Please wait a minute...
93TMR Cancer  2019, Vol. 2 Issue (4): 252-260    DOI: 10.12032/TMRC201800054
Cancer Biology     
Null links between vitamin B6 and B12 intake and occurrence risk of lung cancer: a meta-analysis
Li-Ping Shen1, Rong Li2, Ya-Juan Cao3,*()
1Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200073, China.
2Liuzhou Traditional Chinese Medicine Hospital, Guangxi 545000, China.
3Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Download: HTML     PDF(879KB)
Export: BibTeX | EndNote (RIS)      

Highlights

Vitamin B6 and vitamin B12 are coenzyme involved in the complex one-carbon metabolism pathway.

The relationship between vitamin B6 and B12 intake and occurrence risk of lung cancer remains controversial.

Comments

Vitamin B6 and vitamin B12 are considered play an important role in the DNA integrity maintenance, gene expression regulation, supply of methyl groups, and the growth and repair of cells, and disruption of this process may promote carcinogenesis, which may play an essential role in tumor progression.

Abstract

Vitamin B6 and B12 are involved in many biochemical reactions and might play a role in carcinogenesis. We summarized the evidences linking vitamin B6 and B12 to occurrence risk of lung cancer and conducted a meta-analysis of the relationship between vitamin B6 and B12 intake and the risk of lung cancer. Fixed-effect meta-analysis was used to calculate pooled relative risks (RRs) and their 95% confidence intervals (CIs). We identified four observational studies (participants, n = 206,290; cases, n = 1,134) and three randomized controlled trials (RCTs; participants, n = 97,569; cases, n = 952). Vitamin B6 and B12 supplementary was not statistically significantly associated with occurrence risk of lung cancer (124/11926 (1.04%) vs. 73/8497 (0.86%), RR = 1.06, 95% CI = 0.78-1.43, P = 0.71). A consistent association was also observed, findings from RCTs did not support a protective effect of vitamin B6 and B12intake orally decrease the risk of lung cancer occurrence (HR = 1.13, 95% CI = 0.86-1.50, P = 0.39). For the women, there was no confirmed evidence demonstrated vitamin B intake can decrease the occurrence risk of lung cancer across the subgroup analyses (HR = 0.96, 95% CI = 0.80-1.16, P = 0.99). Dietary vitamin B6 and B12 intake also had no influence on occurrence risk of lung cancer in difference doses and intake duration. In conclusion, no confirmed links were found between vitamin B6 and B12 intake and risk of lung cancer occurrence.



Key wordsVitamin B      Lung cancer      Incidence      Vitamin B6      Vitamin B12     
Received: 06 March 2019      Published: 17 August 2019
Fund:  This work was sponsored by the Natural Science Foundation of China (81603590);National Traditional Chinese Medicine Clinical Research Base Long-Yi-Xue-Zhe (nurturing plan, LYTD-81).
Corresponding Authors: Cao Ya-Juan   
E-mail: dr_caoy@aliyun.com
Cite this article:

Li-Ping Shen, Rong Li, Ya-Juan Cao. Null links between vitamin B6 and B12 intake and occurrence risk of lung cancer: a meta-analysis. 93TMR Cancer, 2019, 2(4): 252-260. doi: 10.12032/TMRC201800054

URL:

https://www.tmrjournals.com/cancer/EN/10.12032/TMRC201800054     OR     https://www.tmrjournals.com/cancer/EN/Y2019/V2/I4/252

Figure 1 Study selection process
Studies Study design Country/Area Total cases (n) Lung Cancer cases (n) RR (95% CI) Controlled Variables Follow-up NOS scores
Oral
Ebbing 2009 [10] RCTs Norway 6845 92 Vitamin B6; 1.06 (0.62 - 1.82) and vitamin B9; 1.59 (0.92-2.75) - 78 (61 - 90) months -
Hankey 2012 [11] RCTs 104 medical centers in 20 countries on five continents 8164 29 Vitamin B; 0.91 (0.43 - 1.93) - Median 3.4 years -
Zhang 2008 [12] RCTs US 5442 23 Vitamin B; 1.04 (0.58 - 1.87) - Average 7.3 years -
Brasky 2017 [13] Cohort, prospective Western Washington 77,118 808 Vitamin B6; 1.82(1.25- 2.65) and Vitamin B12; 1.98(1.32- 2.97) Age, race, education, BMI, smoking status, alcohol consumption in the past year, history of chronic obstructive pulmonary disease, a personal history of cancer other than lung cancer, number of first-degree relatives with a history of lung cancer, and use of nonsteroidal anti-inflammatory drugs Median 6 years 8
Dietary
Bassett 2012 [14] Cohort, prospective Australia 41,514 348 - Smoking status Average 15 years 8
Kabat 2008 [15] Cohort, prospective Canadian 89,835 358 - Total energy intake Average 16.4 years 8
Takata 2012 [16] Cohort, prospective China 74,941 428 - Age, intakes of fruits, vegetables, and nutrients Median 11.2 years 8
Table 1 Baseline characteristics of included studies
Figure 2 Risk of bias graph and risk of bias summary
A, the risk of bias graph; B, the risk of bias summary.
Figure 3 Vitamin B for lung cancer incidence
Figure 4 The lung cancer incidence affected by vitamin B intake orally
Figure 5 Subgroup analysis of relationship between vitamin B6 intake and occurrence risk of lung cancer
Figure 6 Vitamin B6 and/or B12 intake and occurrence risk of lung cancer in female
Figure 7 Lung cancer incidences between vitamin B6 and/or B12 group and control group in female
Study Dietary Vitamin B intake Cases HR (95% CI) P value
Bassett 2012 [14] Vitamin B6 0.67
< 20th 92 1.0
20th- < 40th 68 0.96 (0.69 - 1.33)
40th- < 60th 58 0.87 (0.61 - 1.23)
60th- < 80th 59 0.94 (0.66 - 1.34)
> 80th 71 1.03 (0.74 - 1.43)
Vitamin B12 0.52
< 20th 62 1.0
20th- < 40th 66 1.03 (0.73 - 1.46)
40th- < 60th 71 1.03 (0.73 - 1.45)
60th- < 80th 70 1.04 (0.73 - 1.47)
> 80th 79 1.12 (0.79 - 1.59)
Folate 0.60
< 20th 87 1.0
20th- < 40th 63 0.90 (0.64 - 1.25)
40th- < 60th 68 1.13 (0.81 - 1.59)
60th- < 80th 69 1.16 (0.82 - 1.65)
> 80th 61 1.02 (0.69 - 1.50)
Kabat 2008 [15] Folate (μg/day) 0.79
< 237 - 1.0
237 to < 281 - 0.99 (0.87 - 1.13)
281 to < 321 - 1.03 (0.91 - 1.17)
321 to < 374 - 0.98 (0.86 - 1.12)
> 374 - 1.02 (0.90 - 1.17)
Takata 2012 [16] Vitamin B6 (mg/day, median) 0.44
1.12 126 1.0
1.47 113 1.14 (0.87 - 1.49)
1.79 88 0.97 (0.71 - 1.33)
2.32 101 1.21 (0.84 - 1.74)
Folate (μg/day, median) 0.79
185 129 1.0
248 85 0.76 (0.57 - 1.01)
308 111 1.02 (0.77 - 1.34)
405 103 0.96 (0.70 - 1.32)
Vitamin B12 (μg/day, median) 0.19
1.03 152 1.0
1.91 97 0.80 (0.61 - 1.04)
2.75 104 0.95 (0.72 - 1.25)
4.27 75 0.76 (0.55 - 1.05)
Table 2 Dietary vitamin B intake and occurrence risk of lung cancer
1.   Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018. CA Cancer J Clin 2018: 1-31.
doi: 10.3322/caac.21255 pmid: 25533606
2.   Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008. Int J Cancer 2010, 127: 2893-2917.
doi: 10.1002/ijc.25516 pmid: 21351269
3.   Fedde KN, Whyte MP. Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-50-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. Am J Hum Genet 1990, 47: 767-775.
pmid: 2220817
4.   Roth-Maier DA, Kettler SI, Kirchgessner M. Availability of vitamin B6 from different food sources. Int J Food Sci Nutr 2002, 53: 171-179.
doi: 10.1080/09637480220132184 pmid: 11939111
5.   Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008, 87: 517-533.
doi: 10.1093/ajcn/87.3.517 pmid: 18326588
6.   Kim YI. Folate and DNA methylation: A mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev 2004, 13: 511-519.
pmid: 15066913
7.   Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. .
8.   Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration. .
doi: 10.1002/14651858.CD008754.pub2 pmid: 22419337
9.   Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002, 21:1539-1558.
doi: 10.1002/sim.1186 pmid: 12111919
10.   Ebbing M, B?naa KH, Nyg?rd O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009, 302: 2119-2126.
doi: 10.1001/jama.2009.1622 pmid: 19920236
11.   Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: results of a randomized placebo-controlled trial. Stroke 2012, 43: 1572-1577.
doi: 10.1161/STROKEAHA.111.641613 pmid: 22474057
12.   Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA 2008, 300: 2012-2021.
doi: 10.1001/jama.2008.555 pmid: 18984888
13.   Brasky TM, White E, Chen CL. Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. J Clin Oncol 2017, 35: 3440-3448.
doi: 10.1200/JCO.2017.72.7735 pmid: 28829668
14.   Bassett JK, Hodge AM, English DR, et al. Dietary intake of B vitamins and methionine and risk of lung cancer. Eur J Clin Nutr 2012, 66: 182-187.
doi: 10.1038/ejcn.2011.157
15.   Kabat GC, Miller AB, Jain M, et al. Dietary intake of selected B vitamins in relation to risk of major cancers in women. Br J Cancer 2008, 99: 816-821.
doi: 10.1038/sj.bjc.6604540 pmid: 18665162
16.   Takata Y, Cai Q, Beeghly-Fadiel A, et al. Dietary B vitamin and methionine intakes and lung cancer risk occurrence risk of lung cancer among female never smokers in China. Cancer Causes Control 2012, 23: 1965-1975.
doi: 10.1007/s10552-012-0074-z pmid: 23065072
17.   García-Closas R, García-Closas M, Kogevinas M, et al. Food, nutrient and heterocyclic amine intake and the risk of bladder cancer. Eur J Cancer 2007, 43: 1731-1740.
doi: 10.1016/j.ejca.2007.05.007
18.   Mayne ST, Risch HA, Dubrow R, et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 2001, 10: 1055-1062.
pmid: 11588131
19.   Kaaks R, Tuyns AJ, Haelterman M, et al. Nutrient intake patterns and gastric cancer risk: a case-control study in Belgium. Int J Cancer 1998, 78: 415-420.
doi: 10.1002/(sici)1097-0215(19981109)78:4&amp;lt;415::aid-ijc4&amp;gt;3.0.co;2-x pmid: 9797127
20.   Negri E, Franceschi S, Bosetti C, et al. Selected micronutrients and oral and pharyngeal cancer. Int J Cancer 2000, 86: 122-127.
doi: 10.1002/(sici)1097-0215(20000401)86:1&amp;lt;122::aid-ijc19&amp;gt;3.0.co;2-2 pmid: 10728605
21.   Galeone C, Pelucchi C, Levi F, et al. Folate intake and squamous-cell carcinoma of the oesophagus in Italian and Swiss men. Ann Oncol 2006, 17: 521-525.
doi: 10.1093/annonc/mdj107 pmid: 16344275
22.   Schernhammer E, Wolpin B, Rifai N et al. Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res 2007, 67: 5553-5360.
doi: 10.1158/0008-5472.CAN-06-4463 pmid: 17545639
23.   Gong Z, Holly EA, Bracci PM. Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control 2009, 20: 1317-1325.
doi: 10.1007/s10552-009-9352-9 pmid: 19415507
24.   Zhang SM, Willett WC, Selhub J, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 2003, 95: 373-380.
doi: 10.1093/jnci/95.5.373 pmid: 12618502
25.   Lajous M, Lazcano-Ponce E, Hernandez-Avila M, et al. Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomarkers Prev 2006, 15: 443-438.
doi: 10.1158/1055-9965.EPI-05-0532 pmid: 16537699
26.   Zhang CX, Ho SC, Chen YM, et al. Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status. Br J Nutr 2011, 106: 936-943.
doi: 10.1017/S0007114511001140 pmid: 21736840
27.   Lim U, Schenk M, Kelemen LE, et al. Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000. Am J Epidemiol 2005, 162: 953-964.
doi: 10.1093/aje/kwi310 pmid: 16221809
28.   Lim U, Weinstein S, Albanes D, et al. Dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma and multiple myeloma in a cohort of male smokers. Cancer Epidemiol Biomarkers Prev 2006, 15: 1109-1114.
doi: 10.1158/1055-9965.EPI-05-0918 pmid: 16775167
29.   Kotsopoulos J, Hecht JL, Marotti JD, et al. Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumors. Int J Cancer 2010, 126: 2191-2198.
doi: 10.1002/ijc.24723 pmid: 19585555
30.   Harris HR, Cramer DW, Vitonis AF, et al. Folate, vitamin B6, vitamin B12 , methionine and alcohol intake in relation to ovarian cancer risk. Int J Cancer 2012, 131: E518-E529.
doi: 10.1002/ijc.26455 pmid: 21953625
31.   Key TJ, Silcocks PB, Davey GK, et al. A case-control study of diet and prostate cancer. Br J Cancer 1997, 76: 678-687.
doi: 10.1038/bjc.1997.445 pmid: 9303371
32.   Weinstein SJ, Hartman TJ, Stolzenberg-Solomon R, et al. Null association between prostate cancer and serum folate, vitamin B6, vitamin B12, and homocysteine. Cancer Epidemiol Biomarkers Prev 2012, 12: 1271-1272.
pmid: 14652294
33.   Harnack L, Jacobs DR Jr, Nicodemus K, et al. Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutr Cancer 2002, 43:152-158.
doi: 10.1207/S15327914NC432_5 pmid: 12588695
34.   Zhang SM, Moore SC, Lin J, et al. Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women. Am J Epidemiol 2006, 163: 108-115.
doi: 10.1093/aje/kwj016 pmid: 16339055
35.   Sharp L, Little J, Brockton NT, et al. 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 2008, 99: 379-389.
doi: 10.1017/S0007114507801073 pmid: 18053312
36.   Zhang SL, Chen TS, Ma CY, et al. Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality: A PRISMA-compliant cumulative meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016, 95: e3485.
doi: 10.1097/MD.0000000000003485 pmid: 27495015
37.   Clarke R, Halsey J, Lewington S, et al. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med 2010, 170: 1622-1631.
doi: 10.1001/archinternmed.2010.348 pmid: 20937919
38.   Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 2013, 381: 1029-1036.
doi: 10.1016/S0140-6736(12)62001-7
39.   Qin X, Cui Y, Shen L, et al. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer 2013, 133: 1033-1041.
doi: 10.1002/ijc.28038 pmid: 23338728
40.   Jia K, Wang R1, Tian J. Vitamin B6 Intake and the Risk of Colorectal Cancer: A Meta-Analysis of Prospective Cohort Studies. Nutr Cancer 2017, 69: 723-731.
doi: 10.1080/01635581.2017.1324633 pmid: 28569561
41.   Sun NH, Huang XZ, Wang SB, et al. A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk. Public Health Nutr 2016, 19: 1446-1456.
doi: 10.1017/S136898001500261X pmid: 26373257
42.   Wu W, Kang S, Zhang D. Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis. Br J Cancer 2013, 109: 1926-1944.
doi: 10.1038/bjc.2013.438 pmid: 23907430
43.   Collin SM, Metcalfe C, Refsum H, et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2010, 19: 1632-1642.
doi: 10.1158/1055-9965.EPI-10-0180 pmid: 20501771
44.   Mocellin S, Briarava M, Pilati P. Vitamin B6 and Cancer Risk: A Field Synopsis and Meta-Analysis. J Natl Cancer Inst 2017, 109: 1-9.
doi: 10.1093/jnci/djw235 pmid: 28423409
[1] Fan-Ming Kong, Yang Yao, Ren-Fen Deng, Tian-Qi Chen, Dong-Ying Liao, Xiao-Jiang Li, Ying-Jie Jia. Xiaoyan decoction inhibits tumor growth and improves the immunity of mouse with A549 lung carcinoma xenograft[J]. 93TMR Cancer, 2019, 2(4): 227-232.
[2] Ying-Ying Liu , Feng Xu . The clinical efficacy analysis of radiofrequency ablation combined with chemotherapy in treating late non-small cell lung cancer[J]. 93TMR Cancer, 2019, 2(3): 216-221.
[3] Liu Pu, Wei-Hao Chen, Kun-Ji Wu, Ji-Huan Lin, Cheng-Lu Li, Shu-Lian Chen, Lu-Xi Cao, Shi-Qi Wang, Shu-Jun Lin, Yi-Min Zhang, Ming-Min Zhu. Immunoregulation of KangAi injection combined with chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis[J]. 93TMR Cancer, 2019, 2(2): 170-180.
[4] Yan-Juan Zhu, Zou Ying, Hui-Hui Chen, Xiao-Feng Jiang, Xian Chen, Li-Rong Liu, Yi-Hong Liu, Hai-Bo Zhang. Effect of Chinese medicine prescriptions of warming-Yang or cooling-heat combined with Gefitinib on H1650 cell line[J]. 93TMR Cancer, 2018, 1(1): 22-28.