Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer

Doherty, Jennifer A.; Weiss, Noel S.; Freeman, Robert J.; Dightman, Douglas A.; Thornton, Perry J.; Houck, J. R.; Voigt, Lynda F.; Rossing, Mary Anne; Schwartz, Stephen M.; Chen, Chu

doi:10.1158/1055-9965.epi-04-0479

Cited by 69 publications

(88 citation statements)

References 64 publications

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“…In contrast to the limited population studies on codons 62 and 72, the polymorphism at the 158 codon has been extensively studied in a variety of cancers, although none involve RCC. Nonetheless, as was the case in this study, the codon 158 variant was also observed to be nonassociated with other types of cancers such as ovarian (48), bladder (37), endometrial (39), and liver cancers (38), and was inconclusive in breast cancer (reviewed in ref. 36).…”

Section: Discussionsupporting

confidence: 64%

“…Although the base change on this codon does not lead to an amino acid change, studies show that synonymous mutations could lead to structural changes in mRNA (31)(32)(33), and as a result, causes altered protein expression (32) as well as disease (33). Furthermore, polymorphisms of COMT have been found to have associations with neurologic/psychological diseases (34,35) and have also been investigated in various cancers such as breast (36), bladder (37), liver (38), endometrial (39), and prostate (40) cancers.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Tanaka

Hirata

Chen

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in malignant transformation of male kidneys. To counteract the effects of this catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of neutralizing the genotoxic effects of this compound. A polymorphic variant of COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male population was used and the genetic distributions of COMT polymorphisms at codons 62 (C!T), 72 (G!T), and 158 (G!A) were analyzed in 157 normal healthy subjects and 123 sporadic RCC (clear cell type) samples by using a sequence-specific PCR technique. These experiments show that the variant genotype (P = 0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73, respectively, for the T/T genotype as compared with wild-type. No associations for renal cancer were found at either codons 72 or 158 in this Japanese male population. However, codons 62 and 158 were observed to be in linkage disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating the risk of COMT polymorphisms with grade of cancer, no associations were observed for any of the genotypes. This study is the first to report COMT polymorphism to be associated with RCC. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of RCC.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Tanaka

Hirata

Chen

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…CYP1B1*3 alleles are associated with biased formation of 4-hydroxyestradiol, which is potentially carcinogenic, 18,43 compared to formation of the lower risk 2-hydroxyestradiol metabolite. 43 Consequently, the role of CYP1B1 in estrogen metabolism 17,19,20 may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele. This study was performed in a small sample size and the data should be considered preliminary until validated in a large, prospective study.…”

Section: Resultsmentioning

confidence: 99%

Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer

Marsh

Somlo

et al. 2007

Pharmacogenomics J

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Paclitaxel is commonly used in the treatment of breast cancer. Variability in paclitaxel clearance may contribute to the unpredictability of clinical outcomes. We assessed genomic DNA from the plasma of 93 patients with high-risk primary or stage IV breast cancer, who received dose-intense paclitaxel, doxorubicin and cyclophosphamide. Eight polymorphisms in six genes associated with metabolism and transport of paclitaxel were analyzed using Pyrosequencing. We found no association between ABCB1, ABCG2, CYP1B1, CYP3A4, CYP3A5 and CYP2C8 genotypes and paclitaxel clearance. However, patients homozygous for the CYP1B1*3 allele had a significantly longer progression-free survival than patients with at least one Valine allele (P ¼ 0.037). This finding could reflect altered paclitaxel metabolism, however, the finding was independent of paclitaxel clearance. Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele.

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“…Functionally relevant genetic variants exist in each of these genes. However, it remains unclear whether these genes affect breast cancer risk (3)(4)(5)(6)(7)(8)(9)(10), and there is even less information about whether these genes interact with relevant exposures to influence breast cancer etiology. Therefore, we evaluated whether there was evidence for modification of the effect of CHRT use by genes involved in the downstream metabolism of estrogens including COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1.…”

Section: Introductionmentioning

confidence: 99%

Lack of Effect Modification between Estrogen Metabolism Genotypes and Combined Hormone Replacement Therapy in Postmenopausal Breast Cancer Risk

Rebbeck¹,

Troxel²,

Shatalova

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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IntroductionPostmenopausal use of combined hormone replacement therapy (CHRT) containing both estrogens and progestins has been associated with increased breast cancer risk (1, 2). There is also evidence that genetic variants in candidate estrogen metabolism genes influence the disposition of exogenous estrogen. The genes involved in the disposition of estrogen are well known, and include catechol-O -methyltransferase (COMT), the sulfotransferases SULT1A1 and SULT1E1, and members of the cytochrome P50 family including CYP1B1, CYP1A2, and CYP1A1. Functionally relevant genetic variants exist in each of these genes. However, it remains unclear whether these genes affect breast cancer risk (3-10), and there is even less information about whether these genes interact with relevant exposures to influence breast cancer etiology. Therefore, we evaluated whether there was evidence for modification of the effect of CHRT use by genes involved in the downstream metabolism of estrogens including COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1. Materials and MethodsThe Women's Insights and Shared Experiences (WISE) study is a population-based case-control study that consisted of an efficient sampling design using shared controls to compare both breast cancer cases and endometrial cancer cases (11,12). Incident breast cancer cases were identified through hospitals and the Pennsylvania State Cancer Registry, and frequency-matched controls were identified from the community using random-digit dialing. The source populations for this study were the three counties of Philadelphia (PA), Delaware (PA), and Camden (NJ). Potentially eligible cases were Caucasian women residing in these counties at the time of diagnosis who were ages 50 to 79 years old and were newly diagnosed with breast cancer between July 1, 1999 and June 30, 2002. Controls were selected from the same geographic regions as the cases, and were frequency-matched to the cases on age (in 5-year age groups) and calendar date of interview (within 3 months). The present analysis involved 677 breast cancer cases and 905 age-matched controls who met the abovementioned criteria. Genomic DNA was obtained from buccal swabs as previously described. Genetic variants in COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1 were assayed as previously described (13). Additional details of our study design, which included ascertainment of both breast and endometrial cancer cases and matched controls, have been previously reported (11)(12)(13)(14).Odds ratio (OR) estimates and 95% confidence intervals were calculated to evaluate the relationship between hormone metabolism genes and hormone use with breast cancer risk. Using multiple conditional logistic regression, we adjusted for (a) education (

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Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer

Cited by 69 publications

References 64 publications

Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer

Lack of Effect Modification between Estrogen Metabolism Genotypes and Combined Hormone Replacement Therapy in Postmenopausal Breast Cancer Risk

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