Vitamin B2 intake reduces the risk for colorectal cancer: a dose–response analysis
Several epidemiological studies have assessed the ability of vitamin B2 to prevent colorectal cancer (CRC), but the results are controversial results. We conducted a dose–response meta-analysis to investigate the association between vitamin B2 and CRC risk.
We searched the PubMed and EMBASE database until January 3, 2018 to identify relevant studies. The pooled relative risks (RRs) with the corresponding 95% confidence intervals (CIs) were calculated using a random-effects model or fixed-effects model. The dose–response relationship was assessed by restricted cubic splines.
A total of 14 studies reporting vitamin B2 intake and two studies reporting blood vitamin B2 concentration, comprising 14,934 cases and 1593 cases, respectively, were included in the meta-analysis. Vitamin B2 intake was inversely associated with CRC risk (RR = 0.87; 95% CI 0.81–0.93). Similar results were found for total vitamin B2 intake from diet and supplements (RR = 0.86; 95% CI 0.78–0.94) and dietary vitamin B2 intake (RR = 0.89, 95% CI 0.82–0.98) in subgroup analyses. The dose–response model indicated a non-linear trend, and CRC risk was reduced by 10% when vitamin B2 intake increased to 5 mg/day. In addition, high blood concentrations of vitamin B2 could also reduce the CRC risk (RR = 0.74; 95% CI 0.59–0.92).
This dose–response analysis indicates that vitamin B2 intake is inversely associated with CRC risk. The inverse association may also exist between blood vitamin B2 concentration and CRC risk. These results suggest the importance of vitamin B2 intake in the prevention of CRC.
KeywordsColorectal cancer Vitamin B2 Dose–response Meta-analysis
Conception and design: Meilin Wang, Dongying Gu, and Yuan Wu; Development of methodology: Shuai Ben, Mulong Du, and Gaoxiang Ma; Acquisition of data: Haiyan Chu and Liyang Zhu; Administrative, technical, or material support: Jianhua Qu and Zhengdong Zhang; Study supervision: Meilin Wang, Dongying Gu, and Yuan Wu.
This work was supported by the National Key R&D Program of China (2017YFC0908200), the National Natural Science Foundation of China (81773516), Distinguished Young Scholars of Nanjing (JQX13005), the Qinlan Project of Jiangsu (Meilin Wang), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 8.Powers HJ (2003) Riboflavin (vitamin B-2) and health. Am J Clin Nutr 77(6):1352–1360Google Scholar
- 9.Rivlin RS (1973) Riboflavin and cancer: a review. Cancer Res 33(9):1977–1986Google Scholar
- 11.Strohle A, Wolters M, Hahn A (2005) Folic acid and colorectal cancer prevention: molecular mechanisms and epidemiological evidence (Review). Int J Oncol 26(6):1449–1464Google Scholar
- 12.La Vecchia C, Braga C, Negri E, Franceschi S, Russo A, Conti E, Falcini F, Giacosa A, Montella M, Decarli A (1997) Intake of selected micronutrients and risk of colorectal cancer. Int J Cancer 73(4):525–530Google Scholar
- 13.Sun Z, Zhu Y, Wang PP, Roebothan B, Zhao J, Zhao J, Dicks E, Cotterchio M, Buehler S, Campbell PT, McLaughlin JR, Parfrey PS (2012) Reported intake of selected micronutrients and risk of colorectal cancer: results from a large population-based case–control study in Newfoundland, Labrador and Ontario, Canada. Anticancer Res 32(2):687–696Google Scholar
- 14.Shrubsole MJ, Yang G, Gao Y-T, Chow WH, Shu XO, Cai Q, Rothman N, Gao J, Wagner C, Zheng W (2009) Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women. Cancer Epidemiol Prev Biomark 18(3):1003–1006Google Scholar
- 15.Jedrychowski W, Steindorf K, Popiela T, Wahrendorf J, Tobiasz-Adamczyk B, Kulig J, Penar A (2001) Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case–control study in Poland. Rev Environ Health 16(3):213–222Google Scholar
- 16.Otani T, Iwasaki M, Hanaoka T, Kobayashi M, Ishihara J, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Yoshimura K, Yoshida T, Tsugane S (2005) Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case–control study in Japan. Nutr Cancer 53(1):42–50. https://doi.org/10.1207/s15327914nc5301_5 Google Scholar
- 17.Liu Y, Yu QY, Zhu ZL, Tang PY, Li K (2015) Vitamin B2 intake and the risk of colorectal cancer: a meta-analysis of observational studies. Asian Pac J Cancer Prev 16(3):909–913Google Scholar
- 18.Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605Google Scholar
- 19.DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controll Clin Trials 7(3):177–188Google Scholar
- 20.Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748Google Scholar
- 21.Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280(19):1690–1691Google Scholar
- 23.Hedges LV, Pigott TD (2001) The power of statistical tests in meta-analysis. Psychol Methods 6(3):203–217Google Scholar
- 25.Harrell FE Jr, Lee KL, Pollock BG (1988) Regression models in clinical studies: determining relationships between predictors and response. J Natl Cancer Inst 80(15):1198–1202Google Scholar
- 27.Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309Google Scholar
- 28.Thornton A, Lee P (2000) Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol 53(2):207–216Google Scholar
- 29.Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634Google Scholar
- 31.Zschabitz S, Cheng TY, Neuhouser ML, Zheng Y, Ray RM, Miller JW, Song X, Maneval DR, Beresford SA, Lane D, Shikany JM, Ulrich CM (2013) B vitamin intakes and incidence of colorectal cancer: results from the Women’s Health Initiative Observational Study cohort. Am J Clin Nutr 97(2):332–343. https://doi.org/10.3945/ajcn.112.034736 Google Scholar
- 34.Sharp L, Little J, Brockton NT, Cotton SC, Masson LF, Haites NE, Cassidy J (2008) Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case–control study in a population with relatively low folate intake. Br J Nutr 99(2):379–389. https://doi.org/10.1017/S0007114507801073 Google Scholar
- 36.van Lee L, Heyworth J, McNaughton S, Iacopetta B, Clayforth C, Fritschi L (2011) Selected dietary micronutrients and the risk of right- and left-sided colorectal cancers: a case–control study in Western Australia. Ann Epidemiol 21(3):170–177. https://doi.org/10.1016/j.annepidem.2010.10.005 Google Scholar
- 37.Key TJ, Appleby PN, Masset G, Brunner EJ, Cade JE, Greenwood DC, Stephen AM, Kuh D, Bhaniani A, Powell N, Khaw KT (2012) Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium. Int J Cancer 131(3):E320–325. https://doi.org/10.1002/ijc.27386 Google Scholar
- 38.Morita M, Yin G, Yoshimitsu S, Ohnaka K, Toyomura K, Kono S, Ueki T, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Maekawa T, Yasunami Y, Takenaka K, Ichimiya H, Terasaka R (2013) Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study. Asian Pac J Cancer Prev 14(11):6249–6256Google Scholar
- 39.Weinstein SJ, Albanes D, Selhub J, Graubard B, Lim U, Taylor PR, Virtamo J, Stolzenberg-Solomon R (2008) One-carbon metabolism biomarkers and risk of colon and rectal cancers. Cancer Epidemiol Prev Biomark 17(11):3233–3240Google Scholar
- 40.Eussen SJ, Vollset SE, Hustad S, Midttun O, Meyer K, Fredriksen A, Ueland PM, Jenab M, Slimani N, Boffetta P, Overvad K, Thorlacius-Ussing O, Tjonneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Weikert C, Pischon T, Linseisen J, Kaaks R, Trichopoulou A, Zilis D, Katsoulis M, Palli D, Pala V, Vineis P, Tumino R, Panico S, Peeters PH, Bueno-de-Mesquita HB, van Duijnhoven FJ, Skeie G, Munoz X, Martinez C, Dorronsoro M, Ardanaz E, Navarro C, Rodriguez L, VanGuelpen B, Palmqvist R, Manjer J, Ericson U, Bingham S, Khaw KT, Norat T, Riboli E (2010) Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 19(10):2549–2561. https://doi.org/10.1158/1055-9965.epi-10-0407
- 41.Otten JJ, Hellwig JP, Meyers LD (2006) Dietary reference intakes: the essential guide to nutrient requirements. National Academies PressGoogle Scholar
- 43.Webster RP, Gawde MD, Bhattacharya RK (1996) Modulation of carcinogen-induced DNA damage and repair enzyme activity by dietary riboflavin. Cancer Lett 98(2):129–135Google Scholar
- 44.Ulrich CM (2005) Nutrigenetics in cancer research–folate metabolism and colorectal cancer. J Nutr 135(11):2698–2702Google Scholar
- 46.Agnoli C, Grioni S, Krogh V, Pala V, Allione A, Matullo G, Di Gaetano C, Tagliabue G, Pedraglio S, Garrone G, Cancarini I, Cavalleri A, Sieri S (2016) Plasma riboflavin and vitamin B-6, but not homocysteine, folate, or vitamin B-12, are inversely associated with Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort. J Nutr 146(6):1227–1234. https://doi.org/10.3945/jn.115.225433 Google Scholar
- 47.Akimoto M, Sato Y, Okubo T, Todo H, Hasegawa T, Sugibayashi K (2006) Conversion of FAD to FMN and riboflavin in plasma:effects of measuring method. Biol Pharm Bull 29(8):1779–1782Google Scholar