Association between Metabolic Syndrome and tumor histologic grade and pathologic stage of bladder cancer

Bladder cancer is one of the most common malignancy of the urinary system,ranks among the 10 highest incident cancers worldwide. It’s a leading cause of cancer-related deaths [1]. The data which provided by the International Agency for Research on Cancer in 2012 suggested that 55,486 cases and 26,820 deaths were estimated for the population in the People’s Republic of China, accounts for a large proportion of bladder cancer in East Asia (85,451 cases and 37,491 deaths). Several risk factors are directly associated with an increased risk of bladder cancer, such as smocking and occupational exposure [2]. Besides, some studies have reported that obesity is involed in the increased risk of incident bladder cancer [35]. Extensive epidemiological evidence suggests that obesity is associated with an increased risk of cancer, while physical activity can reduce the risk of cancer [6], but bladder cancer is not always associated with body size or physical activity [7]. However, little data are available with regard to Body Mass Index (BMI) and the tumor grade and stage of bladder cancer.In epidemiological studies examining obesity and bladder cancer [8-22], no statistically signifi cant association was found in most populations [3,9-11,13,15-18,20-22]. Although three prospective studies [8,12,14] and a large case-control study Abstract

Citation: Jiang [19] had found a positive association between obesity and the risk of bladder cancer, only one [14] of these studies examined the association in detail.
As we all know, Metabolic Syndrome (MetS) is a complicated disorder described as a cluster of abnormal metabolic factors related to excess calorie intake and sedentary lifestyles. To our knowledge, MetS is characterized by overweight, blood glucose, hypertension, and dyslipidemia, which has become a global health problem with growing prevalence. With the improvement of living standard, the incidence and prevalence of obesity continues to rise. The Body Mass Index (BMI) is an important international measure of obesity and health.
Association beetween BMI and outcomes after surgery has been reported; however ,there is a limited large-sample research to evaluate the relationship between the BMI and grade and stage of malignancy of bladder cancer in a Chinese population. In our study, we investigated the relationship between the grade and stage of malignancy of bladdeer cancer and BMI and Mets in a Chinese population.

Results
As showned in the

Discussion
In recent years, a number of epidemiological studies have shown that the patients with MetS in a Chinese population were found to have statistically signifi cant with the occurrence and development of urinary tract diseases, and a large number of research confi rmed that MetS was signifi cantly associated with the pathogenesis and prognosis of prostate cancer. However, there are few information was available on the association between MetS, as well as the components of MetS, and bladder cancer.
Why is Mets associated with the pathogenesis and prognosis of the bladder cancer? Mets can reduce insulin sensitivity and lead to permanent insulin excess [23]. In addition, our report suggests that high BMI levels may be a risk factor for upper stage of bladder urothelial carcinoma.
The link mechanism between MetS and cancer risk is not fully understood. However, some MetS components have been extensively studied as risk factors for cancer. Increasing evidence shows the negative impact of obesity on genitourinary malignancies [24]. Some epidemiological studies have shown a positive correlation between obesity and increased bladder cancer risk, although other studies have not found any signifi cant associations [7,14].   Obesity is closely related to many major chronic diseases, including coronary heart disease and tumors, and has become a global public health problem. Studies have shown that overweight/obesity is an important cause of diabetes, and weight status in early adulthood and weight changes in middle age can increase the risk of chronic diseases such as diabetes and coronary heart disease. Increased body size and physical inactivity are associated with an increased risk of several cancers, but there are few studies suggested the relationship between Body Mass Index (BMI) and bladder cancer. So, in addition to the analysis of the relationship between MetS and bladder cancer, we researched the association between the BMI≥25.0 which as an individual factor and bladder cancer. As was shown in the Tables 2,3, we can found that BMI was sigifi cantly associated with bladder cancer including the tumor histologic grade and pathologic stage in a Chinese population. The positive correlation between BMI and bladder cancer was independent of other known bladder cancer risk factors, including age, race, and smoking, implying that avoiding obesity may play an important role in bladder cancer prevention.
Obesity exerts an infl uence on the condition of the metabolic which it can cause downstream metabolic changes, such as infl ammation, higher insulin levels, insulin-like growth factor production, and changes in sex hormones, all of these factors are related to cancer [26,27]. However, obesity and MetS are complex problems in the elderly. With the growth of age, the body will have some changes, such as the decrease of height, the decrease of muscle, the increase of fat in insulin resistance area, etc., but BMI is often not so accurate.(such as visceral, subcutaneous, intramuscular, and intrahepatic fat) [28]. With age, sarcopenia or sarcopenia is particularly important as it results in insulin resistance and MetS.
On the contrary, older adults are subject to the"Obesity Paradox" in which certain outcomes,such as survival,compared with normal weight or morbidly obese patients, obese patients have better curative effects.Research on other malignancies has shown that there is an Obesity Paradox, despite limited data specifi c to older people [29][30].

Conclusion
Our research implying that the MetS and obseity had associstion with the bladder caner, not only the tumor pathologic stage but also the histologic grade. In other words, when the patients are considered MetSs, they were found to have statistically signifi cant higher T stage and histologic grade of bladder cancer.

Author contributions
STZ and YG designed this study; SJ performed the statistical analysis and drafted the manuscript; and QFX, KD, ZHX, and YG, collected the data and helped design the manuscript. All authors read and approved the fi nal manuscript.