Genetic variants of CYP19 (aromatase) and breast cancer risk

Kristensen, Vessela N.; Harada, Nobuhiro; Yoshimura, Nagahisa; Haraldsen, E; Lønning, Per Eystein; Erikstein, Bjørn; Kåresen, Rolf; Kristensen, Tom; Børresen-Dale, Anne Lise

doi:10.1038/sj.onc.1203425

Cited by 155 publications

(134 citation statements)

References 17 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…It is unclear whether Hap3 functionally affects CIN risk. However, MTHFR A1298C is a functional variant and 5 0 flank polymorphism may have functional significance by affecting mRNA stability or regulation of translation [33,34].…”

Section: Discussionmentioning

confidence: 99%

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

Tong

Lee

Song

et al. 2009

Cancer Causes Control

View full text Add to dashboard Cite

The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 casecontrol samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

Tong

Lee

Song

et al. 2009

Cancer Causes Control

View full text Add to dashboard Cite

show abstract

“…Block 4 SNPs were located in the coding region and 3 0 UTR, which may have functional significance by affecting mRNA stability or regulation of translation termination. 23 These SNPs may also be in strong LD with other functional variants elsewhere in the block. Block 3 SNPs were between the promoter I.f and I.2, which were expressed in brain and placenta, respectively.…”

Section: Discussionmentioning

confidence: 99%

CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes in Chinese women

et al. 2006

View full text Add to dashboard Cite

The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus affects body fat distribution and regulation. Object: To examine the relationship between genetic polymorphisms of the CYP19A1 gene and obesity-related phenotypes, body mass index (BMI) and waist-to-hip ratio (WHR). Subjects: In total, 1241 Chinese women, who were recruited as community controls for a population-based case-control study of breast cancer. Methods: Nineteen haplotype tagging single nucleotide polymorphisms (htSNPs) in four haplotype blocks were genotyped. Results: Significant associations were observed for WHR at three SNPs that are located in haplotype block 1, including rs2445765, rs1004984 and rs1902584 (P ¼ 0.05, 0.04 and 0.01, respectively). Women, particularly premenopausal women, who carried the minor allele at any of these SNPs, had higher WHR than those without it. Of these three SNPs, the strongest association was observed at rs1902584, which is the closest to Promoter I.4, the major promoter for adipose tissue. Haplotype analyses indicated an association between the haplotype TCCAT in block 1 and WHR with a P-value of 0.02. Conclusion: These results suggested that CYP19A1 genetic polymorphisms may be associated with the risk of obesity among Chinese women, especially among premenopausal women.

show abstract

“…The variant T allele was previously suggested to be associated with a high estrogen profile because it was correlated with tumor aromatase mRNA levels. The variant T allele is associated with alternative promoter use (Somner et al 2004), and Kristensen et al (2000) found that it was more frequent in breast cancer cases than in their controls. Other studies have found no association between the 1531C>T polymorphism and breast cancer risk, and the present study found that the CYP19 1531C>T polymorphism is not associated with the risk of endometriosis.…”

Section: Discussionmentioning

confidence: 99%

“…The CYP19 gene has several polymorphisms: a [TTTA]n tetranucleotide repeat polymorphism in intron 4 (Healey et al 2000;Kristensen et al 2000), a 115T>C polymorphism in exon 2 (Trp39Arg) (Miyoshi et al 2000), a silent 240A>G polymorphism at codon 80 in exon 3 (Siegelmann-Danieli and Buetow 1999), a 790C>T polymorphism in exon 8 (Arg264Cys) (Toda et al 1990;Kristensen et al 2000;Lee et al 2003), and a 1531C>T polymorphism in the 3¢ untranslated region of exon 10 (Sourdaine et al 1994). CYP19 gene polymorphisms are reportedly associated with estrogen-dependent diseases, such as uterine myoma, endometriosis, breast cancer, and endometrial cancer (Hirose et al 2004;Bulun et al 2005;Paynter et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis

Hur

Lee

et al. 2007

J Hum Genet

View full text Add to dashboard Cite

A variety of factors affect the development of endometriosis, including hormonal status and genetic factors. The growth of endometriosis is stimulated by local estrogen production in conjunction with circulating estrogen. The CYP19 gene encodes a steroid aromatase that catalyses the conversion of C-19 androgens to estrogens. This study investigated whether polymorphisms of the CYP19 gene are associated with the risk of advanced endometriosis in Korean women. Blood samples were collected from 224 female patients with endometriosis of stages III and IV, as diagnosed by both pathologic and laparoscopic findings, and from a control group comprising of 188 women undergoing laparoscopic surgery or laparotomy for nonmalignant lesions. Single-nucleotide polymorphisms, restriction fragment length polymorphisms, and tetranucleotide tandem repeat polymorphisms were discriminated by the polymerase chain reaction (PCR). Haplotype analysis was also performed. CYP19 115T>C, 240G>A, and 1531C>T polymorphisms and [TTTA]n tetranucleotide repeat polymorphisms in the CYP19 gene and their haplotypes were not significantly associated with the risk of endometriosis. The risk of endometriosis also did not increase significantly with the number of higher risk alleles of the CYP19 gene. In conclusion, our findings suggest that CYP19 genetic polymorphisms are not associated with advanced-stage endometriosis in Korean women.

show abstract

Genetic variants of CYP19 (aromatase) and breast cancer risk

Cited by 155 publications

References 17 publications

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes in Chinese women

Polymorphisms and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis

Contact Info

Product

Resources

About