1. Humans and animals are commonly exposed to indole-3-carbinol (I3C) and resveratrol (RES) via food or beverages. Moreover, these compounds have been demonstrated to potentially cause food-drug interactions. However, information about their combined effects is limited. Therefore, we investigated the effects of I3C and RES, both as single compounds and in combination, on cytochrome P450 1A and 3A activity and gene expression. 2. Using porcine microsomes, we demonstrated that RES caused non-competitive inhibition of CYP1A activity and un-competitive inhibition of CYP3A activity. Compared to the effect of single compounds, co-treatment with I3C and RES increased a degree of inhibition of CYP1A activity. 3. In porcine primary hepatocytes, treatment with I3C and RES resulted in induction of CYP1A1, CYP1A2 and CYP3A29 mRNA expression. 4. In conclusion, we demonstrated that both RES and I3C could cause food-drug interactions and that the combined effect could be more potent in doing so.

• Klíčová slova
• Detoxification, food–drug, gene-regulation, liver, secondary plant metabolites,
• MeSH
• cytochrom P-450 CYP1A1 antagonisté a inhibitory   metabolismus   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• hepatocyty účinky léků   MeSH
• indoly farmakologie   MeSH
• inhibitory cytochromu P450 CYP3A farmakologie   MeSH
• interakce mezi potravou a léky MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• prasata MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků genetika   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• resveratrol MeSH
• steroidní receptory genetika   MeSH
• stilbeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P-450 CYP3A MeSH
• indole-3-carbinol MeSH Prohlížeč
• indoly MeSH
• inhibitory cytochromu P450 CYP3A MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků MeSH
• resveratrol MeSH
• steroidní receptory MeSH
• stilbeny MeSH

The effects of clotrimazole (CLO) and dexamethasone (DEX), both detected in the aquatic environment, were assessed on inhibition of cytochrome P450 (CYP450) in hepatic microsomes of rainbow trout. Activity of three CYP450 isoforms: ethoxyresorufin O-deethylase (EROD; CYP1A), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD; CYP3A) and p-nitrophenol hydroxylase (PNPH; CYP2E1-like protein) was investigated in the presence of four concentrations of CLO and DEX. Clotrimazole in a concentration range of 1-100μM decreased the activity of EROD and BFCOD. The inhibition was reversible, as pre-incubation of the microsomes with CLO, before addition of the substrate, had no effect. EROD activity was non-competitively inhibited with a Ki of 0.5μM, and BFCOD activity revealed competitive inhibition with a Ki of 0.04μM. The relatively low Ki for CLO inhibition of EROD and BFCOD activity may indicate that the ability of CYP1A and CYP3A to metabolize xenobiotics is reduced in the presence of CLO. PNPH activity was not affected by CLO. DEX showed no inhibitory potency on any investigated reaction. CLO, but not DEX, inhibited EROD and BFCOD activity by different mechanisms.

• Klíčová slova
• 7-benzyloxy-4-trifluoromethylcoumarin, 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase, 7-benzyloxyquinoline, BFC, BFCOD, BQ, BzRes, CLO, CYP1A, CYP2E1-like protein, CYP3A, Clotrimazole, DBF, DEX, Dexamethasone, EROD, P450, PNP, PNPH, Rainbow trout, benzyloxyresorufin, clotrimazole, cytochrome P450, dexamethasone, dibenzylfluorescein, ethoxyresorufin O-deethylase, p-nitrophenol, p-nitrophenol hydroxylase,
• MeSH
• cytochrom P-450 CYP1A1 antagonisté a inhibitory   metabolismus   MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• dexamethason chemie   farmakologie   MeSH
• inhibitory cytochromu P450 CYP2E1 MeSH
• inhibitory cytochromu P450 CYP3A MeSH
• inhibitory cytochromu P450 MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• kinetika MeSH
• klotrimazol chemie   farmakologie   MeSH
• Oncorhynchus mykiss metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P-450 CYP2E1 MeSH
• cytochrom P-450 CYP3A MeSH
• dexamethason MeSH
• inhibitory cytochromu P450 CYP2E1 MeSH
• inhibitory cytochromu P450 CYP3A MeSH
• inhibitory cytochromu P450 MeSH
• klotrimazol MeSH
• systém (enzymů) cytochromů P-450 MeSH

UNLABELLED: The present work was designed to determine whether the individual differences in pharmacokinetics and pharmacodynamics of amiodarone and its N-desethyl metabolite are related to cytochrome CYP3A metabolizer status. METHODS: 12 cardiac patients with inducible ventricular tachyarrhythmias during the baseline electrophysiologic study were enrolled in this study. Urinary 24-hour excretion of 6 beta-hydroxycortisol (6 beta-OHC and the ratio of 6 beta-hydroxycortisol to urinary free cortisol (6 beta-OHC/UFC) were measured before the first amiodarone administration. Trough plasma concentrations of amiodarone and N-desethylamiodarone (N-DEA) were measured after 79 +/- 11 days (2nd period) and after 182 +/- 25 days (3rd period). Electrophysiologic effects of amiodarone therapy were established with serial electrophysiologic studies in 9 of these patients at the baseline and after 79 +/- 11 days (during the second period). RESULTS: Both the 6 beta-OHC excretion and 6 beta-OHC/UFC ratio varied approximately 6-fold between the patients. We found significant inverse correlation between the 6 beta-OHC excretion and the trough plasma concentrations of amiodarone at the time of the 3rd period (rs = -0.58, p < 0.05). Similarly, there was correlation between the 24-hour urinary 6 beta-OHC excretion and trough plasma concentrations of amiodarone during the 3rd period (rs = -0.64, p < 0.025). We were unable to detect any association between CYP3A activity and amiodarone pharmacodynamics. CONCLUSION: This study points toward important information value of CYP3A metabolizer status in the context of therapeutic drug monitoring of amiodarone.

• MeSH
• amiodaron analogy a deriváty   farmakokinetika   MeSH
• antiarytmika farmakokinetika   MeSH
• aromatické hydroxylasy * MeSH
• cytochrom P-450 CYP3A MeSH
• dospělí MeSH
• elektrofyziologické techniky kardiologické MeSH
• hydrokortison analogy a deriváty   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• N-demethylasy metabolismus   MeSH
• senioři MeSH
• srdeční arytmie farmakoterapie   metabolismus   patofyziologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 6 beta-hydroxycortisol MeSH Prohlížeč
• amiodaron MeSH
• antiarytmika MeSH
• aromatické hydroxylasy * MeSH
• cytochrom P-450 CYP3A MeSH
• hydrokortison MeSH
• N-demethylasy MeSH
• systém (enzymů) cytochromů P-450 MeSH

Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants (CYP3A4*22/CYP3A5*3) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (<5 ng/ml). Multivariate Cox regression analyses revealed that CYP3A HM1 and IM pharmacogenetic phenotypes (hazard ratio (HR) 12.566, 95% CI 1.99-79.36, p = 0.007, and HR 4.532, 95% CI 1.10-18.60, p = 0.036, respectively), preformed DSTs (HR 3.482, 95% CI 1.99-6.08, p < 0.001), DSAs (HR 4.421, 95% CI 1.63-11.98, p = 0.003), and delayed graft function (DGF) (HR 2.023, 95% CI 1.22-3.36, p = 0.006) independently predicted BPAR. Notably, a significant interaction between T-cell depletion and TAC underexposure was observed, showing a reduction of the BPAR risk (HR 0.264, 95% CI 0.08-0.92, p = 0.037). Such variables except for DSAs displayed a higher predictive risk for the development of T cell-mediated rejection (TCMR). Refinement of pretransplant monitoring by incorporating TAC CYP3A SNPs with preformed DSAs as well as DSTs may improve current rejection-risk stratification and help induction treatment decision-making.

• Klíčová slova
• acute rejection, calcineurin inhibitors immunosuppression, genetics, immunobiology, kidney transplantation,
• MeSH
• cytochrom P-450 CYP3A * genetika   imunologie   metabolismus   MeSH
• hodnocení rizik MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• paměťové B-buňky * imunologie   MeSH
• T-lymfocyty * imunologie   MeSH
• takrolimus * farmakologie   terapeutické užití   MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CYP3A protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A * MeSH
• takrolimus * MeSH

Amlodipine (AML) is available as a racemate, i.e., a mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug-drug interactions between the enantiomers. Enzyme inhibition was evaluated using specific CYP substrates in human liver microsomes. With CYP3A, both enantiomers exhibited reversible and time-dependent inhibition. S-AML was a stronger reversible inhibitor of midazolam hydroxylation: the Ki values of S- and R-AML were 8.95 µM, 14.85 µM, respectively. Computational docking confirmed that the enantiomers interact differently with CYP3A: the binding free energy of S-AML in the active site was greater than that for R-AML (-7.6- vs. -6.7 kcal/mol). Conversely, R-AML exhibited more potent time-dependent inhibition of CYP3A activity (KI 8.22 µM, Kinact 0.065 min-1) than S-AML (KI 14.06 µM, Kinact 0.041 min-1). R-AML was also a significantly more potent inhibitor of CYP2C9 (Ki 12.11 µM/S-AML 21.45 µM) and CYP2C19 (Ki 5.97 µM/S-AML 7.22 μM. In conclusion, results indicate that clinical use of S-AML has an advantage not only because of greater pharmacological effect, but also because of fewer side effects and drug-drug interactions with cytochrome P450 substrates due to absence of R-AML.

• Klíčová slova
• amlodipine, cytochrome P450, drug–drug interactions, enantiomers, enzyme inhibition, stereoselectivity,
• MeSH
• amlodipin chemie   farmakologie   MeSH
• hydroxylace MeSH
• inhibitory cytochromu P450 CYP3A chemie   farmakologie   MeSH
• inhibitory cytochromu P450 chemie   farmakologie   MeSH
• jaterní mikrozomy metabolismus   MeSH
• kinetika MeSH
• lékové interakce MeSH
• lidé MeSH
• midazolam metabolismus   MeSH
• molekulární struktura MeSH
• simulace molekulového dockingu MeSH
• stereoizomerie MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• termodynamika MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amlodipin MeSH
• inhibitory cytochromu P450 CYP3A MeSH
• inhibitory cytochromu P450 MeSH
• midazolam MeSH
• systém (enzymů) cytochromů P-450 MeSH

This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNA-expressed CYP2E1 with the Ki=52.1±6.31μM. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki=15.4±1.52μM, and myricetin - noncompetitively with the Ki=74.6±7.99μM. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender-dependent.

• Klíčová slova
• Cytochrome P450, Females, Flavonols, Hepatic microsomes, Males, isorhamnetin (PubChem CID: 5281654), myricetin (PubChem CID: 5281672), quercetin (PubChem CID: 5280343),
• MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• hydroxylace MeSH
• inhibitory cytochromu P450 CYP2E1 farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• kumariny metabolismus   MeSH
• lidé MeSH
• nitrofenoly metabolismus   MeSH
• quercetin analogy a deriváty   farmakologie   MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-methylquercetin MeSH Prohlížeč
• 4-nitrophenol MeSH Prohlížeč
• 7-benzyloxy-4-trifluoromethylcoumarin MeSH Prohlížeč
• cytochrom P-450 CYP2E1 MeSH
• cytochrom P-450 CYP3A MeSH
• flavonoidy MeSH
• inhibitory cytochromu P450 CYP2E1 MeSH
• inhibitory enzymů MeSH
• kumariny MeSH
• myricetin MeSH Prohlížeč
• nitrofenoly MeSH
• quercetin MeSH

The anticoagulant drug warfarin is used treat atrial fibrillation. Several cases of drug-drug and drug-food interactions have been reported for warfarin.The aim of this study was to investigate the interaction between simultaneous administration of warfarin with the two ubiquitous flavonoids quercetin and curcumin.Using porcine primary hepatocytes we demonstrated that warfarin treatment increased the mRNA and protein expression of CYP3A(29), while no changes in CYP1A2 were observed. Co-treatment with quercetin and/or curcumin decreased the warfarin-induced CYP3A protein expression. Moreover, when quercetin and curcumin were co-administrated to warfarin-exposed hepatocytes the protein expression of CYP1A2 was decreased. In hepatic microsomes, curcumin inhibited the activity of both CYP1A2 and CYP3A, while warfarin had no effect. Both quercetin and curcumin decreased the CYP1A2 and CYP3A activity when co-administrated with warfarin.The results clearly demonstrated that quercetin and curcumin can cause food-drug interactions with warfarin, and that the cocktail effect of exposure to more compounds than one can further enhance these interactions.

• Klíčová slova
• Liver, cytochrome p450, drug metabolism, food–drug interactions, in vitro, plant secondary metabolites,
• MeSH
• cytochrom P-450 CYP1A2 * MeSH
• cytochrom P-450 CYP3A MeSH
• jaterní mikrozomy MeSH
• kurkumin * MeSH
• prasata MeSH
• quercetin MeSH
• systém (enzymů) cytochromů P-450 MeSH
• warfarin MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochrom P-450 CYP1A2 * MeSH
• cytochrom P-450 CYP3A MeSH
• kurkumin * MeSH
• quercetin MeSH
• systém (enzymů) cytochromů P-450 MeSH
• warfarin MeSH

This study examined the ability of several human pharmaceuticals to modulate hepatic piscine CYP-mediated monooxygenase activities. Effects of six pharmaceuticals: diclofenac, sulfamethoxazole, tramadol, carbamazepine, venlafaxine and nefazodone, were investigated in vitro in rainbow trout hepatic microsomes. The reactions of 7-ethoxyresorufin-O-deethylase (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylase (BFCOD), were used as markers for hepatic CYP1A and CYP3A-like activities, respectively. Our results showed that EROD and BFCOD activities were both affected by nefazodone. Nefazodone inhibited EROD in a dose dependent manner and was found to be a potent non-competitive inhibitor of EROD with a Ki value of 6.6 μM. BFCOD activity was inhibited non-competitively in the presence of nefazadone with Ki value of 30.7 μM. BFCOD activity was slightly reduced only by the highest concentration of carbamazepine. Diclofenac, sulfamethoxazole, tramadol, and venlafaxine did not affect the activity of either EROD or BFCOD. We further exposed microsomal fraction to mixtures of six pharmaceuticals to investigate potential inhibition. The results showed that EROD and BFCOD activity was inhibited on 94% and 80%, respectively at higher tested concentration. To our knowledge, this is the first report to demonstrate an inhibitory effect of nefazodone on hepatic CYP1A and CYP3A-like proteins in rainbow trout.

• Klíčová slova
• Antidepressant, Cytochrome P450, Fish microsomes, Inhibition, Mixture of compounds,
• MeSH
• chemické látky znečišťující vodu MeSH
• cytochrom P-450 CYP1A1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• jaterní mikrozomy enzymologie   metabolismus   MeSH
• játra metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• Oncorhynchus mykiss metabolismus   MeSH
• piperaziny MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P-450 CYP3A MeSH
• léčivé přípravky MeSH
• nefazodone MeSH Prohlížeč
• piperaziny MeSH
• triazoly MeSH

The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin with Ki values from 1.7 to 2.6 μM. BROD activity was inhibited by quercetin with Ki values from 64.9 to 75.3 μM and naringenin with Ki values from 39.3 to 45.8 μM. The IC50 and Ki values did not differ between the groups of mice with different levels of POPs exposure in any of the experimental sets. Sesamin did not inhibit either EROD or BROD. We concluded that the interactions of quercetin and naringenin with CYP1A and CYP3A in mice liver were not affected by the levels of POPs exposure.

• MeSH
• cytochrom P-450 CYP3A MeSH
• dioxoly farmakologie   MeSH
• flavanony farmakologie   MeSH
• jaterní mikrozomy enzymologie   patologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lignany farmakologie   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• myši MeSH
• quercetin farmakologie   MeSH
• rodina 1 cytochromu P450 metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   enzymologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CYP3A protein, mouse MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• dioxoly MeSH
• flavanony MeSH
• látky znečišťující vzduch MeSH
• lignany MeSH
• naringenin MeSH Prohlížeč
• quercetin MeSH
• rodina 1 cytochromu P450 MeSH
• sesamin MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29). CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

• MeSH
• běloši MeSH
• cytochrom P-450 CYP3A genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie * MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• menarche genetika   MeSH
• nádory prsu genetika   patologie   MeSH
• premenopauza genetika   MeSH
• reprodukční anamnéza MeSH
• rizikové faktory MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• cytochrom P-450 CYP3A MeSH