CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.
OBJECTIVE
Gene-environment interactions have been the focus of a number of recent studies of the occurrence of human cancers, and an association between the risk and the CYP1A1*3 polymorphism has been noticed for several cancers. Previous studies suggest that estrogens are involved in the etiology of ovarian cancer. The cytochrome P450 1A1 (CYP1A1) gene polymorphism may play role in the development of epithelial ovarian neoplasm by detoxification of polycyclic hydrocarbons and other compounds and the concentration of estrogens and their metabolites. Therefore, we assessed the association of CYP1A1 gene polymorphism in patients with epithelial ovarian neoplasm in the Turkish populations through a case-control study.


METHODS
Using an allele-specific polymerase chain reaction (PCR)-based method, CYP1A1*3 polymorphism, in exon 7 of the gene, was analyzed in 117 epithelial ovarian neoplasm patients and 202 control subjects.


RESULTS
The CYP1A1 Ile/Val genotype significantly increased the risk for patients with epithelial ovarian neoplasm (OR 5.7, 95% CI 3.34-9.76). Furthermore, there were statistical differences in the distribution of CYP1A1 Val/Val genotype among all patients (OR 5.85, 95% CI 2.40-14.25). In other words, the presence of the Val allele significantly increased the risk of epithelial ovarian neoplasm. Among benign tumors, the frequency of Ile/Val and Val/Val genotypes was found to be statistically significant with an ORs of 6.01 and 4.38 (95% CI 2.61-13.84 and 1.04-18.38, respectively). In the benign serous ovarian tumors, patients with Ile/Val and Val/Val revealed a 7.2- and 10.5-fold higher risk of having ovarian carcinoma (95% CI 2.22-23.40 and 2.16-51.19), respectively. In the benign mucinous ovarian carcinoma patients, the frequency of Ile/Val was found to be statistically significant with an OR of 5.15 (95% CI 1.75-15.16). However, no patient with Val/Val genotype was observed in this group and no statistical distribution was performed. Among borderline tumors, CYP1A1 Ile/Val genotype significantly increased the risk for patients (OR 5.15, 95% CI 1.75-15.16). However, only one patient was observed with the Val/Val allele and the frequency of this genotype was not found to be statistically different with an OR of 2.50 (95% CI 0.27-22.64). Among ovarian cancer patients, there were statistically differences in the distribution of CYP1A1 Ile/Val and Val/Val genotypes (OR 5.73, 95% CI 3.04-10.76; and OR 7.42, 95% CI 2.80-19.66), suggesting that patients carrying these genotypes were at increased risk for ovarian carcinoma. In serous carcinoma, patients with CYP1A1 Ile/Val and Val/Val revealed a 6.5- and 10-fold higher risk of having ovarian cancer (OR 7.09, 95% CI 3.30-15.22; and OR 8.77, 95% CI 2.83-27.14). In mucinous carcinoma, patients with CYP1A1 Ile/Val and Val/Val also revealed a 5.4 and 10.5 times higher risk of having ovarian cancer. There were no statistical significance in the distribution of Val allele among endometroid-type cancer patients.


CONCLUSIONS
Our data, although based on a small number of subjects, suggest that variant alleles of CYP1A1 gene in ovarian epithelial cells, directly or through other components, may contribute to initiation of ovarian carcinogenesis.
Aktas
Dilek
D
Department of Genetics, Hacettepe University Medical School, 06100, Sihhiye, Ankara, Turkey. dilekaktas6@hotmail.com
Guney
Inci
I
Alikasifoglu
Mehmet
M
Yüce
Kunter
K
Tuncbilek
Ergul
E
Ayhan
Ali
A
D002288:Adenocarcinoma, Mucinous / Q000235:genetics; D000328:Adult; D000483:Alleles; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003536:Cystadenocarcinoma / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D007532:Isoleucine / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012306:Risk; D014421:Turkey / Q000453:epidemiology; D014633:Valine / Q000378:metabolism
D007532:Isoleucine; D019363:Cytochrome P-450 CYP1A1; D014633:Valine