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BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.
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BACKGROUND: Ovarian cancer is a frequently-occurring reproductive system malignancy in females, which leads to an annual of over 100 thousand deaths worldwide. METHODS: The electronic databases, including GEPIA, ONCOMINE, Metascape, and Kaplan-Meier Plotter, were used to examine both survival and transcriptional data regarding the cell division cycle associated (CDCA) gene family among ovarian cancer patients. RESULTS: All CDCA genes expression levels were up-regulated in ovarian cancer tissues relative to those in non-carcinoma ovarian counterparts. Besides, CDCA5/7 expression levels were related to the late tumor stage. In addition, the Kaplan-Meier Plotter database was employed to carry out survival analysis, which suggested that ovarian cancer patients with increased CDCA2/3/5/7 expression levels had poor overall survival (OS) (P<0.05). Moreover, ovarian cancer patients that had up-regulated mRNA expression levels of CDCA2/5/8 had markedly reduced progression-free survival (PFS) (P<0.05); and up-regulated CDCA4 expression showed remarkable association with reduced post-progression survival (PPS) (P<0.05). Additionally, the following processes were affected by CDCA genes alterations, including R-HAS-2500257: resolution of sister chromatid cohesion; GO:0051301: cell division; CORUM: 1118: Chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression, all of which were subjected to marked regulation since the alterations affected CDCA genes. CONCLUSIONS: Up-regulated CDCA gene expression in ovarian cancer tissues probably played a crucial part in the occurrence of ovarian cancer. The up-regulated CDCA2/3/5/7 expression levels were used as the potential prognostic markers to improve the poor ovarian cancer survival and prognostic accuracy. Moreover, CDCA genes probably exerted their functions in tumorigenesis through the PLK1 pathway.
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Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Here, we analyzed the impact of local and systemic environments on the tumor response to preoperative chemoradiotherapy in rectal cancer. We recruited 141 patients with rectal cancer treated with nCRT. We evaluated the local tumor environment, including tumor-infiltrating lymphocytes (TILs), intratumor budding (ITB), and the systemic inflammatory environment, including the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) level. Our finding revealed that tumor regression was significantly associated with the density of CD8+ TILs in the intraepithelial, the presence of ITB, the combination of NLR and CRP (NLR-CRP) value, and the combination of CD8+ intraepithelial TIL (iTIL) density and ITB presence. Moreover, multivariate analysis showed that only the combination of CD8+ iTILs and ITB was an independent predictive factor for the pathological response to nCRT in rectal cancer. Our finding demonstrate that the local tumor environment was a better predictor of the tumor response than the systemic environment and thus provided new insight into screening for patients who are more likely to benefit from cancer treatment.