Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

Abstract

SummaryThe incidence of breast cancer has been greatly increasing in Taiwan over the past two decades. Since cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens or oestrogen, we hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for breast cancer. This hypothesis was evaluated in this case control study of 150 breast cancer patients and 150 healthy controls among Chinese women. Two CYP1A1 polymorphisms were studied, one containing a new Msp1 site and the other located in axon 7 and resulting in the replacement of an isoleucine (Ile) residue by a valine (Val). After simultaneously considering the known or significant risk factors for breast cancer, including the age of study participants, positive family history of breast cancer, early menarche (≤ 13 years), nulliparity and late first full-term pregnancy (≥ 30 years), hormone replacement therapy and smoking, the CYP1A1 Msp1 polymorphism was found to be a significant factor in determining the risk of breast cancer. The homozygous variant was the most susceptible genotype with an adjusted odds ratio of 1.98 (95% confidence interval (CI) = 1.01-3.99) compared with the non-homozygous variants (the homozygous wild-type and the heterozygous variant). In contrast, the CYP1A1 Ile/Val polymorphism was not significantly associated with breast cancer development (adjusted OR = 1.07, 95% CI = 0.64-1.78). Interestingly, the Msp1 polymorphism was especially significant in postmenopausal women, but not in premenopausal women. Further stratification analysis in postmenopausal women who were non-smokers and with no history of hormone replacement therapy showed the cancer risk due to the Msp1 variant to be more significant in women with early menarche. We conclude that CYP1A1 polymorphism is a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Further study with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

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

“…Out of the 91 abstracts retrieved through the search criteria, 39 were irrelevant, eight articles [20][21][22][23][24][25][26][27] were excluded because they were conducted on overlapping populations with other eligible studies [28][29][30][31][32][33][34][35] (these excluded articles represent smaller studies performed on subsets of larger eligible studies), three articles were reviews/meta-analyses [4,11,36], and four studies were excluded due to reporting reasons [37][38][39][40], i.e., no reporting of the relevant genotype frequencies.…”

Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis

“…However, in the east-Asians subgroup analysis of A2455G, if any single study was excluded from the subgroup, the results were not significant, either in recessive (G/G vs G/A + A/A) or in additive (G/G vs A/A) models. Furthermore, in the premenopausal subgroup analysis of A2455G, when the study of Huang et al (1999b) was excluded, the pooled result was not significant, while exclusion of other studies did not influence the result. Thus, the association between A2455G and breast cancer risk in the pre-menopausal and eastAsians results must be treated with caution.…”

“…Based on the search criteria, 17 articles (Ambrosone et al 1995;Bailey et al 1998;Basham et al 2001;Boyapati et al 2005;Chacko et al 2005;Hefler et al 2004;Huang et al 1999aHuang et al , 1999bKrajinovic et al 2001;Le Marchand et al 2005;Li et al 2004;Miyoshi et al 2002;Okobia et al 2005;Shen et al 2006;Singh et al 2006;Taioli et al 1995Taioli et al , 1999 were identified by reviewing 66 papers. Two of these articles were finally excluded as the studies of Taioli et al (1995) and Huang et al (1999a) were replaced by their later reports (Taioli et al 1999;Huang et al 1999b, respectively).…”

The CYP19 TTTA Repeat Polymorphism Is Related to the Prognosis of Premenopausal Stage I–II and Operable Stage III Breast Cancers

“…Most had been invited to take part in our previous molecular epidemiological studies [17][18][19][20], aimed at defining the contribution of genotypic polymorphisms of carcinogen-and estrogen-metabolizing genes as susceptibility factors for breast cancer development in Taiwan. Genomic DNA and detailed demographic information were obtained from the patients with their consent.…”