX1 has been identified and has been associated with increased risk of breast (Ravn-Haren et al 2006), prostate (ArsovaSarafinovska et al 2008), lung (Raaschou-Nielsen et al 2007), and bladder cancer (Ichimura et al 2004) but is not consistent in all populations (Ahn et al 2005;Cebrian et al 2006;Udler et al 2007).…”