[Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages].

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

[Application values of genome-wide association studies in screening for breast cancer].

Objective: To investigate the potential application values of screening on breast cancer, using the single-nucleotide polymorphisms (SNPs) that were identified from the genome- wide association studies (GWASs). Methods: Two million Chinese women aged 35-69 years were simulated, based on both age distributions, age-specific incidence rates of breast cancer and the distribution of known risk factors, in 2013. Twenty-three SNPs identified from GWAS were further simulated. Both genetic-related risks explained by each SNPs and the improvement on the risks under reclassification, were used to select SNPs for the prediction on breast cancer among the targeted high-risk population. Further analyses were conducted to investigate the following items as: improvements on detection rates of breast cancer among the high-risk populations, areas under the curve (AUC) and the odds ratio (OR) among women at high risk. Results: A total of 12 SNPs were eligible for targeting the high-risk population of breast cancer. When high-risk populations were defined as women whose predicted risks were higher than the 95(th) predicted risk of the whole population, the detection rate (146.99/100 000) among high-risked women predicted by 12 SNPs would be significantly lower than 177.46/100 000, which was predicted by the known risk factors (P<0.001), among the high-risked women. Among those women at high risk, the detection rate (229.00/100 000) predicted by integrating known risk factors and 12 SNPs was significantly higher than that predicted by known risk factors (P<0.001). Also, the AUC increased from 64.4% to 67.8% (P<0.001), and the OR of increased from 3.32 to 4.33, predicted by integrating known risk factors and 12 SNPs, for women at high risk on breast cancer. Conclusion: Targeted SNPs that were identified from genome- wide association studies could be used to improve the detection rates as well as the overall accuracy of risk prediction so as to identify the potential high-risk women on breast cancer before carrying on the screening program.

Expression of Wnt-1 and TSLC1 in condyloma acuminatum.

BACKGROUND: Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for condyloma acuminatum (CA) have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development. AIM: To investigate the expression and significance of the proteins Wnt-1 and TSLC1 in patients with CA and in normal foreskin controls. METHODS: Wnt-1 and TSLC1 were assessed by immunohistochemistry in 45 patients with CA. RESULTS: Positive expression rates of Wnt-1 and TSLC1 were 82.22% (37/45) and 37.78% (17/45), respectively, in CA tissues, and 29.17% (7/24) and 91.67% (22/24), respectively, in normal foreskin controls. Wnt-1 expression intensity in CA was markedly higher (positive to strongly positive) than that in normal controls (negative to weakly positive), whereas TSLC1 expression intensity ranged from weakly positive to positive in CA, and nearly strongly positive in the normal control group. The differences in the positive expression rate and expression intensity of Wnt-1 and TSLC1 between the two groups were statistically significant (P < 0.05). In addition, Wnt-1 and TSLC1 were negatively correlated. (r = -0.336, P < 0.05). CONCLUSIONS: Overexpression of Wnt-1 and low expression of TSLC1 may be associated with the growth of CA. These findings may provide a basis for the development of therapies to prevent recurrence or malignant transformation of CA.

[Overdiagnosis in mammography screening for breast cancer].

Screening has been always considered as a double-edged sword. Cancer screening could save lives in some cases, however, in other cases, it might also turn people into overdiagnosis. Overdiagnosis is the diagnosis of cancer that will never cause symptoms or death during a patient's lifetime. Therefore, overdiagnosis might lead to unnecessary treatments and lifetime surveillance, and then increase economic burden and psychological burden. In this review, we focus on how to correctly evaluate the overdiagnosis rate, and how to avoid or reduce the harms caused by overdiagnosis in the future according to the reasons associated with overdiagnosis. After systematically reviewing the previous studies, we will try to identify the potential reasons associated with overdiagnosis in breast cancer screening with mammography, address how to correctly evaluate the overdiagnosis rate, and finally provide some suggestions to reduce the overdiagnosis.