Carotenoid Intake and Circulating Carotenoids Are Inversely Associated with the Risk of Bladder Cancer: A Dose-Response Meta-analysis

Abstract

Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary β-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 μmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 μmol/L increase in circulating concentration of β-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 μmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary β-cryptoxanthin intake and circulating concentrations of α-carotene, β-carotene, and lutein and zeaxanthin were inversely associated with BC risk. The protocol was registered at PROSPERO as CRD42019133240.

Keywords: bladder cancer; blood; carotenoids; diet; lutein; lycopene; zeaxanthin; α-carotene; β-carotene; β-cryptoxanthin.

FIGURE 1

Flowchart of selection of studies for inclusion in the meta-analysis.

FIGURE 2

Adjusted RRs of bladder cancer for the highest compared with lowest categories of total carotenoid intake (A; 11 studies, n = 521,015)/circulating carotenoid concentrations (B; 3 studies, n = 1546) in adults. Associations were estimated using DerSimonian and Laird (15) random-effect models comparing the highest with the lowest (the referent) category.

FIGURE 3

The funnel plot for the association between dietary total carotenoid intake and the risk of bladder cancer (11 studies, n = 521,015) in adults. DerSimonian and Laird random-effect (15) models were used to generate the funnel plot. Log RR: the logarithm of the RR.

FIGURE 4

Dose-response relations between dietary intake of total carotenoids (A; n = 191,744), α-carotene (B; n = 363,092), β-carotene (C; n = 444,126), β-cryptoxanthin (D; n = 360,758), lutein and zeaxanthin (E; n = 360,758), and lycopene (F; n = 360,758) and RRs of bladder cancer in adults. Data were modeled with random-effects restricted cubic spline models with 4 knots (5^th, 35^th, 65^th, and 95^th percentiles) and using the Greenland and Longnecker method (29) to estimate the covariances of multivariable-adjusted RRs. Lines with long dashes represent the pointwise 95% CIs for the fitted nonlinear trend (solid line). Lines with short dashes represent the linear trend.

FIGURE 5

Dose-response relations between β-carotene supplementations and RRs of bladder cancer (n = 132,607) in adults. Data were modeled with random-effects restricted cubic spline models with 4 knots (5^th, 35^th, 65^th, and 95^th percentiles) and using the Greenland and Longnecker method (29) to estimate the covariances of multivariable-adjusted RRs. Lines with long dashes represent the pointwise 95% CIs for the fitted nonlinear trend (solid line). Lines with short dashes represent the linear trend.

FIGURE 6

Dose-response relations between circulating concentrations of total carotenoids (A; n = 1757), α-carotene (B; n = 2191), β-carotene (C; n = 2296), β-cryptoxanthin (D; n = 2191), lutein and zeaxanthin (E; n = 2191), and lycopene (F; n = 2296) and RRs of bladder cancer in adults. Data were modeled with random-effects restricted cubic spline models with 4 knots (5^th, 35^th, 65^th, and 95^th percentiles) and using the Greenland and Longnecker method (29) to estimate the covariances of multivariable-adjusted RRs. Lines with long dashes represent the pointwise 95% CIs for the fitted nonlinear trend (solid line). Lines with short dashes represent the linear trend.