Background. Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor‐infiltrating immune cells in BC are not fully understood. Methods. Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan‐Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor‐infiltrating immune cell fractions. Results. We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation‐enriched signaling pathways were related to immune‐associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. Conclusion. RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

Background: A number of studies have attempted to determine the prognostic significance of proliferating cell nuclear antigen (PCNA) in patients with colorectal cancer (CRC), but the reports are controversial and inconsistent. Thus, we conducted a meta-analysis to clarify the value of PCNA in CRC prognosis. Methods: A systematic search of relevant studies was performed in 4 electronic databases including PubMed, Cochrane Library, Embase, and Web of Science until February 2018. Hazard ratios (HRs) combined with 95% confidence intervals (95% CIs) were used to evaluate the relationship of PCNA expression with overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results: A total of 1372 CRC patients in 14 studies were identified eventually in our meta-analysis. The pooled HRs demonstrated that CRC patients with high PCNA expression was significantly correlated with poor OS (HR = 1.81; 95% CI: 1.51–2.17; P = .000), CSS (HR = 1.99; 95% CI: 1.04–3.79; P = .037); but not significantly with DFS (HR = 2.48; 95% CI: 0.98–6.26; P = .055). Sensitivity analysis showed the pooled HRs for OS, CSS, and DFS were stable when the included studies were removed one by one. Conclusion: Our meta-analysis suggested that high PCNA expression was associated with poor prognosis, and it could serve as a reliable and prognostic biomarker in CRC patients. More large-scale studies are needed to further support the conclusion.

Previous research has shown that adhering to the Eat‐Lancet diet (ELD) is associated with a lower risk of chronic diseases and mortality. However, the associations between ELD and lung cancer incidence and mortality are unclear. To address this gap, we conducted a prospective cohort study involving 101,755 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial in the USA. The ELD score was utilized to assess compliance with the ELD, with higher scores indicating greater compliance. We employed Cox regression analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ELD score with the incidence and mortality of lung cancer and its subtypes. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In total, 1706 cases of lung cancer and 1217 lung cancer‐associated deaths were recorded during the study period. Our analysis revealed that higher ELD scores were significantly associated with a reduced incidence (HR_{Quartile 4} vs. _{Quartile 1}: 0.73; 95% CI: 0.60, 0.89; p_trend = 0.001) and mortality (HR_{Quartile 4 vs. Quartile 1}: 0.74; 95% CI: 0.59, 0.93; p_trend = 0.005) of lung cancer in a dose–response manner (all p_nonlinearity > 0.05). The reliability of these results was supported by sensitivity analyses. Notably, these associations were primarily observed in non–small‐cell lung cancer. In conclusion, our findings suggest that adherence to the ELD may be associated with a reduced risk of lung cancer incidence and mortality.

Background: Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. Methods: We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. Results: During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67–0.96, P_trend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44–0.86, P_trend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. Conclusions: Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Background: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population.Methods: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses.Results: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HR_{Q4 vs. Q1}: 0.71; 95% CI = 0.54, 0.94;P_trend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose–response association between renal cancer risk with DRRD score was observed (P_nonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (P_interaction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (allP_trend < 0.05).Conclusions: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Background: The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined.Methods: A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers.Results: During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61–0.95,P_trend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55–0.97,P_trend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51–0.81,P_trend < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46–0.83,P_trend = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48–0.98,P_trend = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53–0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68–1.67) (P_interaction = 0.02).Conclusions: Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk.