April 13, 2004 Access past issues

Reviewed by: Jenny Rose Toledo Rollins School of Public Health Department of Epidemiology Emory University

The Health Outcome

Breast cancer is the most common form of cancer and the second most common cause of cancer deaths among U.S. women, with approximately 250,000 cases and 40,000 deaths per year(1). Many genetic and environmental elements are risk factors for breast carcinogenesis. Scientists have studied the genetic association of polymorphism in the metabolizing enzyme catechol-O-methyltransferase (COMT) to the risk of breast cancer. (2,3) These studies were performed amongst diverse populations and produced varying results. In most cases, low activity COMT L-L genotype was associated to higher risk of breast cancer. In a previous study, the authors found a significant inverse relationship between green tea intake and the risk of breast cancer among Asian-American women. (4) However, COMT has been found to rapidly metabolize the catechol-containing tea polyphenols through O-methylation. (5) These findings have lead to the study of the interrelationship of green tea consumption, COMT genotype, and the risk of breast carcinogenesis.(6)

The Finding

Wu et al. investigated the interrelationships among tea consumption, COMT polymorphisms, and breast cancer in Asian-American women in Los Angeles County through a population-based case-control study. This study focused on the risk of breast cancer among Chinese, Japanese, and Filipino ethnicity. The consumption of green and black teas were estimated separately and then combined. All three genotypes of COMT were compared (HH, HL, LL) and they created a fourth category combining genotypes with the presence of a low-activity allele (HL, LL).  They hypothesized that the tea catechins would be less rapidly metabolized in individuals with low activity COMT allele, and therefore these individuals would have increased benefits from tea consumption, whereas, individuals with high activity COMT allele would have rapid elimination of tea catechins and there would be less protective effect of tea consumption . However, this hypothesis depends on the assumption that methylated polyphenols are "less protective," where supporting evidence does not yet exist.

Observing solely the gene-disease association, the presence of a low activity COMT L allele was only significant among the Filipino ethnicity. However, measuring the joint impact of COMT genes and tea intake exposure, the presence of low activity COMT L allele and drinking tea is significantly protective with a 12.87% of the protective effect attributable to the combination of the presence of the COMT L allele and tea drinking. Through gene-environment interaction, COMT genotype may play opposing roles in breast cancer risk.

Public Health Implications

While there is much biological evidence to support the plausibility of interactions between COMT genotype and environmental exposures, there have been few studies to evaluate these associations. This study provides evidence of positive interaction between COMT genotype and tea drinking among Asian-American women. The authors offer their finding as a possible reason for conflicting results in the risks associated to COMT genotype in previous studies. Further studies with a larger sample size, a wider range of ethnicities, and testing the assumption that methylated polyphenols are less protective must be explored in the future.

References

1. CDC, August 30, 2002 . The Burden of Chronic Diseases and Their Risk Factors, 2002 CDC Accessed 3/13/2004 .
2. Thompson PA, Sheilds PG, Fruedenheim JL, Stone A, Vena JE, Marshall JR, Graham S, Laughlin R, Nemoto T, Kadlubar FF, Amrosone CB. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Research, 1998; 58:2107-2110.
3. Mintrunen K, Jourenkoa N, Kataja V, Eskelinene M, Kosma VM, Benhamou S et al. Polymorphic catechol-O-methyltransferase gene and breast cancer risk. Cancer Epidemiology, Biomark & Prevention, 2001; 10:635-640.
4. Wu AH, Yu MC, Tseng CC, Hankin J, & Pike MC. Green tea and risk of breast cancer in Asian-Americans. Int J Cancer, 2003; 106:574-579.
5. Zhu BT. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. Curr Drug Metab, 2002; 3:321-349.
6. Wu AH, Tseng CC, Van Den Berg D, Yu MC. Tea Intake, COMT Genotype, and Breast Cancer in Asian-American Women. Cancer Research, 2003; 63:7526-7529.