Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Int J Cancer. 2019 Nov 1;145(9):2349-2359. doi: 10.1002/ijc.32165. Epub 2019 Feb 13.
Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.
发表的饮食叶酸与膀胱癌风险之间的关联是不一致的。生物标志物可能提供更准确的营养状况衡量指标。这项嵌套病例对照分析在欧洲癌症前瞻性调查和营养研究（EPIC）中，研究了诊断前血清叶酸、同型半胱氨酸、维生素 B6 和 B12 与膀胱尿路上皮细胞癌（UCC）风险之间的关系。共 824 例新诊断的 UCC 患者与 824 名队列成员相匹配。测量了血清叶酸、同型半胱氨酸、维生素 B6 和 B12。使用条件逻辑回归，调整了吸烟状况、吸烟持续时间和强度以及其他潜在混杂因素，估计了总、侵袭性和非侵袭性 UCC 的比值比（OR）和 95%置信区间（CI）。此外，还评估了与吸烟状况的统计学交互作用。血清叶酸浓度减半与 UCC 风险中度相关（OR：1.18；95%CI：0.98-1.43），特别是侵袭性 UCC（OR：1.34；95%CI：1.02-1.75；p 异质性=0.19）。与叶酸浓度最高四分位的从不吸烟者相比，这种关联似乎仅在叶酸浓度最低四分位的当前吸烟者中明显（OR：6.26；95%CI：3.62-10.81，p 交互作用=0.07）。膳食叶酸与侵袭性 UCC 无关（OR：1.26；95%CI：0.81-1.95；p 异质性=0.14）。血清同型半胱氨酸、维生素 B6 和 B12 与 UCC 风险之间没有关联。本研究表明，较低的血清叶酸浓度与 UCC 风险增加相关，特别是侵袭性 UCC。吸烟引起的残留混杂因素不能排除，这些发现需要在未来的研究中进行多次测量以进一步证实。
