Polymorphisms in the CYP19A1 (Aromatase) Gene and Endometrial Cancer Risk in Chinese Women

Abstract

Aromatase, encoded by the CYP19A1 gene, is a key enzyme in estradiol biosynthesis, which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Given the critical role of estrogen in the development of endometrial cancer risk, we evaluated genetic polymorphisms of the CYP19A1 gene, including rs1065779, rs700519, rs28566535, rs752760, and rs1870050, in association with endometrial cancer in a population-based case-control study conducted in Shanghai, China. Genotypes of 1,040 incident endometrial cancer cases and 1,031 frequencymatched controls were included in the study. We applied a logistic regression model to derive adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Six common haplotypes with a frequency z5% were estimated; the highest frequency haplotype was GCACA (27.8% in cases and 26.2% in controls). We observed an inverse association between CYP19A1 haplotype TCATC and endometrial cancer in our population (OR, 0.76; 95% CI,). An inverse association was found between endometrial cancer and single nucleotide polymorphism rs1870050 in the promoter region with ORs of 0.81 (95% CI, 0.68-0.97) and 0.58 (95% CI, 0.42-0.80) for the AC and CC genotypes, respectively. We observed a multiplicative interaction between single nucleotide polymorphism rs700519 and body mass index among postmenopausal women (P = 0.01), with stronger associations between rs700519 genotypes and endometrial cancer risk among heavier (body mass index, z25) postmenopausal women. In summary, our data show that polymorphisms in the CYP19A1 gene may contribute to endometrial carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(5):943 -9)

Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk

“…However, the majority of these studies suggest that there is no overall relationship with endometrial cancer [12,[27][28][29][30][31][32]. Specifically for the rs1800440 polymorphism of CYP1B1, two studies found no association with endometrial cancer risk [30,31], however, one study by McGrath et al (2004) revealed that women with the variant genotypes (AG + GG) had a decreased risk of endometrial cancer compared to women with the wild-type (AA) genotype [28].…”

Adiposity and cancer risk: new mechanistic insights from epidemiology

“…More than 50 gene loci have been associated with the development of obesity through genomewide association studies but few Mendelian randomization studies have been undertaken to date 157,158 . These focused on few gene loci and cancers, including polymorphisms in the CYP19A1 gene (which encodes aromatase) 159 , Figure 3 | Hypothesized steatosis-hepatocellular carcinoma pathway. In the absence of common hepatic insults, such as excess alcohol, accumulation of fat in the liver (nonalcoholic fatty liver disease (NAFLD)) is associated with chronic inflammation, known as nonalcoholic steatohepatitis (NASH).…”

Identification of CYP19A1 single-nucleotide polymorphisms and their haplotype distributions in a Korean population

“…4 The 1531C4T (rs10046) allele has been studied extensively, which includes its potential gender-specific association with essential hypertension, 8 increased level of estrogen, 19 breast cancer risk in Japanese populations 20 and endometrial cancer risk in Chinese women. 21 This variant, observed at 56% frequency in this study and located in haplotype block 3, exhibited a haplotype structure with IVS7-79A4G, IVS6-106 T4G, IVS6+36A4T and IVS5-16T4G (D¢¼1, r 2 ¼0.92-0.96) in block 3 (Figures 2a and b). A set of tag SNPs, which will be useful for association mapping studies, were determined (Figure 2b).…”