Effect of folic acid supplementation on cancer risk among adults with hypertension in <scp>C</scp>hina: A randomized clinical trial

Qin, Xianhui; Shen, Lin; Zhang, Rong; Li, Youbao; Wang, Xiaobin; Zhang, Yuanyuan; Jiang, Xiaodong; Hua, Jian; Lei, Yu; Hou, Fan Fan; Gu, Jin; Huo, Yong

doi:10.1002/ijc.30094

Cited by 26 publications

(18 citation statements)

References 40 publications

(99 reference statements)

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“…Due to a limited number of cases, we did not have enough statistical power to verify our hypothesis. In our recent publication from the same cohort, we found that folic acid supplementation did not reduce cancer risk in the whole study population, but there was a reduction in cancer risk in participants with the MTHFR C677T genotype accompanied with low baseline folate levels. A meta‐analysis concluded that women with daily dietary folate intake between 153 and 400 μg showed a significantly reduced breast cancer risk compared with those whose folate intake was <153 μg, but not for those whose intake was >400 μg.…”

Section: Discussionmentioning

confidence: 73%

Association of serum uric acid with increased risk of cancer among hypertensive Chinese

Yang

Wang

Zhao

et al. 2017

Intl Journal of Cancer

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Several large prospective studies show an association between serum uric acid (SUA) and cancer, however there is a lack of evidence in China. We aimed to investigate the effects of SUA levels on cancer incidence and mortality in China. This study included 20,577 adult hypertensive patients with valid SUA measurements who participated in the China Stroke Primary Prevention Trial where subjects were randomly assigned to receive a double-blind treatment of either 10 mg enalapril (n = 10,286) or 10.8 mg enalapril-folic acid (n = 10,291). Subjects were prospectively followed for a median of 4.5 years. Cox proportional hazards models were used to calculate hazards ratios (HR) of cancer risk associated with SUA. A total of 232 participants developed cancer. SUA was independently associated with increased cancer risk in the enalapril group [HR: 1.12, (95% CI: 1.03-1.22)]. Compared to the lowest tertile, combined subjects with SUA levels from the upper two tertiles had a higher risk of cancer in the enalapril group [T2 + T3: HR: 1.58, (95% CI: 1.02-2.47)]. In cancer site-specific analyses, a positive association of SUA levels with digestive cancer and all fatal cancer was also observed [HR: 1.18, (95% CI: 1.09-1.27); HR: 1.15, (95% CI: 1.03-1.28), respectively] in the enalapril group. Interestingly, SUA levels were not associated with the risk of cancer or related mortality in the enalapril folic acid group. Our results suggest that elevated SUA is independently and positively associated with the risk of total cancer incidence, digestive cancer incidence and cancer mortality among hypertensive Chinese.

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Section: Discussionmentioning

confidence: 73%

Association of serum uric acid with increased risk of cancer among hypertensive Chinese

Yang

Wang

Zhao

et al. 2017

Intl Journal of Cancer

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“…A recent study suggested that the effect of folic acid may depend upon the existing level of blood folate along with methylenetetrahydrofolate reductase (MTHFR) genotype. 74 Therefore, the effect of folic acid on CRC may require further investigation based on those factors.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: systematic review and network meta-analysis

Veettil

Jinatongthai

Nathisuwan

et al. 2018

CLEP

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BackgroundVarious interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality.MethodsWe did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality.ResultsTwenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57–0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67–0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23–0.81] for low-dose [>100–325 mg/day] and RR, 0.65 [95% CI, 0.45–0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010–2.434].ConclusionAspirin at the dose range of 75–325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.

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“…Moreover, enalapril-folic acid therapy, compared with enalapril alone, can significantly delay the progression of chronic kidney diseases among hypertensive patients with mild-to-moderate chronic kidney diseases (29) , and reduce the mortality risk in hypertensive patients with heavy proteinuria (30) , the development of proteinuria in diabetic patients with hypertension (31) , and the magnitude of the increase of uric acid concentrations in general hypertensive adults (32) . However, enalapril-folic acid therapy had no significant effect on the risk of new-onset diabetes (33) or cancer (34) , compared with enalapril alone. In addition, our previous study suggested that elevated tHcy concentrations significantly decreased the antihypertensive effect of the enalapril-based antihypertensive treatment in previously untreated hypertensive patients (35) .…”

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confidence: 87%

Association of plasma retinol levels with incident cancer risk in Chinese hypertensive adults: a nested case–control study

et al. 2019

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We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case–control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2–4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose–response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).

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Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial

Cited by 26 publications

References 40 publications

Association of serum uric acid with increased risk of cancer among hypertensive Chinese

Association of serum uric acid with increased risk of cancer among hypertensive Chinese

Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: systematic review and network meta-analysis

Association of plasma retinol levels with incident cancer risk in Chinese hypertensive adults: a nested case–control study

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