Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 4/2015

01-04-2015 | Original Article - Cancer Research

The plasma level of retinol, vitamins A, C and α-tocopherol could reduce breast cancer risk? A meta-analysis and meta-regression

Authors: Fulan Hu, Zhiwei Wu, Guangxiao Li, Chong Teng, Yupeng Liu, Fan Wang, Yashuang Zhao, Da Pang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2015

Login to get access

Abstract

Purpose

Plasma antioxidants are supposed to be directly related to breast cancer risk. However, the results remain inconsistent. Herein, we carried this meta-analysis to comprehensively summarize the associations between plasma retinol, vitamins A, C and α-tocopherol and breast cancer risk.

Methods

We searched PubMed, Embase and the Cochrane Databases (through September 24, 2014) and the reference lists of the retrieved articles in English with sufficient information to estimate relative risk or odds ratio and the 95 % confidence intervals (CIs), or with mean serum/plasma level of vitamins and SD/SEM/p value in breast cancer and controls. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.

Results

Forty studies entered this meta-analysis. For the pooled OR, no significant association between plasma retinol and breast cancer was observed (p = 0.13). Significant association was observed between plasma α-tocopherol and breast cancer (pooled OR 0.42, 95 % CI 0.25, 0.72, p = 0.00) in the subgroup with the median lowest level of 5.74–9.16 μmol/L. For the weighted mean difference (WMD), the plasma α-tocopherol and vitamin C level between breast cancer and controls were significantly different [WMD = −0.93 μmol/L (95 % CI −1.26, −0.61, p = 0.00) and −2.51 μmol/L (95 % CI −4.00, −1.02, p = 0.00), respectively]. No significant association between plasma retinol and vitamin A and breast cancer was observed.

Conclusions

Severe α-tocopherol deficiency could increase breast cancer risk. The association between plasma vitamin C and breast cancer was only significant in case–control studies. There was no significant association between other vitamins and breast cancer risk.
Appendix
Available only for authorised users
Literature
go back to reference Abiaka C, Al-Awadi F, Gulshan S, Al-Sayer H, Behbehani A, Farghaly M, Simbeye A (2001) Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer. J Clin Pharm Ther 26:265–270CrossRefPubMed Abiaka C, Al-Awadi F, Gulshan S, Al-Sayer H, Behbehani A, Farghaly M, Simbeye A (2001) Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer. J Clin Pharm Ther 26:265–270CrossRefPubMed
go back to reference Aghvami T, Djalali M, Keshavarz A, Sadeghi MR, Zeraati H, Sadrzadeh Yeganeh H, Negahdar M (2006) Plasma level of antioxidant vitamins and lipid peroxidation in breast cancer patients. Iran J Public Health 35:42–47 Aghvami T, Djalali M, Keshavarz A, Sadeghi MR, Zeraati H, Sadrzadeh Yeganeh H, Negahdar M (2006) Plasma level of antioxidant vitamins and lipid peroxidation in breast cancer patients. Iran J Public Health 35:42–47
go back to reference Al-Saleh I, Al-Doush I (2002) Serum selenium and dl-(alpha)-tocopherol levels in women with breast cancer. Trace Elem Electrolytes 19:118–124 Al-Saleh I, Al-Doush I (2002) Serum selenium and dl-(alpha)-tocopherol levels in women with breast cancer. Trace Elem Electrolytes 19:118–124
go back to reference Armstrong B, Doll R (1975) Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 15:617–631CrossRefPubMed Armstrong B, Doll R (1975) Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 15:617–631CrossRefPubMed
go back to reference Ascherio A, Stampfer MJ, Colditz GA, Rimm EB, Litin L, Willett WC (1992) Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J Nutr 122:1792–1801PubMed Ascherio A, Stampfer MJ, Colditz GA, Rimm EB, Litin L, Willett WC (1992) Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J Nutr 122:1792–1801PubMed
go back to reference Basu TK, Hill GB, Ng D, Abdi E, Temple N (1989) Serum vitamins A and E, beta-carotene, and selenium in patients with breast cancer. J Am Coll Nutr 8:524–529CrossRefPubMed Basu TK, Hill GB, Ng D, Abdi E, Temple N (1989) Serum vitamins A and E, beta-carotene, and selenium in patients with breast cancer. J Am Coll Nutr 8:524–529CrossRefPubMed
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed
go back to reference Berlin JA, Longnecker MP, Greenland S (1993) Meta-analysis of epidemiologic dose–response data. Epidemiology 4:218–228CrossRefPubMed Berlin JA, Longnecker MP, Greenland S (1993) Meta-analysis of epidemiologic dose–response data. Epidemiology 4:218–228CrossRefPubMed
go back to reference Buell P (1973) Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51:1479–1483PubMed Buell P (1973) Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51:1479–1483PubMed
go back to reference Chene G, Thompson SG (1996) Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form. Am J Epidemiol 144:610–621CrossRefPubMed Chene G, Thompson SG (1996) Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form. Am J Epidemiol 144:610–621CrossRefPubMed
go back to reference Ching S, Ingram D, Hahnel R, Beilby J, Rossi E (2002) Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 132:303–306PubMed Ching S, Ingram D, Hahnel R, Beilby J, Rossi E (2002) Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 132:303–306PubMed
go back to reference Chitkara N, Dadoo RC, Bansal S, Chugh K, Aggarwal SK, Lal H (1996) Plasma vitamin E levels in carcinoma breast. Indian J Clin Biochem 11:162–164CrossRef Chitkara N, Dadoo RC, Bansal S, Chugh K, Aggarwal SK, Lal H (1996) Plasma vitamin E levels in carcinoma breast. Indian J Clin Biochem 11:162–164CrossRef
go back to reference de Cavanagh EM, Honegger AE, Hofer E, Bordenave RH, Bullorsky EO, Chasseing NA, Fraga C (2002) Higher oxidation and lower antioxidant levels in peripheral blood plasma and bone marrow plasma from advanced cancer patients. Cancer 94:3247–3251. doi:10.1002/cncr.10611 CrossRefPubMed de Cavanagh EM, Honegger AE, Hofer E, Bordenave RH, Bullorsky EO, Chasseing NA, Fraga C (2002) Higher oxidation and lower antioxidant levels in peripheral blood plasma and bone marrow plasma from advanced cancer patients. Cancer 94:3247–3251. doi:10.​1002/​cncr.​10611 CrossRefPubMed
go back to reference Deharveng G, Charrondiere UR, Slimani N, Southgate DA, Riboli E (1999) Comparison of nutrients in the food composition tables available in the nine European countries participating in EPIC. European Prospective Investigation into Cancer and Nutrition. Eur J Clin Nutr 53:60–79CrossRefPubMed Deharveng G, Charrondiere UR, Slimani N, Southgate DA, Riboli E (1999) Comparison of nutrients in the food composition tables available in the nine European countries participating in EPIC. European Prospective Investigation into Cancer and Nutrition. Eur J Clin Nutr 53:60–79CrossRefPubMed
go back to reference Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, Stephenson HE Jr (1998) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9:89–97CrossRefPubMed Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, Stephenson HE Jr (1998) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9:89–97CrossRefPubMed
go back to reference Gerber M et al (1988) Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France. Int J Cancer 42:489–494CrossRefPubMed Gerber M et al (1988) Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France. Int J Cancer 42:489–494CrossRefPubMed
go back to reference Gerber M, Richardson S, de Paulet PC, Pujol H, de Paulet AC (1989) Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects. Cancer 64:2347–2353CrossRefPubMed Gerber M, Richardson S, de Paulet PC, Pujol H, de Paulet AC (1989) Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects. Cancer 64:2347–2353CrossRefPubMed
go back to reference Gerber M, Richardson S, Salkeld R, Chappuis P (1991) Antioxidants in female breast cancer patients. Cancer Invest 9:421–428CrossRefPubMed Gerber M, Richardson S, Salkeld R, Chappuis P (1991) Antioxidants in female breast cancer patients. Cancer Invest 9:421–428CrossRefPubMed
go back to reference Hou MF et al (1998) Serum vitamin A level in breast cancer patients Kaohsiung. J Med Sci 14:673–678 Hou MF et al (1998) Serum vitamin A level in breast cancer patients Kaohsiung. J Med Sci 14:673–678
go back to reference Hulten K, Van Kappel AL, Winkvist A, Kaaks R, Hallmans G, Lenner P, Riboli E (2001) Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 12:529–537CrossRefPubMed Hulten K, Van Kappel AL, Winkvist A, Kaaks R, Hallmans G, Lenner P, Riboli E (2001) Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 12:529–537CrossRefPubMed
go back to reference Ito Y, Gajalakshmi KC, Sasaki R, Suzuki K, Shanta V (1999) A study on serum carotenoid levels in breast cancer patients of Indian women in Chennai (Madras), India. J Epidemiol 9:306–314CrossRefPubMed Ito Y, Gajalakshmi KC, Sasaki R, Suzuki K, Shanta V (1999) A study on serum carotenoid levels in breast cancer patients of Indian women in Chennai (Madras), India. J Epidemiol 9:306–314CrossRefPubMed
go back to reference Kelsey JL, Horn-Ross PL (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15:7–16PubMed Kelsey JL, Horn-Ross PL (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15:7–16PubMed
go back to reference Kim MK, Ahn SH, Lee-Kim YC (2001) Relationship of serum (alpha)-tocopherol, carotenoids and retinol with the risk of breast cancer. Nutr Res 21:797–809CrossRef Kim MK, Ahn SH, Lee-Kim YC (2001) Relationship of serum (alpha)-tocopherol, carotenoids and retinol with the risk of breast cancer. Nutr Res 21:797–809CrossRef
go back to reference Knekt P et al (1990) Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. Am J Epidemiol 132:857–870PubMed Knekt P et al (1990) Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. Am J Epidemiol 132:857–870PubMed
go back to reference London SJ et al (1992) Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer. Cancer Causes Control 3:503–512CrossRefPubMed London SJ et al (1992) Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer. Cancer Causes Control 3:503–512CrossRefPubMed
go back to reference Maillard V et al (2009) Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N-EPIC study. Int J Cancer 127:1188–1196. doi:10.1002/ijc.25138 CrossRef Maillard V et al (2009) Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N-EPIC study. Int J Cancer 127:1188–1196. doi:10.​1002/​ijc.​25138 CrossRef
go back to reference Marubini E et al (1988) The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case–control study. Cancer 61:173–180CrossRefPubMed Marubini E et al (1988) The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case–control study. Cancer 61:173–180CrossRefPubMed
go back to reference McPherson RAPM (2011) Henry’s clinical diagnosis and management by laboratory methods, 22nd edn. Elsevier Saunders, Philadelphia McPherson RAPM (2011) Henry’s clinical diagnosis and management by laboratory methods, 22nd edn. Elsevier Saunders, Philadelphia
go back to reference Potischman N et al (1990) Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. Am J Clin Nutr 52:909–915PubMed Potischman N et al (1990) Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. Am J Clin Nutr 52:909–915PubMed
go back to reference Ray G, Husain SA (2001) Role of lipids, lipoproteins and vitamins in women with breast cancer. Clin Biochem 34:71–76CrossRefPubMed Ray G, Husain SA (2001) Role of lipids, lipoproteins and vitamins in women with breast cancer. Clin Biochem 34:71–76CrossRefPubMed
go back to reference Russell MJ, Thomas BS, Bulbrook RD (1988) A prospective study of the relationship between serum vitamins A and E and risk of breast cancer. Br J Cancer 57:213–215CrossRefPubMedCentralPubMed Russell MJ, Thomas BS, Bulbrook RD (1988) A prospective study of the relationship between serum vitamins A and E and risk of breast cancer. Br J Cancer 57:213–215CrossRefPubMedCentralPubMed
go back to reference Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 11:451–457PubMed Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 11:451–457PubMed
go back to reference Schrijver J, Alexieva-Figusch J, Van Breederode N, Van Gilse HA (1987) Investigations on the nutritional status of advanced breast cancer patients. The influence of long-term treatment with megestrol acetate or tamoxifen. Nutr Cancer 10:231–245CrossRefPubMed Schrijver J, Alexieva-Figusch J, Van Breederode N, Van Gilse HA (1987) Investigations on the nutritional status of advanced breast cancer patients. The influence of long-term treatment with megestrol acetate or tamoxifen. Nutr Cancer 10:231–245CrossRefPubMed
go back to reference Shah FD, Patel JB, Shukla SN, Shah PM, Patel PS (2009) Evaluation of plasma non-enzymatic antioxidants in breast cancer etiology. Asian Pac J Cancer Prev 10:91–96PubMed Shah FD, Patel JB, Shukla SN, Shah PM, Patel PS (2009) Evaluation of plasma non-enzymatic antioxidants in breast cancer etiology. Asian Pac J Cancer Prev 10:91–96PubMed
go back to reference Sharhar S et al (2008) Antioxidant intake and status, and oxidative stress in relation to breast cancer risk: a case–control study. Asian Pac J Cancer Prev 9:343–349PubMed Sharhar S et al (2008) Antioxidant intake and status, and oxidative stress in relation to breast cancer risk: a case–control study. Asian Pac J Cancer Prev 9:343–349PubMed
go back to reference Simon MS, Djuric Z, Dunn B, Stephens D, Lababidi S, Heilbrun LK (2000) An evaluation of plasma antioxidant levels and the risk of breast cancer: a pilot case control study. Breast J 6:388–395CrossRefPubMed Simon MS, Djuric Z, Dunn B, Stephens D, Lababidi S, Heilbrun LK (2000) An evaluation of plasma antioxidant levels and the risk of breast cancer: a pilot case control study. Breast J 6:388–395CrossRefPubMed
go back to reference Stroup DF et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMed Stroup DF et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMed
go back to reference Thomas DB, Karagas MR (1987) Cancer in first and second generation Americans. Cancer Res 47:5771–5776PubMed Thomas DB, Karagas MR (1987) Cancer in first and second generation Americans. Cancer Res 47:5771–5776PubMed
go back to reference Toniolo P, Van Kappel AL, Akhmedkhanov A, Ferrari P, Kato I, Shore RE, Riboli E (2001) Serum carotenoids and breast cancer. Am J Epidemiol 153:1142–1147CrossRefPubMed Toniolo P, Van Kappel AL, Akhmedkhanov A, Ferrari P, Kato I, Shore RE, Riboli E (2001) Serum carotenoids and breast cancer. Am J Epidemiol 153:1142–1147CrossRefPubMed
go back to reference Torun M, Akgul S, Sargin H (1995a) Serum vitamin E level in patients with breast cancer. J Clin Pharm Ther 20:173–178CrossRefPubMed Torun M, Akgul S, Sargin H (1995a) Serum vitamin E level in patients with breast cancer. J Clin Pharm Ther 20:173–178CrossRefPubMed
go back to reference Torun M, Yardim S, Gonenc A, Sargin H, Menevse A, Simsek B (1995b) Serum beta-carotene, vitamin E, vitamin C and malondialdehyde levels in several types of cancer. J Clin Pharm Ther 20:259–263CrossRefPubMed Torun M, Yardim S, Gonenc A, Sargin H, Menevse A, Simsek B (1995b) Serum beta-carotene, vitamin E, vitamin C and malondialdehyde levels in several types of cancer. J Clin Pharm Ther 20:259–263CrossRefPubMed
go back to reference Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98:459–471CrossRefPubMed Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98:459–471CrossRefPubMed
go back to reference Ullah MF, Khan HY, Zubair H, Shamim U, Hadi SM (2011) The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol 67:103–110. doi:10.1007/s00280-010-1290-4 CrossRefPubMed Ullah MF, Khan HY, Zubair H, Shamim U, Hadi SM (2011) The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol 67:103–110. doi:10.​1007/​s00280-010-1290-4 CrossRefPubMed
go back to reference WHO (2011(WHO/NMH/NHD/MNM/11.3)) Serum retinol concentrations for determining the prevalence of vitamin A deficiency in populations Vitamin and Mineral Nutrition Information System. World Health Organization, Geneva WHO (2011(WHO/NMH/NHD/MNM/11.3)) Serum retinol concentrations for determining the prevalence of vitamin A deficiency in populations Vitamin and Mineral Nutrition Information System. World Health Organization, Geneva
Metadata
Title
The plasma level of retinol, vitamins A, C and α-tocopherol could reduce breast cancer risk? A meta-analysis and meta-regression
Authors
Fulan Hu
Zhiwei Wu
Guangxiao Li
Chong Teng
Yupeng Liu
Fan Wang
Yashuang Zhao
Da Pang
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 4/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1852-7

Other articles of this Issue 4/2015

Journal of Cancer Research and Clinical Oncology 4/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.