Associations Between Soy Isoflavones,Dietry Pattern,Vitamin D Metabolism Related Genes And Female Breast Cancer

ObjectiveBreast cancer is one of common cancers among female,and the 14%of cancer deaths were caused by it.Although the incidence of breast cancer was rising in Asia countries in the past decades,incidence and mortality of breast cancer in Western countries were higher than Asian countries.Migrant studies have found that persons who move from low to high incidence areas were also at increased risk of breast cancer,this suggested that environmental factors,including diet,may play an important role in breast cancer development.Soybean and its products are rich in phytoestrogens,the main form of soybean isoflavones.In this study,we calculated the intake of isoflavones by collecting dietary data from participants and analyzed their relationship with breast cancer in accordance with menopause status,body mass index(BMI),waist circumference(WC),as well as the interaction between above mentioned factors.In this study,we also analyzed and the daily diet intake of study participants and summarized four main dietary patterns,and their associations with the risk of breast cancer in women.In addition,as Vitamin D treatment may have significant effect on female breast cancer.In this study,the polymorphisms of vitamin metabolic receptors(VDR)and cluster-specific components(GC proteins)in the metabolic process of vitamin D were analyzed to improve the understanding between single nucleotide polymorphisms of related genes and breast cancer.MethodUsing the data from local population-based cancer registry agency,newly diagnosed primary breast cancer patients in Wuxi City from 20**to 20**were recruited as cases(n=818).Controls(n=935)were derived from the same area as cases.Controls and cases were frequency matched by age(±5 years).Eligible controls were randomly selected from the general population,using the data of electronic population health records.Individuals with history of cancer were excluded.Using standard protocols and a pre-tested questionnaire,with written informed consent signed,epidemiological data were collected by trained investigators through face-to-face interviews.A Food Frequency Questionnaire(FFQ)was used to collect information of individual food consumption in the previous 12 months by a face-to-face interview.Physical examination including anthropometric measurements,B-ultrasound for breast and abdomen,and mammographic test were also conducted at the time of interview.In addition,10 ml of fasting blood samples were collected for laboratory analysis.Genomic DNA was extracted from 200?l of peripheral blood using QIAamp DNA Blood Mini Kit(QIAGEN,Germany)following the manufacturer's instructions.Assay design and SNP genotyping were performed using the Sequenom Mass ARRAY platform provided by CapitalBio(Beijing,China).Soy isoflavones in each food was calculated by The Chinese Food Composition.The principal component analysis was used to summarize the dietary pattern.T-test was used to compare the differences of continuous variables,while Pearson ?2 test was applied to compare the differences of categorical variables between cases and controls.The odds ratio(OR)and 95%confidence interval(CI)were calculated using unconditional logistic regression.Result1.Large intake of soy isoflavones could significantly reduce the risk of breast cancer in postmenopausal women(OR:0.54,95%CI:0.34-0.87,P-trend<0.05).Stratified by BMI and WC the protective effect of soybean isoflavones on breast cancer was only observed for central obesity and female population with BMI less than 28 kg/m2,showing significant linearity in women with BMI<24 kg/m2 Trend(P-trend<0.05).2.The traditional Chinese dietary pattern(characterized by a relatively balanced intake of nutrients)and sweet pattern can reduce the risk of breast cancer in women,while the prime model and salty pattern were not found to be associated with breast cancer.3.Genetic polymorphisms ofrsl 1568820,rs11608702,rs12721364 and rs2239186 of VDR could influence the risk of breast cancer in women.The rs11608702 and rs2239186 were confined to postmenopausal women,OR(95%CI)was 1.88(1.16-3.04),1.39(1.01-1.92).The VDR gene rs11608702 was observed in the dominant mutation pattern(OR:1.56,95%CI:1.08-2.27).At the same time,the CT and TT genotype of rs11568820 showed a lower risk of breast cancer(OR:0.73,95%Cl:0.58-0.91)compared with CC genotype in recessive mode.In this study,DBP-related genes were not found to be significantly associated with female breast cancer.ConclusionThis population-based case-control study explored the relationship between soybean isoflavones,dietary patterns and vitamin D metabolic pathways related genes and breast cancer.The study found that high soy isoflavones intake in postmenopausal women showed protect effect on breast cancer.At the same time,BMI and WC stratified analysis showed that the protective effect of soybean isoflavones was more obvious in female population with central obesity and BMI less than 24 kg/m2.The traditional Chinese dietary pattern and sweet pattern could significantly reduce the risk of breast cancer.In addition,genetic polymorphisms of VDR rs11568820,rs11608702,rs12721364 and rs2239186 may associated with reduced risk of breast cancer,while the protective role of rs11608702,rs2239186 were only observed among postmenopausal women.VDR gene rs11608702 was observed in dominant mutation model,while in the recessive mode,CT and TT genotype of rs11568820 showed a lower risk of breast cancer compared to CC genotype.In this study,GC related genes were not found to be significantly associated with female breast cancer risk.