Effect of folic acid supplementation on cancer risk among adults with hypertension in C hina: A randomized clinical trial
Xianhui QinLin ShenRong ZhangYoubao LiXiaobin WangBinyan WangXiaodong JiangHua JiangLei YuFan Fan HouJin GuYong Huo
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Abstract:
The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double‐blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid( n = 10,348) or a pill containing 10 mg enalapril alone( n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril‐folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77–1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69–1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07–3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24–0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels.Keywords:
Stroke
최근에 신부전 환자들의 심혈관 질환의 발생은 혈중 호모시스테인 농도와 관련이 없고 5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T 유전자 다형성과 관련이 있다는 보고가 나오고 있다. MTHFR 유전자 다형성이 혈중 호모시스테인의 농도를 증가시킨다는 기존의 의미 외에, 그 자체로 죽상동맥경화증이나 심혈...
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Pharmacotherapy
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Objective To study the relation between polymorphisms of N 5,10 -methylenetetrahydrofolate reductase(MTHFR) and susceptibility of lung cancer.Methods We conducted a case control study with 100 cases of lung cancer and 100 population based controls in Guangdong province. MTHFR genotypes were detected by PCR-RFLP method.Results The expressions of MTHFR genotypes have a statistically significant difference between lung cancer and healthy people(P= 0.030). And there are on such difference among different gender, pathology types, and clinical stages.Conclusion The prevalence of MTHFR genotypes has a statistically significant difference between lung cancer and healthy people.
Lung cancer susceptibility
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Placebo group
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Long-term administration of angiotensin-converting—enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril.
Myocardial infarction complications
Peptidyl-Dipeptidase A
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Serum MK‐422 and plasma angiotensin converting enzyme activity were measured during the introduction of enalapril therapy in eight patients with heart failure. In a second study of 16 patients, we recorded exercise tolerance, clinical status and haemodynamics before and after 12 weeks of placebo or enalapril treatment. Increasing doses of enalapril gave step‐wise increments in serum MK‐422. Plasma converting enzyme activity remained low for at least 24 h after each dose of enalapril (5, 10 and 20 mg). Compared to placebo patients (n = 8), those receiving enalapril (n = 8) tended to improve their exercise performance and clinical status, and showed a fall in right heart pressures after 12 weeks of treatment.
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Background The methylenetetrahydrofolate reductase ( MTHFR ) polymorphism is a risk factor for neural tube defects. C677T and A1298C MTHFR polymorphisms produce an enzyme with reduced folate‐related one carbon metabolism, and this has been associated with aberrant methylation modifications in DNA and protein. Methods A meta‐analysis was conducted to assess the association between MTHFR C677T/A1298C genotypes and global genomic methylation. Results Eleven studies met the inclusion criteria. Of these, 10 were performed on C677T MTHFR genotypes and 6 were performed on A1298C MTHFR genotypes. Our results did not indicate any correlation between global methylation and MTHFR A1298C, C677T polymorphisms. Conclusion The results of our study provide evidence to assess the global methylation modification alterations of MTHFR polymorphisms among individuals. However, our data did not found any conceivable proof supporting the hypothesis that common variant of MTHFR A1298C, C677T contributes to methylation modification. Birth Defects Research (Part A) 106:667–674, 2016. © 2016 Wiley Periodicals, Inc.
genomic DNA
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Enalapril is an antihypertensive medicine that inhibits angiotensin I-converting enzyme (ACE). The present study investigated interactions between enalapril and a fermented milk product (FMP) containing the ACE-inhibitory peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP).Single-dose and long-term (6-week) in vivo studies were used to investigate the effects of enalapril and FMP on blood pressure in spontaneously hypertensive rats.Single-dose oral administration of concomitant enalapril and FMP (VPP, IPP: 3.5 mg/kg) produced a lower antihypertensive effect than enalapril monotherapy. However, this effect was not observed in animals administered a lower dose of FMP (VPP, IPP: 1.75 mg/kg) along with enalapril. In rats administered enalapril concomitantly with a fish protein product (FPP) containing a different ACE inhibitory peptide (Leu-Lys-Pro-Asn-Met), significant attenuation of the antihypertensive effect was also observed 1 and 2 h after administration, as compared to enalapril monotherapy. During a 6-week oral administration study, the enalapril monotherapy group showed significant antihypertensive effects compared to those observed in the controls on day 28. Oral administration of enalapril and FMP, with a 1-h interval between doses, resulted in significant antihypertensive effects on day 35, indicating a delayed onset in comparison to enalapril monotherapy. In rats receiving enalapril monotherapy for 28 days, followed by 14 days of concomitant FMP, significant antihypertensive effects were observed after day 35, and these did not differ significantly from the effects observed during enalapril monotherapy.The present findings suggested that long-term concomitant intake of FMP and enalapril could influence the antihypertensive effects of this drug.
Enalaprilat
Concomitant
Enalapril Maleate
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Objective To explore the relationship of the distribution of methylenetetrahydrofolate reductase enzyme(MTHFR)C677Tand A1298 Cwith lung cancer in Han population in Henan.Methods The genotype of MTHFR was detected by PCR-RFLP method in 202 cases of lung cancer(cancer group)and 202 health volunteers(control group)to analyze the gene frequency and distribution of MTHFR C677 Tand A1298C.Results The frequencies of CC,CT and TT of MTHFR C677 Twere 26.7%,50.5%and 22.8%in cancer group,and 34.2%,55.4%and 10.4%in control group,showing significant differences in TT subtype(P0.05)and no significant differences in CC and CT subtypes between two groups(P0.05).The odds ratio was 2.542 for lung cancer in those carrying TT genotype,and 95%CI was from1.453 to 4.444.The frequencies of AA,AC and CC of A1298 Cwere 27.2%,52.5%and 20.3%in cancer group,and32.2%,50.5% and 17.3% in control group,showing no significant differences between two groups(P0.05).Conclusion The TT subtype of MTHFR C677 Tgene is obviously correlated with lung cancer and A1298 Cis not correlated with lung cancer.
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