Background Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach. Methodology and Principal Findings In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84–1.01; P = 0.076). Dose-response meta-analysis also suggested that a 100 μg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97–1.01; P = 0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100–299 μg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 μg/day). Finally, subgroup analyses of a 100 μg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women. Conclusion/Significance Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men.
References
[1]
Jemal A, Siegel R, Ward E, Hao Y, Xu J, et al. (2009) Cancer statistics, 2009. CA Cancer J Clin 59: 225–249. doi: 10.3322/caac.20006
[2]
Wingo PA, Cardinez CJ, Landis SH, Greenlee RT, Ries LA (2003) Long-term trends in cancer mortality in the United States, 1930–1998. Cancer 97: 3133–3275. doi: 10.1002/cncr.11380
[3]
Smith-Warner SA, Spiegelman D, Yaun SS, Albanes D, Beeson WL, et al. (2003) Fruits, vegetables and lung cancer: a pooled analysis of cohort studies. Int J Cancer 107: 1001–1011. doi: 10.1002/ijc.11490
[4]
Li R, Serdula M, Bland S, Mokdad A, Bowman B, et al. (2000) Trends in fruit and vegetable consumption among adults in 16 US states: behavioral risk factor surveillance system, 1990–1996. Am J Public Health 90: 777–781. doi: 10.2105/ajph.90.5.777
Selhub J, Miller JW (1991) The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55: 131–8.
[7]
Riboli E, Norat T (2003) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr 78: 559S–69S.
[8]
World Cancer Research Fund/American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective, Washington, DC: American Institute for Cancer Research.
[9]
Voorrips LE, Goldbohm RA, Brants HAM, van Poppel GA, Sturmans F, et al. (2000) A Prospective Cohort Study on Antioxidant and Folate Intake and Male Lung Cancer Risk. Cancer Epidemiol Biomarkers Prev 9: 357–365.
[10]
Hartman TJ, Woodson K, Stolzenberg-Solomon R, Virtamo J, Selhub J, et al. (2001) Association of the B-Vitamins Pyridoxal 5′-Phosphate (B6), B12, and Folate with Lung Cancer Risk in Older Men. Am J Epidemiol 153: 688–94. doi: 10.1093/aje/153.7.688
[11]
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) PRISMA Group (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Plos Medicine 6: e1000097. doi: 10.1371/journal.pmed.1000097
[12]
Wells G, Shea B, O'Connell D (2009) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa (ON): Ottawa Hospital Research Institute. Available:http://www.ohri.ca/programs/clinical_epi?demiology/oxford.htm.
[13]
Higgins JP, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. Available: www.cochrane-handbook.org.
[14]
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–88. doi: 10.1016/0197-2456(86)90046-2
[15]
Ades AE, Lu G, Higgins JP (2005) The interpretation of random-effects metaanalysis in decision models. Med Decis Making 25: 646–54. doi: 10.1177/0272989x05282643
[16]
Orsini N, Bellocco R (2006) Generalized least squares for trend estimation of summarized dose-response data. Stata J 2006 6: 40–57.
[17]
Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135: 1301–09.
[18]
Deeks JJ, Higgins JPT, Altman DG (2008) Analyzing data and undertaking meta-analyses. In: Higgins J, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions 5.0.1. Oxford, UK: The Cochrane Collaboration: chap 9.
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–34. doi: 10.1136/bmj.315.7109.629
[21]
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50: 1088–1101. doi: 10.2307/2533446
[22]
Bandera EV, Freudenheim JL, Marshall JR, Zielezny M, Priore RL, et al. (1997) Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States). Cancer Causes and Control 8: 828–840. doi: 10.1023/a:1018456127018
[23]
Yuan JM, Stram DO, Arakawa K, Lee HP, Yu MC (2003) Dietary Cryptoxanthin and Reduced Risk of Lung Cancer: The Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 12: 890–898.
[24]
Slatore CG, Littman AJ, Au DH, Satia JA, White E (2008) Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer. Am J Respir Crit Care Med 177: 524–530. doi: 10.1164/rccm.200709-1398oc
[25]
Kabat GC, Miller AB, Jain M, Rohan TE (2008) Dietary intake of selected B vitamins in relation to risk of major cancers in women. Br J Cancer 99: 816–821.
[26]
Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, et al. (2010) Source-specific effects of micronutrients in lung cancer prevention. Lung Cancer 67: 275–281. doi: 10.1016/j.lungcan.2009.11.010
[27]
Bassett JK, Hodge AM, English DR, Baglietto L, Hopper JL, et al. (2012) Dietary intake of B vitamins and methionine and risk of lung cancer. Eur J Clin Nutr 66: 182–187. doi: 10.1038/ejcn.2011.157
[28]
Takata Y, Cai Q, Beeghly-Fadiel A, Li H, Shrubsole MJ, et al. (2012) Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China. Cancer Causes Control 23: 1965–75. doi: 10.1007/s10552-012-0074-z
[29]
Takata Y, Xiang YB, Yang G, Li H, Gao J, et al. (2013) Intakes of Fruits, Vegetables, and Related Vitamins and Lung Cancer Risk: Results from the Shanghai Men's Health Study (2002–2009). Nutr Cancer 65: 51–61. doi: 10.1080/01635581.2013.741757
[30]
Shen H, Wei Q, Pillow PC, Amos CI, Hong WK, et al. (2003) Dietary folate intake and lung cancer risk in former smokers: a case-control analysis. Cancer Epidemiol Biomarkers Prev 12: 980–986.
[31]
Shi Q, Zhang Z, Neumann AS, Li G, Spitz MR, et al. (2005) Case-control analysis of thymidylate synthase polymorphisms and risk of lung cancer. Carcinogenesis 26: 649–656. doi: 10.1093/carcin/bgh351
[32]
Hung RJ, Hashibe M, McKay J, Gaborieau V, Szeszenia-Dabrowska N, et al. (2007) Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis 28: 1334–1340. doi: 10.1093/carcin/bgm067
[33]
Le Marchand L, Yoshizawa CN, Kolonel LN, Hankin JH, Goodman MT (1989) Vegetable consumption and lung cancer risk: a population-based case-control study in Hawaii. J Natl Cancer Inst 81: 1158–1164. doi: 10.1093/jnci/81.15.1158
[34]
Suzuki T, Matsuo K, Hiraki A, Saito T, Sato S, et al. (2007) Impact of one-carbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case control study. Carcinogenesis 28: 1718–1725. doi: 10.1093/carcin/bgm104
[35]
Vaissiere T, Hung RJ, Zaridze D, Moukeria A, Cuenin C, et al. (2009) Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors. Cancer Res 69: 243–252. doi: 10.1158/0008-5472.can-08-2489
[36]
Cho E, Hunter DJ, Spiegelman D, Albanes D, Beeson WL, et al. (2006) Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: A pooled analysis of 8 prospective studies. Int J Cancer 118: 970–978. doi: 10.1002/ijc.21441