Analysis On Physical Activity,Obesity,and Related Gene Polymorphism With The Risk Of Breast Cancer

ObjectiveBreast cancer is the most common malignancy among women all over the world and causes huge social and economic burden.Many factors can increase the risk of breast cancer,body fatness,physical activity have been considered as important risk factors especially among postmenopausal women.Genetic factors,for instance,genes encode proteins and enzymes which are important in various biological processes,may impact individual susceptibility by different pathways,such as obesity-related genes.In addition,levels of biochemical and tumor markers may help to establish the diagnosis of breast cancer.Thus,We conducted an population based case-control study aim to identify the effect of obesity-related genes and physical activity on breast cancer occurrence,and their interactions with body fatness on breast carcinogenesis,as well as the association between biochemical and tumor markers with breast cancer among Chinese women.These findings will improve the understanding of the etiology of breast cancer in China.Methods1.A population-based case-control study of breast cancer was conducted from 2013 to 2014 in Jiangsu Province,China.A total of 818 newly diagnosed primary breast cancer cases and 935 controls were recruited by a standard questionnaire.Epidemiological data such as demographic information were collected by face-to-face interview.Anthropometric measurements including height,weight,waist circumference,and hip circumference were conducted at the time of interview.The physical activity data were collected by face to face questionnaire which adapted from the Global Physical Activity Questionnaire(GPAQ).The overall and menopausal specific effects for physical activity were evaluated by unconditional logistic regression.The strength was quantified as odds ratios(OR),and 95%confidence intervals(CI).Statistical interactions between physical activity and body fatness on breast cancer risk were assessed on both additive and multiplicative scales.2.A total of 797 newly diagnosed primary female breast cancer patients and 930 matched controls were recruited in this study to examine serum levels of 15 biochemical markers and 4 tumor markers.Sera isolated from human blood samples were immediately sent to the lab and kept in-20℃ for 24 hours.The entire machines applied in biomarkers detection and analyses were provided by the Clinical laboratory of KingMed Diagnostics,China.3.DNA was isolated from blood samples and genotype identification was set up using proposed assays.Analysis of selected genotype of RAS p21 protein activator 2(RASA2)rs 16851483,cell adhesion molecule 1(CADM1)rs 12286929 and hypoxia inducible factor 2 alpha subunit inhibitor(HIF1AN)rs 17094222.Unconditional Logistic Regression Model were applied for estimating the parameters of the associated factors,including adjusted odds ratio(OR1),further adjusted odds ratio(OR2)and 95%confidence interval(95%CI).The interaction between genes and body fatness of breast cancer also been analyzed for our study.Results1.Physical activity in work was found to associate with the risk of overall breast cancer.Vigorous intensity and none of activity at work increased breast cancer risk,especially in post-menopausal women,with an OR of 2.25(95%CI:1.30-3.89)and 1.74(95%CI:1.16-2.60).Moreover,compared with 56-168 MET-h/week physical activity in work,a protective effect was found in post-menopausal women with vigorous level physical activity(168-MET-h/week:OR=2.07,95%CI:1.16-3.70;none:OR=1.81,95%CI:1.16-2.81).However,we did not found association between physical activity in commuting and recreational activity with breast cancer.In addition,the interaction between physical activity and body fatness was detected as well.2.For circulating biochemical indexes,elevated levels of serum lipid components were associated with increased risk of breast cancer,including low-density lipoprotein cholesterol(LDL-C)(OR = 1.41,95%CI:1.06-1.87),triglyceride(TG)(OR = 2.71,95%CI:2.06-3.55),apolipoprotein A1(ApoAl)(OR = 2.97,95%CI:1.45-6.08),apolipoprotein B(ApoB)(OR ＝1.55,95%CI:1.20-2.00),elevated glucose(GLU)(>7.0 mmol/L)(OR =2.25,95%CI:1.57-3.24)and high sensitivity C-reactive protein(hsCRP)(>5 mg/L)levels(OR = 1.73,95%CI:1.06-2.82).For tumor biomarkers,serum concentrations of carcinoembryonic antigen(CEA)and carbohydrate antigen 125(CA125)appeared to be strongly related to breast cancer risk depending on individual’s menopause status3.The three genetic variations related to obesity were involved in this study.Significant differences were observed in the distribution of RASA2 rs 16851483 T/T homozygote and CADM1 rs12286929 G/A heterozygote genotypes between cases and controls,with an OR of 1.68(95%CI:1.10-2.56)and 0.80(95%CI:0.64-0.99),respectively.An association between the HIF1AN rs17094222 T/T and T/C + C/C genotype and the risk of breast cancer was not observed.A significant interaction was observed between genetype and body fatness on both the additive and multiplicative scaleConclusionBreast cancer has become a significant public health problem in China.In conclusion,the main findings of this study indicate that female cancers,mainly breast cancer,are becoming more significant public health issues among Chinese women.The quick economy development and subsequently caused significant lifestyle and environmental change could be the main reasons.At individual level,high body fatness such as high BMI,WHR and WC,physical inactivity,high blood glucose and blood lipids etc.are associated with the risk of breast cancer.Besides,Hereditary determinants such as family history of cancer among first degree relatives and genetic polymorphisms of related genes in different pathways may also influence the individual susceptibility of cancer and could modify the risk of high body fatness and physical activity.As the majority of risk factors found in this study are modifiable,these could be translated into risk reduction of breast cancer in China.