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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]

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]

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]