Study Of The Dietary Intake Levels, Fatty Acid Lipid Metabolic Gene Expressions And Their Relationships With Breast Cancer Risk

Breast cancer, the most common malignancy tumor in women, severely threatens women's health and life. According to the report of American Cancer Society, about 1.3 million new cases of invasive breast cancer were diagnosed among women worldwide in 2007, and 465,000 women were died from breast cancer. Breast cancer has the highest incidence rate than the other malignant tumors among women in the developed countries, such as in Western Europe and North America. In 2009, an estimated 192,370 new cases of invasive breast cancer were diagnosed among women in US, and approximately 40,170 women were expected to die from breast cancer. Chinese women had traditionally lower incidence of breast cancer in the past. However, with the change of life style and dietary structure in the recent twenty years, breast cancer incidence has been increased by 3% per year in China, accompanied by the largely increased breast cancer mortalities. At the same time, the age of women who developed breast cancer became younger than before. Obviously, Breast cancer has imposed heavy burdens on the patients and society.To decrease the incidence rate of breast cancer, extensive studies has been conducted on the pathogenesis, early diagnose and preventive methods of breast cancer at home and abroad. Large animal experiments and cohort studies indicated that breast cancer has a close relationship with dietary factors, especially in dietary fat. However, further studies suggested that saturated fatty acid (SFA), monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) had different effects on the breast carcinogenesis. Furthermore, different ratio of n-3/n-6 PUFA had different effects on the breast carcinogenesis. Although large quantities of researches had been conducted on the relationship between dietary nutrition intake and breast cancer risk, the relations between dietary fatty acid and breast cancer is still unclear due to different dietary mode, diversity of food composition and complexity of food intake estimation. With the deepening research on the Lipid Research Group, researchers have the further understanding on the fatty acid function, lipid metabolism regulation and their corresponding molecular mechanisms on disease. Study suggests that different dietary fatty acids have different effects on breast cancer, may be related to changes in body tissue fatty acid composition, thereby affecting lipid metabolism and function. As the lipid metabolism regulation of key genes, fatty acid synthase (FAS), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and peroxisome proliferator-activated receptor-γ(PPAR-γ) can affect breast cell proliferation, differentiation or apoptosis thus play important roles in the development of breast cancer. However, previous researches were restricted to tumor cells in animal experiments and in vitro experiments. In consideration of the changes of dietary structure in China, the evaluation of the relationship between lipid metabolism expression and breast cancer on population level may help to further understand the potential molecular mechanism of dietary fatty acids and lipid metabolism on the development of breast cancer.This project was designed to mainly evaluate the relationships among dietary fatty acid, lipid metabolism and breast cancer. A case-control study was carried out in Chongqing, China. Totally, 458 newly incident and histologically confirmed breast cancer and 789 healthy controls were enrolled into our study from February 2004 to December 2006. Subjects were divided into the premenopausal and postmenopausal group according to their menstrual status. All of the eligible participants were Chongqing female residents and consent to participate in our study. Semi-quantitative food frequency questionnaire table was used to investigate the dietary pattern and fatty acid intake in the recent year. Software SPSS 13.0 was applied to analyze the difference of fatty acid levels between different groups, and to evaluate the associations of breast cancer risk with dietary fatty acid intake levels. At the same time, breast cancer tissues and adjacent non-cancerous tissues were spontaneously collected from 65 breast cancer patients. The expressions of FAS, Cox-2, 5-LOX and PPAR-γmRNA were detected by RT-PCR. We also determined the expression of lipid metabolic genes in breast cancer tissues, and the evaluated the potential roles of the lipid metabolic regulation in the effects of different dietary fatty acids on the development of breast cancer. Main results1. Dietary fatty acid intake and its relevance to the breast cancer There was no difference in SFA and n-3 PUFA intake among the three groups both in pre- and post-menopausal women. However, the intake of MUFA (mainly C18:1) in the breast cancer group were significantly lower than the healthy controls while n-6 PUFA (mainly C18:2) intake and ratio of n-6/n-3 were significantly higher than controls. Further analysis indicated that MUFA, n-6 PUFA intake and ratio of n-6/n-3 could significantly influence the incidence of breast cancer.2. Expressions of lipid metabolic genes in breast cancer tissues and their relationships with dietary fatty acid intakes2.1 Expressions of FAS, Cox-2, and 5-LOX in breast cancer tissues were significantly higher than those in adjacent tissues (FAS and 5-LOX, P<0.01; Cox-2, P<0.05). There was no significant difference of PPAR-γexpression between the two groups (P>0.05).2.2 The expression of FAS in breast cancer tissues was significantly negatively correlated with dietary C16:0 intake levels (Pearson correlation, -0.376) and positively correlated with dietary C18:0 intake levels (Pearson correlation, 0.274). At the same time, the expressions of Cox-2 were significantly positively correlated with dietary C18:0 and C18:2 intake levels (Pearson correlation, 0.318 and 0.261), and 5-LOX expressions were also significantly positively correlated with dietary C18:2 and C18:4 intake levels (Pearson correlation, 0.195 and 0.227). No substantial correlations were shown between PPAR-γexpressions and dietary fatty acid intakes.In summary, through the above population study and experiments, our project evaluated the associations of dietary fatty acid intake, lipid metabolic gene expressions with breast cancer risk. We observed that sufficient dietary MUFA intake might effectively prevent the breast cancer, while dietary n-6 PUFA intake and increased ration of n-6/n-3 might increase the risk of breast cancer. At the same time, the increased expressions of FAS, Cox-2 and 5-LOX could enhance the risk of breast cancer, and their expressions were significantly correlated with dietary fatty acid intakes. In consideration of the residents'current dietary structure, the above results suggested that women should control the intake level of total fat and total SFA, reduce the intake of n-6 PUFA and assure the intake of n-3 PUFA, MUFA, so as to eventually prevent breast cancer from behavior and dietary pathways. Besides, lipid metabolic pathway play an important role in the development of breast cancer, and the diverse effects of different fatty acids on breast cancer might partly derived from their corresponding regulations on lipid metabolic pathway.