Deciphering the folate puzzle: Unraveling the impact of genetic variations and metabolites on cancer risk.

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

Poor sleep quality association with higher lung cancer risk: a nested case-control study.

Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Body mass index is inversely associated with arterial stiffness in Chinese adults with primary hypertension: results from the China Stroke Primary Prevention Trial (CSPPT).

BACKGROUND: This study aimed to elucidate the relationship between body mass index (BMI) and the presence of arterial stiffness in rural-dwelling Chinese adults with primary hypertension. METHODS: Primary hypertension patients (n = 19,375) receiving an average of 4.5 years of antihypertension therapy were selected from the Chinese Stroke Primary Prevention Trial (mean age: 64.7 ± 7.4 years, male: 37.8%). Anthropometric, demographic, hemodynamic, and biochemical data were obtained. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV). RESULTS: BMI was inversely associated with baPWV after adjusting for gender, age, smoking, alcohol consumption, center, pulse, SBP, DBP, FBG, TC, TG, HDL-C, BUN, Scr, UA, HCY, antidiabetes treatment, lipid-lowing treatment, and antihypertensive treatment (ß (SE): -10.72 (0.69), P < 0.0001). Quintile1 (Q1) was used as a reference; Q2, Q3, Q4, and Q5 groups were all inversely associated with baPWV. The ß increased with increasing BMI, ß (SE) was -20.29 (6.74), -30.66 (7.01), -51.82 (7.27), and -103.1 (7.62), respectively, for Q2 - Q5, P < 0.05. BMI remained inversely correlated with baPWV across differences in gender, center, blood pressure, lipid levels, and the presence or absence of diabetes subgroups. CONCLUSION: Increased BMI is a positive factor against the development of arterial stiffness in Chinese rural-dwelling adults with primary hypertension undergoing antihypertension treatments, after adjusting for confounding factors.

Association between Body Mass Index and All-Cause Mortality in Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT).

The association between elevated body mass index (BMI) and risk of death has been reported in many studies. However, the association between BMI and all-cause mortality for hypertensive Chinese adults remains unclear. We conducted a post-hoc analysis using data from the China Stroke Primary Prevention Trial (CSPPT). Cox regression analysis was performed to determine the significance of the association of BMI with all-cause mortality. During a mean follow-up duration of 4.5 years, 622 deaths (3.0%) occurred among the 20,694 participants aged 45-75 years. A reversed J-shaped relationship was observed between BMI and all-cause mortality. The hazard ratios (HRs) for underweight (<18.5 kg/m²), overweight (24.0-27.9 kg/m²), and obesity (≥28.0 kg/m²) were calculated relative to normal weight (18.5-23.9 kg/m²). The summary HRs were 1.56 (95% CI, 1.11-2.18) for underweight, 0.78 (95% CI 0.64-0.95) for overweight and 0.64 (95% CI, 0.48-0.85) for obesity. In sex-age-specific analyses, participants over 60 years of age had optimal BMI in the obesity classification and the results were consistent in both males and females. Relative to normal weight, underweight was associated with significantly higher mortality. Excessive weight was not associated with increased risk of mortality. Chinese hypertensive adults had the lowest mortality in grade 1 obesity.

Effect of enalapril on plasma homocysteine levels in patients with essential hypertension.

OBJECTIVE: To investigate the effect of enalapril on plasma homocysteine (Hcy) levels and the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with the changes of Hcy levels in response to enalapril among patients with essential hypertension. METHODS: A total of 130 patients with mild-to-moderate essential hypertension were enrolled and enalapril was orally administered at a dose of 10 mg/d for eight weeks. Plasma Hcy levels were measured by denaturing high-performance liquid chromatography (DHPLC) at baseline and after eight weeks of treatment. Genotyping of MTHFR C677T polymorphism was performed by TaqMan probe technique. RESULTS: Compared with baseline, plasma Hcy levels did not change significantly after eight weeks (P=0.81). Stratified by baseline Hcy levels, a significant increase in plasma Hcy levels (P=0.02) among those with Hcy <10 micromol/L was observed, in contrast to no significant changes in plasma Hcy levels (P=0.54) among those with Hcy > or =10 micromol/L. No significant association was observed between MTHFR C677T polymorphism and changes in Hcy levels in response to enalapril. CONCLUSIONS: Enalapril may cause an increase in plasma Hcy levels among the hypertensives with low baseline Hcy levels. There was no significant association between MTHFR C677T genotypes and changes in Hcy levels in response to enalapril among subjects with essential hypertension.

Association of BDNF Val66Met polymorphism with both baseline HRQOL scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine.

OBJECTIVE: To explore the association of brain-derived neurotrophic-factor (BDNF) Val66Met polymorphism with both baseline health related quality of life (HRQOL) scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine. METHODS: Patients with major depressive disorder (MDD) took fluoxetine (20 mg/day) for 6 weeks. The HRQOL was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and at 6th week. Patients were genotyped for Val66Met polymorphism of BDNF gene. RESULTS: There was a significant association between social function (SF) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had better SF (compared with Val/Val P = 0.004; compared with Val/Met P = 0.005). A significant association was found between improvement in SF and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in SF (compared with Val/Val P = 0.010; compared with Val/Met P = 0.001). Similar association was found between improvement in mental component summary (MCS) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in MCS (compared with Val/Val P = 0.066; compared with Val/Met P = 0.006). CONCLUSIONS: These results indicate that there may be association between BDNF Val66Met polymorphism and both baseline HRQOL (SF) scores and improvement in HRQOL (SF, MCS) scores in Chinese major depressive patients treated with fluoxetine.

Association of brain-derived neurotrophic factor genetic Val66Met polymorphism with severity of depression, efficacy of fluoxetine and its side effects in Chinese major depressive patients.

BACKGROUND: Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in antidepressant action, and the BDNF gene has been suggested to be involved in the pharmacological treatment of major depressive disorder (MDD). In this study, the relationship between BDNF Val66Met polymorphism (Single Nucleotide Polymorphism Database ID: rs6265) and severity of depression, efficacy of fluoxetine and its side effects was tested in Chinese patients with MDD. METHODS: Patients with MDD took the oral selective serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg/day) for 6 weeks. Its clinical efficacy and side effects were measured by the 17-item Hamilton Rating Scale for Depression and the Treatment-Emergent Symptoms Scale (TESS), respectively. The patients were genotyped for Val66Met polymorphism of the BDNF gene. RESULTS: In the multivariate regression analysis, there was no significant association between severity of depression and BDNF Val66Met polymorphism. There was no association between efficacy of fluoxetine and BDNF Val66Met polymorphism, but there was a marginal positive suggestion that heterozygous patients tended to have a better remission with fluoxetine in comparison with homozygous analogs. Insomnia and decreased sexual desire, side effects of fluoxetine, may have an association with the BDNF Val66Met polymorphism, and Met allele carriers showed a lower incidence of these side effects. CONCLUSIONS: These results indicate that there was a lack of association between severity of depression and BDNF Val66Met polymorphism in Chinese patients with MDD. The BDNF Val66Met polymorphism may play a major role in the efficacy and side effects of SSRI (fluoxetine) in Chinese patients with MDD.