The Clinical Research Of Prostate Biopsy Population And Preliminary Study Of Genistein In The Same Population

Prostate cancer (PCa) has become one of the most common malignant tumors in the western countries. It is estimated that nearly 914,000 men developed PCa and 258,000 died of this disease. The morbidity and mortality are relatively low in Asian, however, they are increasing rapidly due to the changes of people’s daily diet and environment, especially in developed metropolitan areas (for example,the morbidity in Shanghai has increased by 6 times since 1970s). The early detection is the key for curative treatment for PCa and the gold approval of diagnosis is still the transrectal ultrasound guided biopsy.In the late 1980s, Prostate-specific antigen (PSA) was introduced and was proofed to be significantly associated with PCa, then it was widely used in clinic for primary diagnosis of PCa. However, after years of application, limitations of PSA have been found because of its low specificity, which might cause quite a number of over-diagnoses and over-treatments. This might bring the burden to the patients and the economic of society. In recent years, a variety of prostate-specific biomarkers have been introduced and used to improve the diagnostic accuracy. Meanwhile, researchers turned to find new PCa biomarkers with higher specificity.As far as we know, risk factors of PCa including gene, environment and diet. According to the data from IARC, in 2002, the age-standardized morbility of PCa in Chinese is 1.6/100,000, as for Chinese American, the morbility is 80.4/100,000 and 159.9/100,000 for American Caucasian. The morbilities of American Caucasian and Chinese American are 100 times and 50 times more than Chinese respectively. The difference in morbility could not be explained by different screening strategies in two countries. Since Chinese and Chinese American share similar genetic background, we consider diet and environment factors may play a role in it.Genistein is one of the main soy isoflavone in our daily diet. People with different dietary structures have different serum genistein levels. Those with diet based on soy food have much higher serum genistein concentration than those with diet base on meat. There were some studies both in vivo and vitro had proved that high concentration of serum genistein may relate to the low morbidity and mortality of prostate cancer in Asian population, However, studies of genistein in Chinese population still lacks.Our objectives in this study are as following:(1) To discuss the relationship between age and biopsy result in Chinese prostate biopsy population; (2) To discuss the relationship between prostate volume and biopsy result in Chinese prostate biopsy population; (3) To preliminarily study the serum genistein level in Chinese prostate biopsy population. population, However, studies of genistein in Chinese population still lacks.PartⅠAge-specific Prostate Specific Antigen Cutoffs for guiding biopsy decision in Chinese PopulationBackground:Age-specific prostate specific antigen (PSA) cutoffs for prostate biopsy have been widely used in the USA and European countries. However, the application of age-specific PSA remains poorly understood in China.Methods:Between 2003 and 2012,1,848 men over the age of 40, underwent prostate biopsy for prostate cancer (PCa) at Huashan Hospital, Shanghai, China. Clinical information and blood samples were collected prior to biopsy for each patient. Men were divided into three age groups (≤60,61 to 80, and >80) for analyses. Digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total PSA (tPSA), and free PSA (fPSA) were also included in the analyses. Logistic regression was used to build the multi-variate model.Results:Serum tPSA levels were age-dependent (P=0.008), while%fPSA (P=0.051) and PSAD (P=0.284) were age-independent. At aspecificity of 80%, the sensitivities for predicting PCa were 83%,71% and 68% with tPSA cutoff values of 19.0ng/mL (age≤60),21.0ng/mL (age 61-80), and 23.0ng/mL (age≥81). Also, sensitivities at the same tPSA levels were able to reach relatively high levels (70%-88%) for predicting high-grade PCa. Area (AUC) under the receive operating curves (ROCs) of tPSA,%fPSA, PSAD and multi-variate model were different in age groups. When predicting PCa, the AUC of tPSA,%fPSA, PSAD and multi-variate model were 0.90,0.57,0.93 and 0.87 respectively in men≤60yr; 0.82,0.70,0.88 and 0.86 respectively in men 61-80yr; 0.79,0.78,0.87 and 0.88 respectively in men>80yr. When predicting Gleason Score≥7 or 8 PCa, there were no significant differences between AUCs of each variable.Conclusion:Age-specific PSA cutoff values for prostate biopsy should be considered in the Chinese population. Indications for prostate biopsies (tPSA,%fPSA and PSAD) should be considered based on age in the Chinese population.Part ⅡThe Influence of Prostate Volume on Cancer Detection in Chinese populationBackground:Prostate volume has been proved to be one of the strongest predictor of prostate cancer detection in biopsy in western population. To evaluate associations between prostate volume, PSA and prostate cancer detection in Chinese population, we performed this study in a biopsy cohort.Methods:Between 2007 and 2013,1,486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. Clinical information and blood samples were collected prior to biopsy. The study population were divided into two groups according to tPSA range (4 ng/ml<tPSA<20 ng/ml and tPSA>20 ng/ml) for analysis. Prostate volume (PV), age, total PSA (tPSA), Digital rectal examination (DRE) and transrectal ultrasound results (TRUS results) were included in the analysis.Results:Although the positive biopsy rates decreased in both tPSA range groups, the downtrend is more meaningful in 4 ng/ml<tPSA<20 ng/ml group. So we focus on 853 men in 4 ng/ml<tPSA<20 ng/ml group. In multivariate logistic regression analysis, Only DRE was found to be associated with PCa in four PV groups (P<0.05) and tPSA did not show a good predicting ability when PV exceeded 50 ml (P>0.05). Also, it may suggest that with PV increasing, the cancer detection risk decreased in men with different tPSA, DRE and TRUS nodule statuses (all P values for trend were<0.001).Conclusion:Our study indicate that in tPSA range from 4 to 20 ng/ml, prostate volume might be taken into consideration for biopsy decision in Chinese population.Part IIIPreliminary Study of Genistein in Chinese Prostate Biopsy PopulationBackground:Genistein is one of the main soy isoflavone in our daily diet. There were some studies both in vivo and vitro had proved that high concentration of serum genistein may relate to the low morbidity and mortality of prostate cancer in Asian population. Since there are few studies of genistein in Chinese population, we performed this study to preliminary evaluate the associations among serum genistein, epidemiologic factors and prostate cancer in Chinese population.Methods:Between 2012 and 2013,60 men over the age of 40, underwent prostate biopsy for prostate cancer (PCa) at Huashan Hospital, Shanghai, China. Clinical information, epidemiologic information and blood samples were collected prior to biopsy for each patient. All patients underwent 10-core ultrasound guided transperineal prostate biopsy, the pathology results were collected after biopsy. Measure the serum genistein concentration of the blood samples and analyze the results along with the clinical and epidemiologic information.Results:Among the 60 patients,27(45.0%) were diagnosed with prostate cancer. The serum genistein concentration of non-PCa patients (1223.7 ng/ml) were significantly higher than PCa patients (890.4 ng/ml) (P<0.05). As for other epidemiologic factors, we found significant difference in age (73.6 vs.68.9) (P<0.05) and smoking history (51.9% vs.24.2%) between PCa and non-PCa patients. In the univariate analysis, we found age and serum genistein were related with prostate cancer (P<0.05). In multivariate analysis, we found age,family history of cancer, smoking history and serum genistein were related with prostate cancer (P<0.05).Conclusion:High concentration of serum genistein may have a protective effect for prostate cancer.