March 24, 2014

Coffee Lowers Brain Tumor Risk

Study finds a change in the relative risk of glioma or meningioma with increased caffeine consumption.
These new data are consistent with a number of earlier publications that suggest both a strong protective effect and possibly a useful therapeutic effect from coffee or caffeine against glioma. Members of the public frequently view coffee in a negative light and will often "give it up" after a cancer diagnosis. At least in the case of glioma, coffee may have benefit, and these patients should be discouraged from discontinuing their coffee consumption.

Reference

Michaud DS, Gallo V, Schlehofer B, et al. Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am J Clin Nutr. 2010 Nov;92(5):1145-1150.

Design

Data on coffee and tea intake was analyzed using Cox proportional hazard models seeking a relationship with brain tumor risk.

Participants

Dietary data from 343 cases of glioma and 245 cases of meningioma from 9 countries were analyzed.
Study "Medication": Reported consumption of coffee or tea.

Primary Measures

Change in relative risk of glioma or meningioma with increased coffee and tea consumption.

Key Findings

A significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P=0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31); however, neither of these later 2 associations reached statistical significance.

Practice Implications

These new data are consistent with a number of earlier publications that suggest both a strong protective effect and possibly a useful therapeutic effect from coffee or caffeine against glioma. Members of the public frequently view coffee in a negative light and will often “give it up” after a cancer diagnosis. At least in the case of glioma, coffee may have benefit, and these patients should be discouraged from discontinuing their coffee consumption.

Holick et al already reported that coffee lowered risk of glioma in January 2010. In this earlier paper, data from 3 prospective cohort studies were combined to yield 335 incident cases of glioma. Consumption of 5 or more cups of coffee and tea per day compared with no consumption decreased risk significantly (RR, 0.60; 95% CI, 0.41–0.87; P(trend)=0.04). The inverse association was stronger in men (RR, 0.46; 95% CI, 0.26–0.81; P(trend) = 0.03).1

Other recent studies suggest coffee, in particular caffeine, may be more than protective against glioma and that both may have therapeutic value during treatment of glioma.

In February 2010, Kang et al reported that caffeine might be a useful adjunctive therapy against invasive glioma. After showing that caffeine inhibited migration of glioblastoma cells in various in vitro assays, the researchers showed in vivo that caffeine greatly increased mean survival using a mouse xenograft model of glioblastoma.2

Caffeine sensitizes glioma cells to both ionizing radiation and chemotherapy.

Caffeine sensitizes glioma cells to both ionizing radiation and chemotherapy. In February 2010, Sinn et al reported that “caffeine or its derivative pentoxifylline are promising candidate drugs for the radiosensitization of glioma cells.”3 Caffeine also enhances the effect of the chemotherapy drug temozolomide (Temador), which is often used in conjunction with radiation to treat malignant glioma.4

One possible explanation for these benefits is that coffee is a peroxisome proliferator-activated receptor (PPAR) gamma agonist.5 PPAR gamma agonists not only inhibit brain tumor growth,6 but they may also inhibit brain cancer stem cells.7

Interestingly, a number of synthetic PPAR gamma agonists are already under investigation for treating brain tumors. Ciglitazone and troglitazone, both synthetic PPAR gamma agonists, are being investigated and showing promise.8,9 Pioglitazone (Actos), a drug already used to treat diabetes, may be of possible use. A 2006 study using a rat glioma model reported that “oral administration of pioglitazone reduced tumor volumes by 76.9%. Subsequent brain tissue analysis revealed induction of apoptotic cell death.”10

Leaving all of these interesting details aside for the moment, our bottom line should be that glioma patients should be drinking coffee with the caffeine still in it. The next time a patient with a malignant glioma tells you they have stopped drinking coffee to be healthy, explain to them that it’s better to drink more coffee rather than less.

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References

1. Holick CN, Smith SG, Giovannucci E, Michaud DS. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol Biomarkers Prev. 2010;19(1):39-47.

2. Kang SS, Han KS, Ku BM, et al. Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer Res. 2010;70(3):1173-1183.

3. Sinn B, Tallen G, Schroeder G, et al. Caffeine confers radiosensitization of PTEN-deficient malignant glioma cells by enhancing ionizing radiation-induced G1 arrest and negatively regulating Akt phosphorylation. Mol Cancer Ther. 2010;9(2):480-488.

4. Chalmers AJ, Ruff EM, Martindale C, Lovegrove N, Short SC. Cytotoxic effects of temozolomide and radiation are additive- and schedule-dependent. Int J Radiat Oncol Biol Phys. 2009;75(5):1511-1519.

5. Choi SY, Chung JH, Kim DH, et al. Peroxisome proliferator-activated receptor gamma agonist action of 3-methyl-1,2-cyclopentanedione. Biochim Biophys Acta. 2007;1770(12):1612-1619.

6. Grommes C, Conway DS, Alshekhlee A, Barnholtz-Sloan JS. Inverse association of PPARgamma agonists use and high grade glioma development. J Neurooncol. 2010 May 5.

7. Chearwae W, Bright JJ. PPARgamma agonists inhibit growth and expansion of CD133+ brain tumour stem cells. Br J Cancer. 2008;99(12):2044-2053.

8. Kang DW, Choi CH, Park JY, Kang SK, Kim YK. Ciglitazone induces caspase-independent apoptosis through down-regulation of XIAP and survivin in human glioma cells. Neurochem Res. 2008;33(3):551-561.

9. Coras R, Hölsken A, Seufert S, et al. The peroxisome proliferator-activated receptor-gamma agonist troglitazone inhibits transforming growth factor-beta-mediated glioma cell migration and brain invasion. Mol Cancer Ther. 2007;6(6):1745-1754.

10. Grommes C, Landreth GE, Sastre M, et al. Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. Mol Pharmacol. 2006;70(5):1524-1533.