Interaction between cytochrome P450 gene polymorphisms and serum organochlorine TEQ levels in the risk of endometriosis.
Exposure to dioxins and polychlorinated biphenyls (PCBs) has been suggested as a possible etiologic factor for endometriosis, but the association remains highly controversial. To assess whether cytochrome P450 (CYP) gene polymorphisms modulate the effect of dioxins and/or PCBs in endometriosis risk, we conducted a case-control study among infertile Japanese women. A total of 138 eligible women aged 20-45 were diagnosed laparoscopically and classified into three subgroups: control (no endometriosis), early endometriosis (stages I-II) and advanced endometriosis (stages III-IV). Neither CYP1A1 Ile462Val and CYP1B1 Leu432Val polymorphisms (genotypes with versus genotypes without the minor allele) nor serum dioxin and PCB toxic equivalency (TEQ) levels (low versus high) were independently associated with either early or advanced endometriosis risk. However, genotypes with the CYP1A1 462Val allele showed a statistically significant reduced risk of advanced endometriosis in combination with high serum dioxin TEQ levels (adjusted odds ratio = 0.13, 95% confidence interval: 0.02-0.76) (P for interaction = 0.08). Although no association was found between serum PCB TEQ level and advanced endometriosis in any stratum of CYP1B1 Leu432Val polymorphism, a statistically significant interaction was found (P for interaction = 0.05). CYP1A1 and CYP1B1 polymorphisms may modify the relation between environmental exposure to organochlorine and advanced endometriosis risk.
Tsuchiya
Masaki
M
Epidemiology and Prevention Division, Research Center for Cancer prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Tokyo, 104-0045, Japan.
Tsukino
Hiromasa
H
Iwasaki
Motoki
M
Sasaki
Hiroshi
H
Tanaka
Tadao
T
Katoh
Takahiko
T
Patterson
Donald G
DG
Turner
Wayman
W
Needham
Larry
L
Tsugane
Shoichiro
S
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004147:Dioxins / Q000097:blood / Q000633:toxicity*; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D004147:Dioxins; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1