Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Abstract

ABSTRACT. Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which significantly promote proliferation of cancer cells in vitro and in vivo. We looked for a possible association between human CYP2C19*3 gene polymorphism and breast cancer in the Chinese Han population. In a Chinese Han case-control study of breast cancer patients (N = 600) and age-and gender-matched healthy controls (N = 600), we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in breast cancer patients than in control subjects (6.67 vs 3.00%; P = 0.003). The odds ratio for carriers of AG + AA genotype for breast cancer was 2.31 (95% confidence interval = 1.27-4.43). Among patients, estrogen receptor, tumor size, histologic grade, presence of primary lymphonode metastases, progesterone receptor positivity, and age at diagnosis were not found to be significantly associated with CYP2C19*3 genotypes (all P > 0.05). We conclude that the CYP2C19*3 gene polymorphism is associated with breast cancer risk in Chinese Han women.

Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

“…The CYP2C9*2 allele has not been detected in a Chinese population, and the frequency of the CYP2C9 * 3 allele was 2–2.6% [22,24]. The CYP2C19*2 mutant allele was found at a frequency of 21.9% in this study, which is not significantly different from previous reports in the literature for Caucasians (15 20%) [1,7] and Japanese (26.7%) [25].…”

Physical Confirmation and Comparative Genomics of the RatMammary carcinoma susceptibility 3Quantitative Trait Locus

“…Rat Mcs3 was found to contain sequence orthologous to human 11q13/14 , which contains multiple genes and is amplified in a subset of female breast carcinomas with poor prognosis (Tsuda et al 1989). In addition to a functional correlation with breast cancer development, studies reporting genetic associations of CYP2C19 variants with breast cancer susceptibility have been published (Justenhoven et al 2009; Sangrajrang et al 2009; Gan et al 2011). …”

“…There is evidence that the CYP2C19*3 variant may be associated with breast cancer risk in Chinese Han women (Gan et al 2011). Neither the CYP2C19*17 variant, which results in a rapid metabolizer phenotype, nor the CYP2C19*2 variant were associated with breast cancer risk in population-based studies of women of European descent; however, CYP2C19*17 was associated with decreased risk in women using hormone replacement therapy for >10 yr (Justenhoven et al 2009, 2012; MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk 2010).…”

Polymorphisms of Phase I and Phase II Enzymes and Breast Cancer Risk

“…It has been shown that functional genetic variants of the CYP2C19 are associated with overall breast cancer risk and HRT-related breast cancer risk (Gan et al, 2011; Justenhoven et al, 2012). It is of note that these findings in two independent studies show similar effects.…”

“…It is of note that these findings in two independent studies show similar effects. The variant CYP2C19 *3 (rs57081121) which lead to a decreased activity of the CYP2C19 has been associated with increased risk in Asians (Gan et al, 2011) and the variant CYP2C19 *17 (rs12248560) causing an ultra rapid metabolizer phenotype leads to a decreased HRT-related breast cancer risk in Europeans (Justenhoven et al, 2012). It is known that CYP2C19 catabolizes estrogens and progesterone (Yamazaki and Shimada, 1997; Cheng et al, 2001; Cribb et al, 2006) and the reported results suggest that increased metabolic activity of the CYP2C19 lowers endogenous hormone levels leading to a decreased risk.…”