Mol. Hum. Reprod. Advance Access originally published online on April 20, 2007
Molecular Human Reproduction 2007 13(6):399-404; doi:10.1093/molehr/gam018
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Interaction between cytochrome P450 gene polymorphisms and serum organochlorine TEQ levels in the risk of endometriosis
1 Epidemiology and Prevention Division, Research Center for Cancer prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan 2 Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan 3 Department of Public Health, University of Miyazaki, Miyazaki, Japan 4 Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
5 Correspondence address. Tel: +81-3-3542-2511 (ext 3391); Fax: +81-3-3547-8578; E-mail: moiwasak{at}gan2.res.ncc.go.jp
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.
Key words: CYP1A1/CYP1B1/endometriosis/gene–environment interaction/organochlorine
Submitted on January 22, 2007; resubmitted on February 28, 2007; accepted on March 1, 2007.