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

Abstract

Cytochrome P450 1A1 (CYP1A1) is involved in the metabolism of estradiol and the activation of polycyclic aromatic hydrocarbons found in tobacco products. Polymorphic variation in CYP1A1 activity may modify susceptibility to endometrial cancer through the oxidative metabolism of estradiol and the activation of tobacco-smoke constituents. We prospectively evaluated the associations between three common CYP1A1 polymorphisms and endometrial cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case-control study nested within the Nurses' Health Study. We investigated the MspI restriction-site polymorphism, a C --> A transversion at nucleotide 4887 (Thr461Asn) and a A --> G transition at nucleotide 4889 (Ile462Val) among 456 women with endometrial cancer and 1,134 matched controls. We used conditional logistic regression to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of endometrial cancer among subjects who had at least one variant allele compared with that of subjects homozygous for the wild-type allele. We did not observe any statistically significant associations between the MspI, Thr461Asn or Ile462Val polymorphisms and endometrial cancer risk or any significant effect modification by cigarette-smoking status. These data suggest that these three polymorphisms are not important in determining genetic susceptibility to endometrial cancer, although larger sample sizes are needed to confirm these findings.

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

“…Regardless of dominant model, recessive model or co-dominant models, the result is invariably negative. The meta-analysis results are consistent with some studies (Sugawara et al, 2003;McGrath et al, 2007;Ashton et al, 2010).…”

“…Of these, a total of 9 studies met the inclusion criteria Sugawara et al, 2003;Doherty et al, 2005;Seremak-Mrozikiewicz et al, 2005;Esinler et al, 2006;McGrath et al, 2007;Hirata et al, 2008;Ashton et al, 2010). Among them, however, one study was excluded because the same data was repeated in other study .…”

“…Unfortunately, the conclusions on the association between CYP1A1 Ile462Val polymorphism and endometrial cancer risk from different studies are inconsistent. Some studies reported that no significant association was found between CYP1A1 Ile462Val polymorphism and endometrial cancer risk (Sugawara et al, 2001;McGrath et al, 2007;Ashton et al, 2010). However, other studies concluded that there was a significant association between CYP1A1 Ile462Val polymorphism and endometrial cancer risk Sugawara et al, 2003;Doherty et al, 2005;Seremak-Mrozikiewicz et al, 2005;Esinler et al, 2006;Rebbeck et al, 2006;Hirata et al, 2008;Ashton et al, 2010).…”

Cytochrome P450 1A1 Gene Polymorphisms and Endometrial Cancer Risk: A Meta-Analysis

“…Regarding race, 7 studies were performed on Caucasian subjects 14,15,17,19Y21,24 (1349 cases and 2305 controls), 1 study was performed on Asian subjects, 22 and 1 study was performed on mixed populations. 18 Regarding Thr461Asn polymorphism, 6 studies were eligible 14,15,17,20,21,23 (1272 cases and 2122 controls), which were all performed on Caucasian subjects.…”

Genetic polymorphisms and endometrial cancer risk

“…McGrath et al . performed a large case-control study nested within the Nurses’ Health Study in which the same MspI restriction site polymorphism T→C transition as above was evaluated, along with a C→A change at nucleotide 4887(Thr461Asn) and a A→G change at nucleotide 4889 (Ile462Val), were analyzed [45]. This study included 456 women with endometrial cancer and 1134 controls matched by year of birth, menopausal status and postmenopausal hormone use at the time of the blood draw.…”