Estrogen‐metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women

Abstract

BACKGROUNDGenes encoding enzymes involved in estrogen metabolism are held to be candidate genes for associations with breast disease. In these candidate genes, no critical combination of single‐nucleotide polymorphisms (SNPs) for assessing breast carcinoma risk has been reported to date.METHODSIn a large case–control study, the authors investigated 10 estrogen‐metabolizing SNPs in 396 patients with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control patients without breast carcinoma in their personal history. The following 10 SNPs were analyzed using sequencing‐on‐chip technology via a solid‐phase polymerase chain reaction assay performed on oligonucleotide microarrays: catechol‐O‐methyltransferase Val158Met G→A, 17‐beta‐hydroxysteroid dehydrogenase type 1 vIV A→C, cytochrome P‐450 (CYP) family 17 A2 allele T→C, CYP1A1‐1 MspI restriction fragment length polymorphism (RFLP) T→C, CYP1A1‐2 Ile462Val A→G, CYP19‐1 Trp39Arg T→C, CYP19‐2 Arg264Cys C→T, CYP19‐3 Cys1558Thr C→T, steroid‐5‐alpha reductase type 2 Val89Leu G→C, and vitamin D receptor BsmI RFLP. A total of 21,350 genotypes were evaluated. Associations and two‐way interaction models were calculated using stepwise logistic regression.RESULTSIn a multiple model, CYP1A1‐1 (P = 0.004) and CYP1A1‐2 (P = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. When two‐way interactions involving investigated SNPs were ascertained, no significant interactions among polymorphisms were noted. Comparison of patients with fibroadenoma with control patients revealed significantly increased and decreased risks of fibroadenoma when the mutant alleles of CYP17 (P = 0.02) and CYP1A1‐1 (P = 0.04), respectively, were present.CONCLUSIONSThe authors obtained the first SNP data indicating that CYP17 and CYP1A1‐1 play a role in the pathogenesis of fibroadenoma. Although the authors were not able to develop interaction models involving SNPs, they did provide evidence that CYP1A1 is a low‐penetrance susceptibility gene with respect to breast carcinoma in a large series of Caucasian women. Cancer 2004. © 2004 American Cancer Society.

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

“…Among all the eligible articles, four described the T3801C polymorphism, two focused on A2455G, and nine articles investigated both T3801C and A2455G. In these latter nine articles, the genotyping data for T3801C deviated from HWE in Chacko et al (2005), Taioli et al (1999) and Bailey et al (1998), while the genotyping data for A2455G matched HWE in these three studies; the genotyping data for A2455G in Hefler et al (2004) deviated from HWE, while the genotyping data for T3801C matched HWE in this paper. We extracted the available data, rejected datasets where HWE was doubtful.…”

“…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).…”

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

“…Similarly, when the analysis was stratified by race, no significant associations were detected (data not shown). Examining genotype frequencies in controls, significant deviation from HWE was detected in two studies [48,69], which were both performed on Caucasian subjects. After the exclusion of the two studies significantly departing from HWE the associations demonstrated in Caucasian populations retained their statistical significance.…”

Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women

“…Several studies have been conducted on the association between polymorphisms of the CYP1A1 gene and breast cancer risk (Ambrosone et al, 1995;Taioli et al, 1995;Bailey et al, 1998;Ishibe et al, 1998;Huang et al, 1999;Basham et al, 2001;Krajinovic et al, 2001;da Fonte de Amorim et al, 2002;Laden et al, 2002;Miyoshi and Noguchi, 2003;Hefler et al, 2004;Li et al, 2004;Boyapati et al, 2005;Masson et al, 2005). Overall, the Ile462Val polymorphism was found to show a null or weak association with breast cancer risk (Masson et al, 2005), whereas 1.36-5.22 fold increases in breast cancer risk were reported in subgroups of smokers or in women with higher serum polychlorinated-biphenyls (PCB) levels (Miyoshi and Noguchi, 2003).…”

“…The CYP1A1 Ile462Val polymorphism in exon 7 and the T6235C polymorphism on the 3' non-coding region (MspI) have been intensively studied in relation to breast cancer risk (Ambrosone et al, 1995;Taioli et al, 1995;Bailey et al, 1998;Ishibe et al, 1998;Huang et al, 1999;Basham et al, 2001;Krajinovic et al, 2001;da Fonte de Amorim et al, 2002;Laden et al, 2002;Miyoshi and Noguchi, 2003;Hefler et al, 2004;Li et al, 2004;Boyapati et al, 2005;Masson et al, 2005). The Val allele of the Ile462Val polymorphism was found to be related with increased CYP1A1 gene inducibility (Cosma et al, 1993b;Crofts et al, 1994), and the MspI polymorphic site was observed to have an effect on gene inducibility in subjects with variant alleles when combined with the Ile462Val polymorphism (Crofts et al, 1994).…”