A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk

Abstract

Objective: The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk.

Design: The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values.

Setting: The meta-analysis included seventeen studies.

Subjects: A total of 10 601 patients.

Results: The non-linear dose-response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187).

Conclusions: Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.

Keywords: Colorectal cancer; Meta-analysis; Vitamin B12.

Fig. 1

Flowchart showing the literature search and study selection

Fig. 2

Dose–response relationship between vitamin B₁₂ intake and risk of colorectal cancer. Relative risks (RR; ———) and the corresponding 95 % CI (— — —) were summarized for the dose–response relationship between vitamin B₁₂ intake (μg/d) and risk of colorectal cancer. Data were modelled with random-effects restricted cubic spline models, where ---- represents the linear trend

Fig. 3

Adjusted relative risk (RR) of colorectal cancer for a wider range of vitamin B₁₂ intake (range >8 μg/d); the adjusted RR was summarized for the association between a wider range of vitamin B₁₂ intake and risk of colorectal cancer. The study-specific RR and 95 % CI are represented by the black dot and horizontal line, respectively; the area of the grey square is proportional to the specific-study weight to the overall meta-analysis. The centre of the open diamond presents the pooled RR risk and its width represents the pooled 95 % CI (NHS, Nurses’ Health Study; HPFS, Health Professionals Follow-up Study; CC, colon cancer; RC, rectal cancer)

Fig. 4

The association between sample size and the relative risk (RR) of colorectal cancer; a sampling-based scatter plot summarized the association between sample size and the RR of colorectal cancer

Fig. 5

Galbraith plot for exploring the sources of heterogeneity in the fourteen studies examining the relationship of vitamin B₁₂ intake and risk of colorectal cancer. ——— represent fitted lines; those at ±2 from the fitted (regression-through-the-origin) line represent the approximate 95 % confidence region; the studies are denoted by the first author’s surname