Taking folate in pregnancy and risk of maternal breast cancer
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《英国医生杂志》
1 Dugald Baird Centre For Research on Women's Health, Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, 2 Unit of Paediatric and Perinatal Epidemiology, Division of Child Health, Bristol BS8 1TQ, 3 Department of Social Medicine, University of Bristol, Bristol B58 2PR
Correspondence to: A R Ness Andy.Ness@bris.ac.uk
Introduction
In women randomised to high doses of supplemental folate, all cause mortality was about a fifth greater, and the risk of deaths attributable to breast cancer was twice as great. This increased risk in deaths attributable to breast cancer is unlikely to be due to competing causes as the number of deaths was small and all cause mortality appeared to be greater. The increase in mortality and in death from breast cancer with high doses of folate could be a chance finding. The number of deaths was small, the confidence intervals were wide, and we had no prespecified hypothesis that taking folate supplements in pregnancy would increase the risk of cancer. As this randomised trial was of high quality, bias and confounding are unlikely explanations for our findings. A recent study indicated that rats fed diets deficient in folate had increased mammary tumorigenesis compared with rats fed diets with sufficient folate,5 whereas rats fed a high dose folate diet had similar levels of tumorigenesis to deficient rats.5 Our data are preliminary and these findings require confirmation.
What this paper suggests
Women taking high doses of folate throughout pregnancy may be more likely to die from breast cancer in later life than women taking no folate
What research is needed now
This may be a chance finding, so further studies should examine the association between folate supplementation in pregnancy and risk of breast cancer
Contributors: DC did the fieldwork and the analysis. AN wrote the first draft. All the authors commented on this and subsequent drafts. AN is guarantor.
Funding: The original study had a project grant from the board of management for the Aberdeen Special Hospitals. Glaxo supplied the tablets. A project grant from the British Heart Foundation supported the reanalysis and follow up.
Competing interests: None declared.
Ethical approval: Multi-Centre Research Ethics Committee and the local Grampian Research Ethics Committee.
References
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 1991;338: 131-7.
Lucock M. Is folic acid the ultimate functional food component for disease prevention? BMJ 2004;328: 211-4.
Hall MH. Folic acid deficiency and congenital malformation. J Obstet Gynaecol Br Commonw 1972;79: 159-61.
Charles DHM, Ness AR, Campbell D, Davey Smith G, Whitley E, Hall MH. Folate and birth outcome: reanalysis of a large randomised controlled trial. Paediatr Perinat Epidemiol 2005; 19. (In press.)
Kotsopolous J, Kyoung-Jin S, Martin R, Choi M, Renlund R, McKerlie C, et al. Dietary folate deficiency suppresses N- methyl-N-nitrosourea-induced mammary tumorigenesis in rats. Carcinogenesis 2003;24: 937-44.(Deborah Charles, research)
Correspondence to: A R Ness Andy.Ness@bris.ac.uk
Introduction
In women randomised to high doses of supplemental folate, all cause mortality was about a fifth greater, and the risk of deaths attributable to breast cancer was twice as great. This increased risk in deaths attributable to breast cancer is unlikely to be due to competing causes as the number of deaths was small and all cause mortality appeared to be greater. The increase in mortality and in death from breast cancer with high doses of folate could be a chance finding. The number of deaths was small, the confidence intervals were wide, and we had no prespecified hypothesis that taking folate supplements in pregnancy would increase the risk of cancer. As this randomised trial was of high quality, bias and confounding are unlikely explanations for our findings. A recent study indicated that rats fed diets deficient in folate had increased mammary tumorigenesis compared with rats fed diets with sufficient folate,5 whereas rats fed a high dose folate diet had similar levels of tumorigenesis to deficient rats.5 Our data are preliminary and these findings require confirmation.
What this paper suggests
Women taking high doses of folate throughout pregnancy may be more likely to die from breast cancer in later life than women taking no folate
What research is needed now
This may be a chance finding, so further studies should examine the association between folate supplementation in pregnancy and risk of breast cancer
Contributors: DC did the fieldwork and the analysis. AN wrote the first draft. All the authors commented on this and subsequent drafts. AN is guarantor.
Funding: The original study had a project grant from the board of management for the Aberdeen Special Hospitals. Glaxo supplied the tablets. A project grant from the British Heart Foundation supported the reanalysis and follow up.
Competing interests: None declared.
Ethical approval: Multi-Centre Research Ethics Committee and the local Grampian Research Ethics Committee.
References
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 1991;338: 131-7.
Lucock M. Is folic acid the ultimate functional food component for disease prevention? BMJ 2004;328: 211-4.
Hall MH. Folic acid deficiency and congenital malformation. J Obstet Gynaecol Br Commonw 1972;79: 159-61.
Charles DHM, Ness AR, Campbell D, Davey Smith G, Whitley E, Hall MH. Folate and birth outcome: reanalysis of a large randomised controlled trial. Paediatr Perinat Epidemiol 2005; 19. (In press.)
Kotsopolous J, Kyoung-Jin S, Martin R, Choi M, Renlund R, McKerlie C, et al. Dietary folate deficiency suppresses N- methyl-N-nitrosourea-induced mammary tumorigenesis in rats. Carcinogenesis 2003;24: 937-44.(Deborah Charles, research)