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Here’s another reason to enjoy your coffee. A recent study in the July edition of the Journal Hepatology found a significant inverse association (meaning opposingly related; an increase in one variable results in a decrease in another) between coffee drinking and the risk of primary liver cancer [1]. The study also found that serum levels of an antioxidant enzyme, elevated in people with low coffee consumption, were associated with an increased risk of developing the disease.

photo credit: Marcelo Alves

Primary liver and bile duct cancers are the sixth most common cause of cancer death in men and the tenth most common cause of cancer death in women [2]. Hepatitis B and C viral infections have been identified as causative factors in greater than 75% of liver cancers worldwide [3]. Interestingly, incidence rates are low in most developed countries except for Japan, where coffee drinking is relatively uncommon. Several studies have also identified an inverse association between coffee consumption and serum levels of gamma-glutamyltransferase (GGT), an enzyme involved in glutathione metabolism [4-5]. Glutathione plays important roles in antioxidant defense, nutrient defense and regulation of a variety of cellular events [6].

Residents of Finland consume more coffee per capita than the Japanese, Americans, Italians and other Europeans. University of Helsinki researchers examined the associations between coffee consumption and serum GGT levels in 60,323 Finnish participants between the ages of 25 and 74 who were cancer-free at the beginning of the study.

Participants were mailed a questionnaire about their medical history, socioeconomic factors, smoking habits and dietary habits. A subset of participants (n = 37,842) had clinical data available, including alcohol consumption and serum levels of GGT. Study participants were divided into five categories based on their response to the question “How many cups of coffee do you drink daily?”:

• Category 1:   0 — 1 cup
• Category 2:   2 — 3 cups
• Category 3:   4 — 5 cups
• Category 4:   6 — 7 cups
• Category 5:   8 or more cups per day

During a median follow-up period of 19.3 years, 128 participants were diagnosed with primary liver cancer.

The researchers observed that the cumulative incidence curve of liver cancer decreased with increasing amounts of daily coffee consumption (graph). When the analysis was restricted to surveys from participants that had clinical data available, a statistically positive association was found between serum GGT level and liver cancer risk. Joint association of coffee consumption and serum GGT level with liver cancer showed that participants who drank 0 — 1 cups of coffee and were in the top 25% of subjects sampled with respect to serum GGT had about 9.2 times increased risk for liver cancer compared to participants who drank at least 6 cups of coffee daily and were in the bottom 75% of subjects sampled with respect to serum GGT.

The study results are consistent with two meta-analyses published last year demonstrating an inverse relation between coffee consumption and liver cancer [7-8]. While a previous investigation found an inverse association between coffee consumption and serum GGT level, this study is the first large prospective study to suggest that a high level of serum GGT is a risk factor for primary liver cancer. The authors discuss a mechanism for the association between coffee drinking and serum GGT on liver cancer risk [1]:

Several other putative mechanisms behind the association of coffee drinking and serum GGT on liver cancer risk have also been proposed. Coffee contains many compounds, such as chlorogenic acid, which may have the potential to influence glucose metabolism processes to prevent hyperglycemia, and consequently oxidative stress.

Indeed, chlorogenic acid, a chemical largely responsible for coffee’s bitterness, may also be responsible for coffee’s effect on serum GGT level and, ultimately, coffee’s health benefits.

More information and support for patients with “Liver cancer” can be found at Organized Wisdom and MDJunction. Additionally, the American Liver Foundation, the nation’s leading nonprofit organization promoting liver disease prevention and liver wellness, provides research, education and advocacy for those affected by liver-related diseases.

References

1. Hu et al. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology. 2008 Jul;48(1):129-36. DOI: 10.1002/hep.22320
   View abstract

2. A Snapshot of Liver and Bile Duct Cancers. American Cancer Society. Atlanta, Ga. 2007.
3. Ferlay et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5. version 2.0. Lyon, France: International Agency for Cancer Research; 2004.
4. Casiglia et al. Unexpected effects of coffee consumption on liver enzymes. Eur J Epidemiol 1993;9:293-297.
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5. Tanaka et al. Coffee consumption and decreased serum gamma-glutamyltransferase and aminotransferase activities among male alcohol drinkers. Int J Epidemiol 1998;27:438-443.24.
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6. Wu et al. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92.
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7. Larsson and Wolk. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology. 2007 May;132(5):1740-5. Epub 2007 Mar 24.
   View abstract
8. Bravi et al. Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatology. 2007 Aug;46(2):430-5.
   View abstract

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As 2007 comes to a close, I would like to thank you for your readership. Just over one year ago, I launched two websites, Highlight HEALTH and the Highlight HEALTH Web Directory. Here at Highlight HEALTH, my goal was to write about biomedical research I found interesting and to make it easier for people to understand research findings, empowering them to have more productive discussions with their physicians and to make informed decisions about healthcare. The Highlight HEALTH Web Directory is my endeavor to catalog and make available health-related websites I find to be informative and useful. More recently, I’ve also started writing about Web 2.0 in Health, Fitness and Medicine, and plan to publish a series of review articles on a number of health-focused social networks.

This past month, I started the Highlight HEALTH Network, an aggregation of content from both sites to allow readers to keep up with the latest articles on Highlight HEALTH and the newest additions to the Highlight HEALTH Web Directory, all from a single source.

Here are the most popular articles for 2007 (top 20 based on the number of page views/number of days posted):

1. The Highlight HEALTH Network RSS Dashboard Widget
2. Smoking Cessation Timeline: What Happens When You Quit
3. Dichloroacetate Not Ready for Therapeutic Use
4. The Highlight HEALTH Network
5. New Common Cold Virus Variant Deadly
6. Common Therapy for Prostate Cancer May Promote Metastasis
7. Overweight Kids and TV: An Advertising Epidemic
8. Saline Nasal Irrigation More Effective than Spray for Chronic Sinus Symptoms
9. Pediatric Grand Rounds 2.8
10. The Genetics of Panic Disorder
11. Smoking Duration vs. Intensity and the Impact on Lung Cancer Risk
12. Social Networks and Health - The Research and the Reviews
13. Quercetin
14. American Obesity Rate Levels Off
15. Biodegradable Polymers for Drug and Gene Delivery
16. Individual Genetics, Coffee Consumption, BRCA1 and Breast Cancer
17. The Flu, Your Health and the Importance of Vaccination
18. SCHIP Funding and Fiscal Irresponsibility
19. DNA Amplification by Polymerase Chain Reaction (PCR)
20. Sinus Congestion

Thank you and Best of Health in the coming year!

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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.
   View abstract
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.
   View abstract
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.
   View abstract
8. Bae et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004 Nov 1;64(21):7893-909.
   View abstract
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.
   View abstract

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