Faculty Bibliography

Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the promoter region, with the variant A allele conferring lower transcription activity than the common G allele. Because oxidative stress may play a role in breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer Study Project (1996-1997). We also assessed the potential modifying effects of dietary antioxidants and hormonally related risk factors on these relationships. Women over 20 years with incident breast cancer who were residents of Nassau and Suffolk Counties, NY, were identified as potential cases. Population-based controls were frequency matched by 5-year age groups. Genotyping was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) technology, and suspected breast cancer risk factors and usual dietary intake were assessed during an in-person interview. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Having at least one A allele was associated with an overall 13% reduction in breast cancer risk. When consumption of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations with either GA or AA genotypes were most pronounced among women who consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95% confidence interval, 0.58-0.97); this association was not noted among the low-consumption group (P for interaction = 0.04). Relationships were strongest among premenopausal women. Results from this first study of MPO genotypes and breast cancer risk indicate that MPO variants, related to reduced generation of ROS, are associated with decreased breast cancer risk, and emphasize the importance of fruit and vegetable consumption in reduction of breast cancer risk

omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer