| 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. 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. According to the recent foundings, health education, chemoprevention and prophylactic surgery can significantly lower the incidence of breast cancer among those people who were at higher risk of breast cancer, and subsequently improve their quality of life. Therefore, researchers are engaged to establish and modify the risk predict mode for breast cancer, and to effectively screen the women at higher breast cancer risk from the general population through confirming and inducing the risk factors and biomarkers of breast cancer. These achievements are expected to provide rational advice on the hormone replacement therapy, routine breast examination, or essential chemoprevention and prophylactic surgery on these women.According to the comprehensive etiology studies of breast cancer, the established conventional risk factors of breast cancer are believed to include age, family history of breast cancer, history of breast benign diseases, dietary factors, reproductive factors, social factors and sex hormones. However, these data were mainly obtained from Caucasian women. In our country, there were much fewer studies on breast cancer etiology. Due to the differences of study population, research protocols, sample size and statistical method among these researches, the findings lack uniformity. Consequently, it is still unclear whether racial inheritance affects the relationship between conventional risk factors and breast cancer risk. In addition, 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. As a result, the study on the risk factors of breast cancer among Chinese women and evaluation on the relationship between dietary fatty acid intake levels and breast cancer risk has important significance on the dietary and behavior prevention of breast cancer.This project was designed to mainly evaluate the relationship between dietary fatty acid and women health. A case-control study was carried out to explore the conventional risk factors of breast cancer and breast benign disease. A total of 458 newly incident and histologically confirmed breast cancer, 392 breast benign disease patients 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. Gas chromatography was used to determine the plasma fatty acid composition, and the electrochemiluminescene immunoassay (ECLIA) technique was used to determine plasma sex hormone levels. Software SPSS 13.0 was applied to analyze the difference of fatty acid and sex hormone levels among different groups, and to evaluate the associations of breast cancer risk with plasma fatty acid compostion and sex steroid hormone levels. At the same time, animal experiment was conducted to study the intervention effect of the different fatty acid composition dietary (SFA,MUFA,n-6 PUFA,n-3 PUFA,1:1 n-6/n-3,5:1 n-6/n-3,10:1 n-6/n-3 and 1:2:1 S/M/P) on the incidence of the MNU induced breast cancer. We also determined the plasma fatty acid composition using gas chromatography and explored the underlying mechanism of different fatty acid compositions on the mammary carcinogenesis.Main results1. Population study1.1 Study on the conventional risk factors of breast cancer: Our study suggested that higher education extent, mental depression, older at first live birth, with breast benign disease history and with family history of breast cancer were the risk factors of breast cancer among both pre- and post-menopausal women. Besides, higher BMI value, higher WHR value, longer duration of menstruation and with history of reproductive disease could also significantly increased the breast camcer risk among postmenopausal women. On the contray, better human relationship, older at menarche, longer duration of breastfeeding could effectively decrease the risk of breast cancer. Similar to breast cancer, factors affecting benign breast disease include higher education degree, spirit hurt, longer cumulative duration of lactation, longer duration of menstruation, history of reproductive disease and family history of breast cancer.1.2 Plasma sex hormone levels and risk of breast cancer: Study period was divided into follicle phase, luteal phase and postmenopausal period here. We observed that levels of estrodiol in three periods, progesterone in the luteal phase, testosterone in the postmenopausal women were significantly higher than the respective healthy controls (P< 0.05). Furthermore, we observed significantly positive associations with the risk of breast cancer for estrodiol in all periods, progesterone in the luteal phase and testosterone in the postmenopausal period. Higher level of estrodiol in the luteal phase and in the postmenopausal period could also increase the incidence risk of breast benign disease.1.3 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. While the MUFA, n-6 PUFA intake and ratio of n-6/n-3 had significant correlation with breast benign disease only in the postmenopausal women. In addition, We observed the corresponding protective effects of dietary fiber, Ca, Zn, Vit C and carotene on the incidence of breast cancer and breast benign disease.1.4 Plasma fatty acid composition and its association with breast cancer risk: We observed high plasma levels of C16:0 and C18:1 were protective factors, while C18:2 and the ratio of n-6/n-3 were the risk factors of breast cancer both in pre- and post-menopausal women. We also observed that high plasma level of C18:0 could significantly increase the incidence risk of breast cancer in premenopausal women. Plasma levels of C18:1 and C18:2 and the ratio of n-6/n-3 could significantly influence the incidence risk of breast benign disease in post-menopause women.2. Animal intervention experiment2.1 SD rat mammary carcinogenesis model replication: The SD female rats (50 days old) of SPF grade were given MNU 50mg/kg once through intraperitoneal injection. The replication of SD rat mammary carcinogenesis model was confirmed by histopathology observation.2.2 The effects of different fatty acid composition intervention on the incidence of MNU induced mammary tumors: The incidence rate and multiple sites incidence rate of mammary tumors were significantly lower in rats of 1:1 n-6/n-3 group than those in groups of SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P. We did not observed the breast carcinogenesis in rats of n-3 PUFA group.2.3 The effects of different fatty acid composition intervention on the plasma fatty acid composition: The intervention of different dietary fatty acid could significantly influence the plasma fatty acid composition in rats, and the compositions were changed according to the corresponding mode of dietary fatty acid. Compared with n-3 PUFA group and 1:1 n-6/n-3 PUFA group which had no breast carcinogenesis or low breast tumor incidence, the plasma level of C18:0, C18:2 and ratio of n-6/n-3 increased significantly while the plasma level of EPA and DHA reduced significantly in the other groups with high mammary tumor incidence. The above results suggest that the changes of plasma fatty acid compositions might be the important factors to affect the incidence of mammary tumor.In summary, through the above population study and animal experiment, our project investigated the risk factors of breast cancer in Chongqing, evaluated the associations of dietary fatty acid intake, plasma fatty acid composition and plasma sex hormone levels with breast cancer risk. We observed that higher education extent, mental depression, higher BMI values, longer duration of menstruation, history of breast benign disease, family history of breast cancer, history of reproductive disease, higher levels of estradiol and testosterone were the important risk factors of breast cancer in Chongqing women. Besides, good human relationship, older at menarche, and longer duration of breastfeeding were the protective factors of breast cancer. The risk factors influencing the breast benign disease were similar with those influencing the breast cancer. Dietary factors are also closely related with breast cancer risk both in pre- and post-menopause women. Dietary fiber, Ca, Zn, Vit C, carotene and 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. The above factors could influence breast benign disease risk in postmenopausal women as well. Combined with the results of dietary fatty acid intake, plasma fatty acid composition and animal experiment, we found that MUFA and n-6 PUFA levels are closely related with breast cancer risk. Besides, the unbalanced ratio of n-6/n-3 in dietary intake and plasma fatty acid composition might also be the important risk factor of breast cancer and breast benign disease. In consideration of the residents'current dietary structure and life style, the above results suggested that women should keep good mental state and reasonable life style (including possible selection of menstruation and reproductive style). At the same time, basing on the rational dietary structure, they 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 and dietary fiber, so as to eventually prevent breast cancer from behavior and dietary pathways.
|
PDF Full Text Request