CYP1A1 polymorphism and risk of gynecological malignancy in Japan

Abstract

The incidence of endometrial cancer and ovarian cancer in Japan has been increasing in recent years. Results of epidemiologic studies suggest that the onset and multiplication of these cancers are associated with estrogen. Estrogens are metabolized by cytochrome P450 1A1 (CYP1A1) and converted into catecholestrogens, which are carcinogens. CYP1A1 has several polymorphisms, the major one being T6235C transition in the non-coding 3′-flanking region (MspI polymorphism), and another being A4889G transition in exon 7 (Ile/Val polymorphism). These polymorphisms can affect the metabolites of estrogens and contribute to the susceptibility to gynecological malignancy. In this study, to determine whether CYP1A1 polymorphism plays a role in the development of gynecological malignancy in the Japanese population, we assessed the association of CYP1A1 polymorphism in Japanese patients with gynecological malignancy in comparison to that in controls. The odds ratios (ORs) of Ile/Val polymorphism were 1.16 in ovarian cancer patients and 1.70 in endometrial cancer patients. The ORs of MspI polymorphism were 1.33 in ovarian cancer patients and 0.88 in endometrial cancer patients. No significant association was found between these CYP1A1 polymorphisms and gynecological malignancy. Although the frequency of CYP1A1 polymorphism in the Japanese population is higher than that in the Caucasian population, CYP1A1 polymorphism is not related to gynecological malignancies in Japanese population.

Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the incidence of cervical cancer in Chhattisgarh

“…Moreover, the CYP1A1 Ile462Val polymorphism has shown to be a risk factor of cervical cancer in the Chinese population (Huang et al, 2006;Geng et al, 2010;Shi et al, 2011). On contrary to present findings, studies conducted in Polish and Japanese population did not find CYP1A1 Ile462Val polymorphism as an increased risk for cervical cancer (Sugawara et al, 2003;Roszak et al, 2014). Thus, it is obvious that cancer development may arise due to genetic polymorphism in metabolic enzyme.…”

Genetic Polymorphisms of Drug Metabolising Enzymes and Drug Transporters in Relation to Cancer Risk

“…However, no significant relation between CYP1A1 polymorphisms and gynaecological malignancies could be detected in other studies [45,46].…”

Cytochrome P450 1A1, cigarette smoking, and risk of endometrial cancer (United States)

“…The findings of previous studies investigating the association between CYP1A1 polymorphisms and endometrial cancer risk have been inconsistent [14][15][16][17][18][19][20] (Table 5). Esteller et al [14,15] conducted a small case-control study (n = 80 cases and 60 controls) and observed a statistically significant 3-to 4-fold increase in risk associated with carriage of the MspI allele and the Val462 allele [14], along with a 6-fold increase in risk associated with carriage of the Asn461 allele [15].…”

“…Contrary to the findings of Esteller et al [14,15], Doherty observed a statistically significant decrease in risk associated with the carriage of at least one MspI or Val462 allele and no decrease in risk was observed associated with the Asn461 allele. A Japanese case-control study and a Polish case-control study concluded no significant associations with the MspI, Ile462Val, and Thr461Asn polymorphisms and endometrial cancer risk [18,20]. Recently, a large population-based case-control study of 502 cases and 1,326 age-and race-matched controls concluded that there was a significant association with genotypes that contained any Val462 allele as compared with genotypes without a Val462 allele [17].…”

“…The CYP1A1 polymorphisms have been inconsistently associated with endometrial cancer risk [14][15][16][17][18][19][20]. Individual susceptibility to endometrial cancer may be partly explained by the variability in metabolic activities determined by the CYP1A1 polymorphisms for estrogen metabolism and activation of PAHs.…”