Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes

Abstract

The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.

Genetic variation in the androgen estrogen conversion pathway in relation to breast cancer prognosticators

“…Breast cancer is believed to be induced by excessive estrogen exposure and genetic variation in genes involved in the estrogen metabolism pathway is therefore likely to be important for the disease. Numerous genetic association studies addressing association with cancer risk and genes in the estrogen metabolism pathway have been reported with conflicting results, probably reflecting the low penetrance of mutations in genes within the estrogen metabolism pathway, suboptimal study designs, underpowered studies or a combination of these factors [1][2][3]. We have recently been able to show, using a pathway approach, that there is an association between breast cancer risk and some of the genes involved in the androgen-to-estrogen conversion pathway (a sub-pathway of the complete estrogen metabolism pathway), particularly for the risk of estrogen receptor(ER)-positive tumours [4].…”

Glutathione S-transferase P1 Ile105Val polymorphism and breast cancer risk: convergence and divergence of the two recent meta-analyses

“…Specifically, the data reported by Lu et al [1] for the studies by Maugard et al [5], Krajinovic et al [6], Unlu et al [7] and Torresan et al [8] do not seem in line with the data provided in the original publications. The genotype frequencies for Ile/Ile, Ile/Val, Val/Val in cases and controls should read: 99-101-20-81-90-25 for the study by Maugard et al [5], 69-55-5-91-73-13 for the study by Krajinovic et al [6], 28-26-11-51-37-20 for the study by Unlu et al [7] and 54-35-13-77-22-3 for the study by Torresan et al [8] (italics denote the discrepancies between Lu et al [1] and the original publications). The above may imply that the original odds ratios for the aforementioned studies may significantly differ from those calculated by Lu et al [1].…”

“…should be 54-35-13-77-22-3 for the study by Torresan et al [8] However, the HWE in controls calculated based on Dr.…”

Genetic Variants of CYP2D6 Gene and Cancer Risk: A HuGE Systematic Review and Meta-analysis

“…According to the inclusion criteria, 43 studies (Agúndez et al, 1994;Wundrack et al, 1994;Agúndez et al, 1996;Ladona et al1996;Legrand et al, 1996;London et al, 1997;Agúndez et al, 1998;Febbo et al, 1998; González et al, 1998; Hu et Shaw et al, 1998;Krajinovic et al, 1999;Lemos et al, 1999;Topić et al, 2000;Butler et al, 2001;Liu et al, 2002;Sobti et al, 2003;Chen et al, 2004;Fukatsu et al, 2004;Li et al, 2004;Gajecka et al, 2005;Gomes et al, 2005;Guo et al, 2005;Liang et al, 2005;Mochizuki et al, 2005;Sobti et al, 2005;Aydin-Sayitoglu et al, 2006;Bonanni et al, 2006;Li et al, 2006;Lemos et al, 2007;Chen et al, 2008;Khedhaier et al, 2008;Majumdar et al, 2008;Ouerhani et al, 2008 ;Torresan et al, 2008;Yan et al, 2008;Altayli et al, 2009;Gutman et al, 2009;Lim et al, 2011;Luo et al, 2011;Zhou et al, 2011) appeared to have met the inclusion criteria and were subjected to further examination. The flow chart of study selection is shown...…”