Individual Genetics, Coffee Consumption, BRCA1 and Breast Cancer

Reading time: 6 – 10 minutes

We’ve talked previously about the health benefits of coffee and the antioxidant compounds responsible for it’s bitterness. To add to the “perks” of coffee consumption, a recent report in the Journal of Cancer Epidemiology Biomarkers & Prevention suggests that caffeine protects against breast cancer in women that have a BRCA1 gene mutation [1].

What is BRCA1? The acronym stands for breast cancer 1, early onset. The BRCA1 gene encodes a protein that plays a role in maintaining genomic stability and acts as a tumor suppressor. Approximately 5%-10% of breast cancer and ovarian cancer is hereditary and 30%-50% of these are due to DNA mutations in the genes BRCA1 and BRCA2 [2]. Women age 35-40 that carry the BRCA1 mutation are particularly susceptible with a risk between 45%-60% of developing breast cancer [2]. The absolute risk of cancer by age 70 is reported to be between 45% and 87% [3-4].

The authors of the report had previously evaluated the association between coffee consumption and the risk of breast cancer among women who had detrimental mutations in either BRCA1 or BRCA2. They observed a statistically significant reduction in the risk of breast cancer among women who consumed six or more cups of coffee per day compared to those who never drank coffee [5]. The association was only observed for BRCA1 and for caffeinated coffee.

Ninety-five percent of caffeine is metabolized in the human body by a member of the cytochrome P450 family of enzymes, CYP1A2, which stands for cytochrome P450, family 1, subfamily A, polypeptide 2. The cytochrome P450 proteins catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. CYP1A2 also metabolizes acetaminophen (Tylenol) and caffeine. Decreased enzyme activation and impaired caffeine metabolism is associated with a common A to C polymorphism in the CYP1A2 gene (meaning a genetic variation in an individual’s DNA sequence, in this case a specific A to C basepair substitution that alters the function of CYP1A2) [6].

In the present study, the authors examined whether the CYP1A2 genotype (meaning a person’s genetic makeup, in this case the difference in the CYP1A2 DNA sequence between individuals) modifies the association between a history of coffee consumption and the risk of breast cancer. A total of 411 BRCA1 mutation carriers (170 cases and 241 controls) and their coffee consumption habits were evaluated. The CYP1A2 genotype did not affect breast cancer risk. However, among women with at least one variant C allele (meaning an alternative DNA coding sequence) in CYP1A2, specifically the CYP1A2*1F allele (an A to C basebair substitution at a specific location in one or both copies of the DNA coding sequence for CYP1A2), those who drank coffee had nearly a 3-fold decrease in the risk of breast cancer compared with women who never drank coffee.

The authors suggest that mechanisms other than induction of CYP1A2 may account for the influence of caffeine on breast cancer risk. Coffee contains a number of biochemically active compounds including caffeine, phytoestrogens (including flavonoids) and other phytonutrients (including tocopherols). However, caffeine is the only major compound in coffee known to be metabolized by CYP1A2. Thus the authors attribute the decrease in breast cancer risk to prolonged caffeine exposure among individuals that are “slow metabolizers”.

Coffee is a major contributor to the total in vitro antioxidant capacity of the diet. An investigation of the quality of vitamin and polyphenolic antioxidants in beverages found that black tea contained the highest concentration of high-quality antioxidants, followed by coffee [7]. Here’s the breakdown:

This may be particularly relevant for women who carry the BRCA1 mutation as a decrease in the expression of genes involved in the antioxidant response has been shown for BRCA1-deficient cells [8].

A separate hospital-based, case-control study done last year evaluating the role of coffee in breast cancer etiology found among premenopausal women that consumption of caffeinated coffee was associated with a decrease in breast cancer risk [9]. The study included 1,932 women with primary, incident breast cancer and 1,895 controls. Women who consumed four or more cups of coffee per day experienced a 40% reduction in breast cancer risk. Although this study didn’t examine individual genetics, it is one of many demonstrating coffee’s protective effects against breast cancer.

It’s fascinating that impairment of caffeine metabolism coupled with high coffee consumption can result in a reduction in breast cancer risk for women who have an otherwise increased risk due to a BRCA1 gene mutation. The BRCA1 variant C allele isn’t common; in their previous study, the authors indicate that >95% of the mutations identified weren’t pathogenic [5]. Nevertheless, these results underscore the importance of addressing individual genetic variability in the metabolism when evaluating diet-disease associations.

References

1. Kotsopoulos et al. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):912-6. DOI: 10.1158/1055-9965.EPI-06-1074
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2. Ferla et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007 Jun;18 Suppl 6:vi93-8.
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3. Antoniou et al. Risk models for familial ovarian and breast cancer. Genet Epidemiol. 2000 Feb;18(2):173-90.
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4. Ford et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 Mar 19;343(8899):692-5.
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5. Nkondjock et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2006 Jan 1;118(1):103-7.
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6. Sachse et al. Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999 Apr;47(4):445-9.
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7. Vinson et al. Vitamins and especially flavonoids in common beverages are powerful in vitro antioxidants which enrich lower density lipoproteins and increase their oxidative resistance after ex vivo spiking in human plasma. J Agric Food Chem. 1999 Jul;47(7):2502-4.
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8. Bae et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004 Nov 1;64(21):7893-909.
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9. Baker et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer. 2005;52(1):15-21.
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