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Background: Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship. Objective: To reveal the causality between BMR and EC and OC, we performed the first comprehensive two‐sample Mendelian randomization (MR) analyses. Methods: Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium and Ovarian Cancer Association Consortium respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results. Results: BMR was significantly related to an increased risk of EC (ORSD = 1.49; 95% CI: 1.29–1.72; p‐Value <.001) and OC (ORSD = 1.21; 95% CI: 1.08–1.35; p‐Value <.001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (ORSD = 1.45; 95% CI, 1.23–1.70; p‐Value <.001), clear cell ovarian cancer(CCOC) (ORSD = 1.89; 95% CI:1.35–2.64; p‐Value <.001) and endometrioid ovarian cancer risk (EOC) (ORSD = 1.45; 95% CI: 1.12–1.88; p‐Value =.005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high‐grade serous ovarian cancer (HGSOC) and low‐grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses. Conclusion: The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC and LGSOC. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative cancer pain imposes severe physical and psychological problems. We aimed to investigate the pain experiences of patients with cancer after surgery, analyze the impact of infusion volume by patient-controlled analgesia (PCA), and explore the variations between day 1 and day 2. Methods: Data were retrospectively extracted from a large health data platform. Descriptive statistics were presented for the demographic and clinical profiles of patients. Multiple logistic regression analyses were performed to evaluate associations between intensity of pain and PCA use after adjustment for risk factors. Results: Among 11,383 patients with cancer, the incidence of pain (moderate to severe pain) was 93.3% (18.3%) at the first 24 h after operation, while the respect values decreased to 91.1% and 9.5% at the second 24 h. Further, female patients consistently experienced higher risk of pain over the whole 48 h postoperatively. Surgical sites were related to pain risk, with the highest risk among the respiratory system (OR 2.077, 95% CI 1.392–3.100). High doses of continuous volume (OR 2.453, 95% CI 1.742–3.456) and total volume (OR 2.830, 95% CI 2.037–3.934) of infusions were related to 1–3-fold elevated pain risk. Additionally, the observed associations were mostly repeated and could be up to over 10 times when pain was evaluated with number of PCA pump compressions instead of Numerical Rating Scale (NRS). Conclusions: High risk of postoperative cancer pain, particularly among the high PCA dose group, could possibly indicate inadequate pain control, and presence of modifiable risk factors warrants more aggressive pain management strategies perioperatively. [ABSTRACT FROM AUTHOR]

Background: A fundamental principle of pain management is to determine the distribution and causes of pain. However, relevant data among postoperative cancer patients based on a large amount of data remain sparse. Objective: We aimed to investigate the incidence of postoperative pain in cancer patients and to explore the associated risk factors. Methods: We retrospectively collected information on postoperative pain-evaluation records of cancer patients who underwent surgery between 1 January 2014 and 31 December 2019. Descriptive statistics were presented, and multinominal logistic regression analysis was performed to explore the risk factors associated with postoperative pain. Results: Among the 11,383 patients included in the study, the incidence of mild/moderate to severe pain at the 24th hour after surgery was 74.9% and 18.3%, respectively. At the 48th and 72nd hour after surgery, the incidence of mild pain increased slightly, while the incidence of moderate to severe pain continued to decrease. Female patients experienced a higher risk of pain (ORs: 1.37–1.58). Undergoing endoscopic surgery was associated with a higher risk of pain (ORs: 1.40–1.56). Patients with surgical sites located in the respiratory system had a higher risk of pain compared to in the digestive system (ORs: 1.35–2.13), and other patients had a relatively lower risk of pain (ORs: 0.11–0.61). Conclusion: The majority of cancer patients experienced varying degrees of postoperative pain but may not receive adequate attention and timely treatment. Female, young age and endoscopic surgery were associated with increased pain risk, and effective identification of these high-risk groups had positive implications for enhanced postoperative pain management. [ABSTRACT FROM AUTHOR]

Background. Although radical cystectomy (RC) is the clinical practice guideline-recommended treatment of muscle-invasive bladder cancer (MIBC), bladder-sparing trimodality therapy (TMT) has emerged as a valid treatment option. Findings comparing the survival outcomes for MIBC patients who underwent RC and TMT are inconclusive. Objective. We designed a large hospital-based multicohort study to compare the effectiveness of TMT with RC. Methods. Information on deaths was jointly retrieved from EMR (electronic medical record), cause of death registry, and chronic disease surveillance as well as study-specific questionnaire. To avoid the systematical difference between patients who received two modalities, RC-MIBC cohort was propensity score-matched to TMT-MIBC cohort, and the Cox proportional hazard regression was used to calculate the overall survival (OS) and disease-specific survival (DSS). Results. There were 891 MIBC patients treated with RC and another 891 MIBC patients who underwent with TMT in the propensity score matching. Comparable effectiveness between two modalities was observed for DSS (HR, 1.20; 95% confidence interval (CI), 0.94 to 1.49) and OS (HR, 1.17; 95% CI, 0.91 to 1.43) according to multiple adjustment after a median follow-up of approximately 9.3 years. However, a relatively higher mortality rate around 5 years after TMT treatment was found compared to RC (HR, 1.26; 95% CI, 1.01 to 1.53). The respective 5-year OS rates were 69% and 73% for TMT cohort and RC cohort, respectively. Conclusions. Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall. Treatment options should be suggested considering patients' age and willingness. [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence about hormone replacement therapy and colorectal carcinogenesis by demographic and clinical traits remains unclear. We aimed to assess this postulated association in a large multicentre study and further explore the modification effect by BMI and others. Methods: We retrospectively collected records of women diagnosed with colorectal cancer (CRC) at the age of 50 years and older during 2014–2017 and their HRT dispensing prior to CRC diagnosis in three tertiary hospitals in China. CRC cases were matched with controls at a ratio of 1:3 using nearest neighbour propensity scores matching to better control for the remaining imbalance between groups, which generated a total of 824 cases with 2472 controls. Results: Our study confirmed the inversed association between colorectal cancer risk and hormone replacement therapy (OR, 0.62; 95% CI, 0.54–0.75), which was more prominent among women having multiple HRT dispenses (OR, 0.60; 95% CI, 0.52–0.76). Furthermore, significant associations were consistently observed for the short-term (OR, 0.69; 95% CI, 0.57–0.88), middle-term (OR, 0.51; 95% CI, 0.41–0.66), and long-term HRT users (OR, 0.70; 95% CI, 0.43–0.90). Estrogen-related regimen reduced CRC risk more than progestogen-only. We, for the first time, found that the modifying effect of BMI on HRT use and CRC risk was in different ways when BMI was categorized by a medium level of 27. Conclusion: Our findings mainly suggest that there might be a different mechanism for the reversed association between HRT and colorectal tumorigenesis by BMI level, providing thoughts on clinical treatment of CRC. [ABSTRACT FROM AUTHOR]

Muscle-invasive bladder urothelial carcinoma (MIBC) is a highly invasive cancer, which leads to prevalent recurrence and poor prognosis. Exploring the association of DNA methylation and the prognosis of MIBC will thus be of important value in clinical management and treatment. Bumphunter method and adaptive lasso regression were used to explore the relationship between different methylation regions (DMRs) and the prognosis of MIBC. Next, we constructed a risk prognosis model and validated this model. Moreover, the performance of this risk model was examined by using time-dependent receiver operating characteristic curve (ROC). We identified 58,449 different methylation sites and 490 different methylation regions. Among them, 11 DMRs were associated with the prognosis of MIBC through rigorous screening. Through the linear combination of 11 DMRs, a putative marker was developed, which can distinguish the survival risk in both the training dataset (HR = 2.58, 95% CI = (1.64, 4.05)) and the verification dataset (HR = 2.77, 95% CI = (1.25, 6.15)). Relatively high predictive values were observed from this model for training dataset (AUC = 0.791) and verification dataset (AUC = 0.668). Stratified analysis showed that the association was independent of gender. A nomogram was additionally generated to predict 5-year survival probability containing risk score and pathological stage. Its performance was evaluated by applying calibration curve. The methylation signature risk model based on 11 DMRs may be a reliable prognostic signature for MIBC, which provides new insights into development of individualized therapy for MIBC. [ABSTRACT FROM AUTHOR]

Aim: There is no consensus regarding the association between hormone replacement therapy (HRT) and risk of meningioma so far. We conducted the first study among Chinese female patients to investigate the influence of HRT use on the risk of meningioma. Methods: We retrospectively collected records of diagnosis of meningioma for women aged 50 years and above during 2011–2016 and dispense of HRT prior to meningioma diagnosis in three tertiary hospitals in China. Meningioma cases were matched with controls at a ratio of 1:2 by using nearest neighbor propensity scores matching in order to balance the baseline characteristics between groups, which generated a total of 629 cases with 1258 controls. Results: We observed prior use of HRT associated with increased risk of meningioma (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0–1.4) and the association was more prominent among women having multiple HRT dispenses and longer term exposure (OR, 1.3; 95% CI, 1.1–1.6), among those with combination therapy of estrogens and progestogens (OR, 1.3; 95% CI, 1.1–1.7) than monotherapy, and among progestogen users than estrogen users as for monotherapy. Furthermore, vaginal, subcutaneous implant seems to be associated with a higher risk of meningioma compared with oral administration although no significance had been reached. Conclusion: This case–control study provides evidence that hormone use for an HRT purpose might constitute the development and growth of meningioma as an independent risk factor, especially for combination therapy and/or long‐term users, which supports that meningioma might be a hormone‐sensitive tumor. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have made a significant breakthrough in the treatment of solid tumors; however, their use also generates unique immune-related adverse effects (irAEs). Here, we performed a systematic review and meta-analysis to assess the risk of immune-related liver dysfunction between in patients treated by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors exclusively and chemotherapy. Methods: A comprehensive search of multiple databases identified eligible studies, including randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors exclusively and chemotherapy in patients with different solid tumors was carried out. The elevations of alanine aminotransferase (ALT) and aspartic aminotransferase (AST) were used to evaluate liver dysfunction. The relative risk (RR) and 95% confidence intervals (CI) were calculated and analyzed by Review Manager 5.3 and STATA version 12.0 statistical software. Results: After screening and eligibility assessment, a total of 5638 patients from 12 RCTs were included in our meta-analysis. In comparison with chemotherapy, patients treated with PD-1/PD-L1 inhibitors exclusively showed an increased incidence of all-grade ALT/AST elevations (ALT: RR, 1.52, 95% CI, 1.09–2.13; p = 0.01; AST: RR, 1.96, 95% CI, 1.37–2.81; p = 0.0002). Patients receiving PD-1 inhibitors showed the significantly higher risk of all-grade ALT/AST elevations incidence than those receiving chemotherapy (ALT: RR, 1.47; 95% CI, 1.05–2.07; p = 0.03; AST: RR, 1.90, 95% CI, 1.32–2.73; p = 0.0005). However, no significant difference was found between PD-L1 inhibitor and chemotherapy group. Moreover, for non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC), patients treated with PD-1/PD-L1 inhibitors exclusively exhibited a significant higher risk of all-grade ALT elevation incidence (NSCLC: RR, 1.92; 95% CI, 1.23–3.02; p = 0.004; UC: RR, 3.36; 95% CI, 1.12–10.06, p = 0.03) and all-grade AST elevation incidence (NSCLC: RR, 2.37; 95% CI, 1.45–3.87, p = 0.0005; UC: RR, 4.47; 95% CI, 1.30–15.38, p = 0.02) than chemotherapy. Conclusions: The meta-analysis confirms that PD-1/PD-L1 inhibitors exclusive pose an increased risk of immune-related liver dysfunction than chemotherapy. PD-1/PD-L1 blockade in NSCLC and UC increase the risk of immune-related liver dysfunction, but not in melanoma (MM) and head-neck squamous cell carcinoma (HNSCC). [ABSTRACT FROM AUTHOR]

The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1* 6, UGT1A1* 28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m2 once every 3 weeks ( n = 45). Genotypic–phenotypic correlates showed a non-significant influence of UGT1A1* 28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 ( P > 0.05), as well as severity of neutropenia ( P > 0.05). Significantly higher exposure levels to SN-38 ( P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1* 6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC ≤ 500/µL) was 27% in patients homozygous for UGT1A1* 6 compared with the reference group. Furthermore, the presence of the UGT1A1* 6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1* 6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% ( n = 36) of the patient population in the present study. ( Cancer Sci 2007; 98: 1461–1467) [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the population frequency of SLCO1B1 polymorphic variants in three distinct healthy Asian populations, namely Chinese ( n = 100), Malay ( n = 100) and Indian ( n = 100), and to explore the association between haplotype-tagged single nucleotide polymorphisms (htSNPs) on hepatic SLCO1B1 mRNA expression. The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients. Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A ( P = 0.030)] as well as three coding region SNPs [c.388G>A ( P < 0.001); c.571T>C ( P < 0.001); c.597C>T ( P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP. Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations. [ABSTRACT FROM AUTHOR]

Keywords: cancer epidemiology; China; cancer incidence; cancer mortality; cancer survival; cohort Cancer epidemiology, China, cancer incidence, cancer mortality, cancer survival, cohort. [Extracted from the article]

A correction to the article "Pharmacogenetics of SLCO1B1: haplotypes, htSNPs and hepatic expression in three distinct Asian populations," that was published in the June 21, 2007 issue is presented.