Dietary intake of nutrients involved in one‐carbon metabolism and risk of urothelial cell carcinoma: A prospective cohort study

Abstract

Nutrients involved in one-carbon metabolism may play a role in carcinogenesis through DNA replication, repair and methylation mechanisms. Most studies on urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the association between B-group vitamins and methionine intake and UCC risk, overall and by subtype, and to test whether these associations are different for population subgroups whose nutritional status may be compromised. We followed participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20 years and observed 500 UCC cases (89% originating in the bladder; superficial: 279, invasive: 221). Energy-adjusted dietary intakes of B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12) and methionine were estimated from a 121-item food frequency questionnaire administered at baseline (1990-1994), using the residuals method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk per standard deviation (SD) of log-transformed nutrient intakes and 95% confidence intervals, adjusted for potential confounders. We investigated associations by tumor subtype, and tested interactions with sex, country of birth, smoking and alcohol drinking. The risk of UCC appeared not to be associated with intake of B-group vitamins or methionine, and findings were consistent across tumor subtypes and across demographic and lifestyle characteristics of the participants. A potential interaction between vitamin B1 and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91-1.09), never drinkers: HR = 0.81 (0.69-0.97), p-interaction = 0.02), which needs to be confirmed by other studies. Our findings do not indicate that dietary intake of nutrients involved in one-carbon metabolism are associated with UCC risk.

Circulating concentrations of B group vitamins and urothelial cell carcinoma

“…Dietary studies from the MCCS have examined associations between B vitamin intakes and risk for several cancers but have only found inconsistent or weak associations. We also found no association between dietary intakes of B vitamins and UCC in our prospective cohort . These findings are in contrast to a large Spanish case–control study which reported protective associations with bladder cancer risk for B2, B6, B9 and B12 intakes.…”

“…We also found no association between dietary intakes of B vitamins and UCC in our prospective cohort. 17 These findings are in contrast to a large Spanish case-control study 14 which reported protective associations with bladder cancer risk for B2, B6, B9 and B12 intakes. Risk of recall bias and reverse causation are a potential limitation of retrospective casecontrol studies.…”

“…A Spanish case–control study reported inverse associations between B2, B6, B9 and B12 intakes and bladder cancer . A recent meta‐analysis reported an inverse association between dietary folate and bladder cancer but this finding was restricted to case–control studies and not present in cohort studies, consistent with the null association we found in a recent MCCS analysis of FFQ‐derived dietary intakes of B vitamins . Dietary measures have limitations for assessing the association between these nutrients and UCC.…”

“…14 A recent meta-analysis reported an inverse association between dietary folate and bladder cancer but this finding was restricted to case-control studies and not present in cohort studies, 15 consistent with the null association we found in a recent MCCS analysis of FFQ-derived dietary intakes of B vitamins. 17 Dietary measures have limitations for assessing the association between these nutrients and UCC. Plasma measures of B-group vitamins may provide a better exposure assessment than reported dietary intakes as the bioavailability of B-group vitamins may be compromised by some drugs, smoking and alcohol intake, 18 gut flora and absorption characteristics (e.g.…”

One‐carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

“…A meta‐analysis observed an inverse association between folate intake and bladder cancer risk in six case–control studies (OR = 0.73; 95% CI 0.57–0.89), but not in seven cohort studies (relative risk = 0.96; 95% CI 0.81–1.10) (3). Also a recent cohort study found no association of dietary intake of folate and other B‐group vitamins with UCC risk, and did not observe heterogeneity across UCC subtypes . Self‐reported dietary folate intake may be a less accurate measure of folate status than blood folate concentrations, which reflect both dietary and supplemental intakes and is directly related to bioavailability.…”