Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis

Abstract

Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions; cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in the metabolism of a vast number of xenobiotics, as well as endogenous substrates. Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their potential implication in terms of breast cancer risk: T3801C, T3205C, A2455G (Ile462Val), and C2453A (Thr461Asp); controversy exists regarding their role. This meta-analysis aims to examine whether the four aforementioned polymorphisms are associated with breast cancer risk. Separate analyses were performed on Caucasian, Chinese, and African populations, as well as on premenopausal and postmenopausal women. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to October 2009. Concerning T3801C, 32 studies were eligible (11,909 cases and 16,179 controls), 29 studies (12,257 cases and 20,379 controls) were eligible for A2455G, 11 studies (7,189 cases and 8,491 controls) were eligible for C2453A, and eight studies were eligible for T3205C (1,378 cases and 1,642 controls). Pooled odds ratios (OR) were appropriately derived from fixed-or random-effect models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Homozygous subjects of Caucasian origin carrying the A2455G G allele exhibited elevated breast cancer risk (pooled OR = 2.185, 95% CI 1.253-3.808, fixed effects), whereas heterozygous carriers did not (pooled OR = 1.062, 95% CI 0.852-1.323, random effects). A2455G polymorphism status was not associated with breast cancer risk in Chinese subjects or specifically in premenopausal/postmenopausal women. T3801C, T3205C, and C2453A status were not associated with breast cancer risk at any analysis. In conclusion, this meta-analysis points to the A2455G G allele as a risk factor for breast cancer among Caucasian subjects. On the contrary, T3801C, T3205C, and C2453A status does not seem capable of modifying breast cancer risk.

Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis

“…P450 polymorphisms may well exhibit race-specific effects [1,12]. As a result, given that the vast majority of data came from Caucasian populations in this meta-analysis, the results may not be safely extrapolated upon Chinese subjects.…”

“…homozygous carriers versus 'wild type' and heterozygous carriers grouped together. Separate racespecific analyses were considered in case relevant data existed, according to the algorithm adopted in our previous meta-analyses [10][11][12][13][14]. In case of zero cells, an appropriate continuity correction (addition of 0.5) was implemented [10].…”

CYP1A1 Gene Polymorphism and Breast Cancer

“…It is assumed that some genetic polymorphisms might modify the risk of breast cancer by influencing the CYP1A1 enzyme activity (6). Four single nucleotide polymorphisms in CYP1A1 have been identified, including T3801C, T3205C, A2455G (Ile462Val), and C2453A (Thr461Asp) (7). In the present work, the association between breast cancer and CYP1A1 Thr461Asn polymorphism was investigated.…”

Are pharmacogenomic biomarkers an effective tool to predict taxane toxicity and outcome in breast cancer patients? Literature review

“…The impact of genetic variants on taxane response is unclear: Several studies did not find any relationship between taxane-related gene polymorphisms and response, while others did [54,55], and the most studied genes have been CYP3A4, CYP2C8 and ABCB1 [56][57][58][59]. Recently, new genome-wide association studies (GWAS) have been reported, searching to correlate data of taxane pharmacogenomics with toxicity [60]; this method enables the simultaneous view on a huge amount of known genetic variation in humans, such as the case of the polymorphism CYP1A1 rs1048943 A/G, in association with the risk of development of breast cancer [61]. No GWAS on taxane outcomes and breast cancer has been published since now.…”