Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women.
Estrogen and its metabolites are believed to play important roles in breast cancer, and its determinants include both genetic and lifestyle factors. The objective of the study is to investigate the association of breast cancer risk in Thailand with genetic polymorphisms in several genes involved in estrogen synthesis and metabolism. Five hundred and seventy patients with histopathologically confirmed breast cancer and 497 controls were included in the present study. Forty single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2, CYP1B1, CYP17, CYP19, CYP2C9, CYP2C19, AhR, ESR1, PGR, ERRG, COMT, HSD17B1, HSD17B2, EPHX1 and NQO1 genes were genotyped. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression, which suggested an altered risk for the following SNPs [gene, odds ratio (OR) and 95% confidence interval are shown]: heterozygote carriers of rs4917623 [CYP2C19, OR = 1.38 (1.04-1.84)], rs2066853 [AhR, OR = 1.34 (1.02-1.76)] and rs1857407 [ERRG, (OR = 0.72 (0.55-0.96)]; homozygote carriers of rs762551 [CYP1A2, OR = 2.75 (1.47-5.14)], rs4917623 [CYP2C19, OR = 1.48 (1.00-2.19) and rs945453 [ERRG, OR = 1.66 (1.04-2.65)]. In addition, a stratified analysis by menopausal status indicated that the association of the CYP1A2 (rs762551) and CYP17 (rs743572) polymorphisms with breast cancer risk were mainly evident in premenopausal, while ERRG (rs1857407) was significant in postmenopausal women. These findings suggest that CYP1A2, CYP2C19, AhR, ERRG and CYP17 polymorphisms may play an important role in estrogen metabolism and modify individual susceptibility to breast cancer in Thai women.
Research Division, National Cancer Institute, Ratchathewi, Bangkok, Thailand.
Suleeporn
S
Sangrajrang
Yasunori
Y
Sato
Hiromi
H
Sakamoto
Sumiko
S
Ohnami
Nan M
NM
Laird
Thiravud
T
Khuhaprema
Paul
P
Brennan
Paolo
P
Boffetta
Teruhiko
T
Yoshida
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004798:Enzymes / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013785:Thailand / Q000453:epidemiology
D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D004798:Enzymes; D004967:Estrogens; D009363:Neoplasm Proteins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D013254:Steroid 17-alpha-Hydroxylase; C111235:AHR protein, human; C490917:ESRRG protein, human; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human