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

Ashton, Katie A.; Proietto, Anthony; Otton, Geoffrey; Symonds, Ian; McEvoy, Mark; Attia, John; Gilbert, Michael; Hamann, Ute; Scott, Rodney J.

doi:10.1016/j.canep.2010.03.005

Cited by 62 publications

(60 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Its pathogenesis still remains poorly understood although the prevailing hypothesis is that a dominant oestrogenic environment favours EC development [1,2], and some gene variants for enzymes in sex-steroid synthesis pathways could also contribute to the hyperoestrogenic status associated with the risk of EC [3,4]. Oral contraceptives confer long-term protection against EC [5], while long-term sequential oestrogen plus progestogen use in menopause is known to increase the EC risk, and continuous combined oestrogen þ progestogen therapy in menopause is known to reduce EC risk [6].…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Hernandez

Pasupuleti

Benítes-Zapata

et al. 2015

European Journal of Cancer

133

View full text Add to dashboard Cite

Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by NewcastleeOttawa scale. Randomeffects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n Z 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04e52.85, p Z 0.0004). No differences were seen in postmenopausal versus pre-and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n Z 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% * Corresponding author: Research Center, School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Building F, Campus Villa, Avenida Alameda de San Marcos Cuadra 2 s/n, Chorrillos, Lima 9, Peru. Tel.: þ51 1 3133333x2730.E-mail addresses: adrianhernandezdiaz@gmail.com (A.V. Hernandez), lepiscean@gmail.com (V. Pasupuleti), vbeniteszapata@gmail. com (V.A. Benites-Zapata), tpriyaleela@gmail.com (P. Thota), abhishekdp@gmail.com (A. Deshpande), faustino.perez@unizar.es (F.R. Perez-Lopez).1 Contributed equally to the study.

show abstract

Section: Introductionmentioning

confidence: 99%

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Hernandez

Pasupuleti

Benítes-Zapata

et al. 2015

European Journal of Cancer

133

View full text Add to dashboard Cite

show abstract

“…A polymorphic CAG repeat in exon 1 of the AR gene is well known to encode a polyglutamine tract and to increase the length of CAG repeat, which is also well known to be associated with decreased transactivation activities (Chamberlain et al 1994). Of particular interest, a statistically significant inverse association has been reported between increased CAG repeat length and endometrial carcinoma risk in case-control studies (McGrath et al 2006, Ashton et al 2010, although controversies exist (Yang et al 2009). On the other hand, Yang and coworkers evaluated 36 sex hormone-related genes using a tagging approach in a population-based case-control study of 417 endometrial carcinoma cases and reported that the possible evidence of the correlation with endometrial cancer risk could be the common genetic variation in 23:7 AR (Yang et al 2010).…”

Section: Structure Of Androgen Receptormentioning

confidence: 99%

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Itō¹,

Miki²,

Suzuki³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.

show abstract

“…Five different enzymes have been identified in this system, which are involved in estrogen synthesis and degradation. Cytochrome P450 17a (CYP17) and cytochrome P450 19 (CYP19 or aromatase) control the early and terminal steps of the estrogen biosynthesis pathway respectively (12).…”

Section: Introductionmentioning

confidence: 99%

“…Catechol-O-methyl transferase catalyzes the excretion of carcinogenic 4-hydroxy estrogen metabolites (12). Certain evidence has shown that human endometrial epithelium produce cytochrome P450 (CYP P450) metabolic enzymes that generate genotoxic intermediates and affect ESRs.…”

Section: Introductionmentioning

confidence: 99%

Association of polymorphisms and haplotypes in the cytochrome P450 1B1 gene with uterine leiomyoma: A case control study

et al. 2014

View full text Add to dashboard Cite

Abstract. Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus and estrogen metabolizing enzymes affect its promotion and progression. The aim of the present study was to evaluate the association between four single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) gene and UL risk. Four SNPs of the CYP1B1 gene in 105 UL patients and 112 unrelated healthy controls were genotyped using a direct sequencing method. Haplotype analyses were performed with UNPHASED software and linkage disequilibrium (LD) was assessed by Haploview software. There were no associations between Leu432Val (rs1056836), Asp449Asp (rs1056837) and Asn453Ser (rs1800440) polymorphisms of the CYP1B1 gene and UL. Although the genotypic frequencies of the Arg368His (rs79204362) polymorphism did not differ between the two groups, the frequency of A (His) allele was significantly higher in UL females (P= 0.02). In addition, the frequency of GTAA haplotype was significantly higher in the controls and played a protective role in UL susceptibility. A strong LD between the three common SNPs (rs1056836, rs1056837 and rs1800440) in the CYP1B1 gene was observed in the population. In conclusion, a higher frequency of the CYP1B1 368His (A) allele was observed in UL females. The frequency of the GTAA haplotype was significantly higher in healthy females and this haplotype played a protective role in UL susceptibility.

show abstract

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

Cited by 62 publications

References 40 publications

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Association of polymorphisms and haplotypes in the cytochrome P450 1B1 gene with uterine leiomyoma: A case control study

Contact Info

Product

Resources

About