Carcinogenesis Advance Access originally published online on July 31, 2008
Carcinogenesis 2008 29(10):1967-1972; doi:10.1093/carcin/bgn177
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Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study
1 Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
2 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South Second Street, Minneapolis, MN 55454, USA
3 USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
4 Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117598, Singapore
* To whom correspondence should be addressed. Tel: +1 612 624 1818; Fax: +1 612 624 0315; Email: robie004{at}umn.edu
The tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) has been reported to act as a cancer preventive agent through folate pathway inhibition in experimental studies. We hypothesized that if folate pathway inhibition is the mechanism of cancer preventive activities of EGCG, then the protective effect against breast cancer would be stronger among women with low dietary folate intake and the high-activity methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genotypes. In a nested case–control study of 380 women with incident breast cancer and 662 controls within the Singapore Chinese Health Study, we found no association between either green tea intake or gene polymorphisms of MTHFR (C677T and A1298C) and TYMS (1494 ins/del) and breast cancer risk. However, among women with low folate intake (<133.4 µg/day), weekly/daily green tea intake was inversely associated with breast cancer risk compared with less green tea intake [odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26–0.79, P for interaction = 0.02]. Among women with high folate intake (
133.4 µg/day), green tea intake was not associated with breast cancer. Similarly, among women possessing the high-activity MTHFR/TYMS genotypes (0–1 variant allele), weekly/daily versus less frequent green tea intake was associated with lower breast cancer risk (OR = 0.66, 95% CI = 0.45–0.98), which was observed even more strongly among those who also had low folate intake (OR = 0.44, 95% CI = 0.22–0.89) than high folate intake (OR = 0.92, 95% CI = 0.55–1.54). This association was not observed among women possessing the low-activity genotypes (2–4 variant alleles). Our findings suggest that folate pathway inhibition may be one mechanism through which green tea protects against breast cancer in humans.
Abbreviations: CI, confidence interval; EGCG, (–)-epigallocatechin-3-gallate; MTHFR, methylenetetrahydrofolate reductase; OR, odds ratio; SCHS, Singapore Chinese Health Study; TYMS, thymidylate synthase
Received May 21, 2008; revised July 23, 2008; accepted July 27, 2008.