BackgroundThe Healthy Eating Index (HEI-2020), a metric that assesses overall diet quality based on compliance with the 2020–2025 Dietary Guidelines for Americans, has been insufficiently investigated in relation to both colorectal cancer (CRC) incidence and mortality. To address this gap, we conducted a population-based prospective study of 101,709 U.S. adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, examining the associations between HEI-2020 adherence and risks of CRC incidence and death.MethodsA total of 101,709 participants were included in this study. Dietary information was collected using the Diet History Questionnaire (DHQ), and adherence to the HEI-2020 was assessed. Higher HEI-2020 scores indicated better adherence to a healthy diet. Cox proportional hazards regression analyses were performed to examine the association between HEI-2020 scores and CRC risk. To further explore the dose–response relationship between HEI-2020 scores and CRC incidence, a restricted cubic spline (RCS) model was applied. Subgroup analyses were conducted to identify potential modifiers that might interact with HEI-2020 in relation to CRC incidence, and sensitivity analyses were performed to assess the robustness of the established association.ResultThis study included 101,709 participants, with 1,100 incident CRC cases and 314 deaths. The fully adjusted model showed that participants in the highest HEI-2020 quartile had a lower point estimate for CRC incidence than those in the lowest quartile, although this comparison did not reach statistical significance (HR = 0.86; 95% CI: 0.73–1.02). A significant decreasing trend in CRC incidence risk was observed across HEI-2020 quartiles (P for trend = 0.021). Higher HEI-2020 scores were significantly associated with lower CRC-specific mortality (Q4 vs. Q1: HR = 0.61; 95% CI: 0.45–0.85; P for trend = 0.001), and this association remained consistent in competing-risk analyses. Site-specific analyses suggested lower risks for distal colon cancer and a borderline lower point estimate for rectal cancer, as well as a decreasing trend in proximal colon cancer mortality. Sensitivity and subgroup analyses confirmed the robustness of the findings.ConclusionThis study suggests that higher HEI-2020 scores, reflecting better alignment with the Dietary Guidelines for Americans, are associated with a significant decreasing trend in CRC incidence risk and a lower risk of CRC-specific mortality.

Background:As head and neck cancer (HNC) incidence rises, prevention demands attention to diet. Yet most studies emphasize total fat intake while overlooking fat quality. To address this gap, we examined the association between fat quality index (FQI) and HNC risk. Methods:A total of 98,560 participants were included in this study. Hazard ratios (HR) with 95% CIs for overall HNC were estimated using multivariable Cox models. Site-specific analyses were conducted, and fatty-acid components were evaluated. Effect modification was tested across prespecified subgroups. A joint analysis combined FQI tertiles with percent energy from fat. Robustness was assessed through multiple sensitivity analyses. Results:Over a median 8.8 years, 267 HNC cases occurred. Higher FQI significantly reduced overall HNC risk (fully adjusted HR for Quartile 4 vs. Quartile 1: 0.62; 95% CI, 0.42-0.91; P-trend = 0.011), demonstrating a linear inverse dose-response. Findings were consistent across subgroups and sensitivity analyses. By subsite, associations were strongest for laryngeal cancer (HR for Q4 vs. Q1: 0.43; 95% CI: 0.21-0.88). The joint analysis revealed that higher FQI was associated with lower HNC risk even among individuals with high total fat intake (HR = 0.36; 95% CI: 0.21-0.59), with no significant interaction observed. Higher Monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) intakes were inversely associated with HNC, whereas Saturated fatty acids (SFA) and Trans fatty acids (TFA) were not. Conclusion:Higher FQI is associated with lower HNC incidence, independent of total fat intake. These findings highlight that prioritizing dietary fat quality over quantity may be a critical strategy for HNC primary prevention.

Background:No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods:Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust. Results:During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22% lower incidence (HR Q4 vs. Q1: 0.78; 95% CI: 0.65-0.93; p = 0.006 for trend) and 38% lower mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.44-0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36% reduction; HR: 0.64; 95% CI: 0.43-0.96; p = 0.010 for trend) and mortality (56% reduction; HR: 0.44; 95% CI: 0.19-1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34%; HR: 0.66; 95% CI: 0.44-1.00; p = 0.031 for trend). Conclusion:Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.

Background:The impact of protein quality on lung cancer risk in the U.S. population remains unclear. We conducted a large-scale prospective cohort study with 101,755 American adults enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (1993-2001). Methods:The Healthy Plate Protein Quality Index (HPPQI) was used to assess dietary protein quality. Cox proportional hazards regression was applied to analyze the relationships between HPPQI and lung cancer incidence and mortality. Subgroup and sensitivity analyses were conducted. Results:Over a mean follow-up of 8.82 ± 1.95 years (897,809 person-years; median 9.40 years), 1,706 lung cancer cases (1,464 NSCLC and 242 SCLC) and 1,217 related deaths (1,005 NSCLC and 212 SCLC) were recorded. Higher HPPQI was significantly linked to lower lung cancer incidence (HR Q4 vs. Q1: 0.63; 95% CI: 0.55-0.73; P < 0.001 for trend) and mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.52-0.74; P < 0.001 for trend), consistent in both NSCLC and SCLC. Sensitivity analysis confirmed the study's robustness across various participant characteristics. Conclusions:Adherence to a dietary pattern characterized by a higher HPPQI is associated with reduced lung cancer risk.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and has become a recognized global health problem. Therefore, the search for new anti-CRC agents or the exploration of new effective drug targets for CRC therapy is urgent. Chloroquine (CQ) is a widely-used antimalarial drug and has shown anti-proliferative effects in CRC. However, the underlying mechanisms are not well understood, particularly as the direct targets of CQ have not been identified. In this study, choline kinase alpha (CHKA) and ATP-dependent 6-phosphofructokinase, muscle type (PFKM) were identified and verified as the binding targets of CQ. CQ specifically binds to CHKA, inhibits its expression and enzymatic activity, and downregulates the downstream phosphorylation of PI3K and AKT, thereby suppressing tumor cell proliferation and inducing apoptosis. CQ also binds to PFKM and inhibits its expression and activity, thereby blocking the Warburg effect. In addition, the downregulation of CHKA can decrease the expression of PFKM and inhibit its activity, thereby blocking the Warburg effect. These observations shed new light on the antitumor mechanisms of CQ and provide new evidence for the close relationship between the PI3K/AKT signaling pathway and the Warburg effect, providing new therapeutic targets for treating CRC.

This study aimed to evaluate the safety and efficacy of intestinal stent placement as a bridge to surgery in patients with left colon cancer complicated by intestinal obstruction (LCCO). A retrospective cohort analysis was conducted on 111 patients diagnosed with LCCO at The Second Affiliated Hospital of Chongqing Medical University between January 2015 and August 2019. Patients were divided into two groups: the stent group (SG, n = 41) and the emergency surgery group (EG, n = 70). Primary endpoints included 3-year progression-free survival (PFS), local recurrence, and distant metastasis rates. Secondary endpoints encompassed 3-year overall survival (OS), intraoperative parameters (lymph node dissection, blood loss, operative time), enterostomy rate, postoperative complications, and hospital stay duration. No significant differences were observed between SG and EG in 3-year PFS (59

10537 Background: Achieving robust early-stage sensitivity in multi-cancer early detection (MCED) poses challenges, relying on large cohorts of early-stage samples and reliable prediction frameworks. Particularly for gastrointestinal cancers (GICs) with poor compliance of screening, early-stage sensitivity in MCED remains insufficient. Moreover, accurate tumor localization is crucial for choosing subsequent diagnostic procedures but remains suboptimal. We evaluate the performance of Genie-seq within the ProFuture study (NCT05874648), focusing on its capacity to detect five high-mortality cancers: lung, colorectal, liver, stomach, and esophageal cancers. Methods: The ProFuture study is a prospective multicenter case-control study that initially enrolled 3,515 participants. Following evaluations and a minimum of a half-year follow-up, 3,036 participants remained analyzable. Participants were divided into training (920 cancer; 629 non-cancer), validation (300 cancer; 215 non-cancer), and independent validation (605 cancer; 367 non-cancer) sets. Plasma cfDNA underwent a 1000X target enzymatic methyl sequencing assay (Genie-seq) targeting cancer-specific methylation patterns identified from 2,420 tumor and plasma samples. The assay normalizes abnormal fragment reads within blocks to minimize interference, using a maximization model to select sensitive and robust features. A gradient-boosted tree model was developed to integrate these features for cancer prediction, utilizing a one-vs-rest strategy to determine the tissue-of-origin (TOO). Results: Specificity remained consistently high across all phases: 99.0% (95% CI: 97.7-99.6%) in training, 99.1% (96.7-99.9%) in validation, and 99.2% (97.6-99.8%) in independent validation. Sensitivity was 68.6% (65.5-71.6%) in training, 71.0% (65.5-76.1%) in validation and 69.6% (65.8-73.2%) in independent validation. In independent validation set, stages I-III (account for 85.5% of cases) sensitivity reached 65.8% (61.5-69.9%) for all cancer types and 72.1% (66.9-76.9%) for three GICs. The TOO classifier assigned the origin in all screen-positive cases, achieving an accuracy of 87.4% (83.9-90.4%) in independent validation, including reducing misclassification from lung to esophageal cancer due to squamous similarity to 4.5%. Conclusions: This MCED test accurately identified signals from five tumor types especially in the early stages. Precise TOO localization minimizes the healthcare burden of subsequent diagnoses. The consistency of performance from training to clinical validation underscores the robustness of feature selection strategy, mitigating the risk of overfitting. Notably, this study demonstrated exceptional sensitive detection of early-stage GICs, indicating the potential efficacy of Genie-seq in MCED within the ongoing interventional Prosight study (NCT06790355). Clinical trial information: NCT05874648 .

BACKGROUND:The association between the Dietary Inflammatory Index (DII) and lung cancer incidence remains unclear. This inconsistency may be attributed to not considering total energy intake and dietary supplement use adequately. To provide reliable evidence, we conducted a secondary analysis of data from the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to examine the association between lung cancer incidence and E-DII (Energy-adjusted DII) derived from both food and supplements as well as from food only. METHODS:The data of participants were retrieved from the PLCO Cancer Screening Trial. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of lung cancer and its subtypes, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Additionally, Restricted Cubic Spline (RCS) were used to describe the linear dose-response relationship between lung cancer and its subtypes across the entire EDII score range, subgroup analyses were conducted to identify potential modifiers, and sensitivity analyses were performed to strengthen the stability of our results. RESULTS:Over a median follow-up duration of 9.40 years, totally 1,706 incident cases of lung cancer were identified. Our analyses demonstrated that both higher E-DII from food and supplements (HR Q4 vs. Q1: 1.31, 95%CI: 1.14, 1.52, Ptrend = 0.002) and E-DII from food only (HR Q4 vs. Q1: 1.39, 95%CI: 1.22, 1.58, Ptrend <0.001) were associated with an elevated lung cancer incidence. RCS revealed a linear dose-response relationship between both overall lung cancer incidence (Pnonlinearity = 0.509) and NSCLC incidence (Pnonlinearity = 0.489) and E-DII from food and supplements. However, a significant inverse U-shaped association between E-DII from food and supplements SCLC was exhibited (Pnonlinearity = 0.016). The results of the subgroup analyses showed that smoking quantity reveals significant interactions between lung cancer and E-DII from food only (Pinteraction = 0.039). Finally, sensitivity analyses reinforced the robustness of our findings. CONCLUSION:Our findings revealed a positive association between E-DII and lung cancer incidence among U.S. adults aged 55 years and older, particular in populations with higher smoking exposure, which suggesting dietary inflammatory potential may represent an important modifiable risk factor for lung cancer prevention. Furthermore, our analyses demonstrated that SCLC and NSCLC exhibit distinct inflammatory response patterns, indicating potential differences in their biological mechanisms.

Although neoadjuvant immunotherapy showed promising efficacy in locally advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) colon cancer, whether dual immune checkpoint inhibition provides additional benefit over anti-PD-1 monotherapy remains unclear. This randomized phase 1b trial (NCT05890742) evaluated a neoadjuvant regimen of IBI310 (anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) plus sintilimab (n = 52) versus sintilimab monotherapy (n = 49). Surgery was performed in 51 and 45 patients, respectively. The primary endpoint, pathological complete response (pCR) rate, was significantly higher in the combination compared to the monotherapy arm within the modified intent-to-treat (mITT) population (78.4% versus 46.7%, p = 0.0015), with consistent results in the intent-to-treat (ITT) population (76.9% versus 42.9%). Safety in both arms was comparable and manageable without new safety signals. After a median follow-up of 21.4 months, no disease recurrences occurred. One death occurred in each arm due to postoperative complication and adverse events. These findings demonstrate the added benefit of neoadjuvant IBI310 plus sintilimab over sintilimab monotherapy for locally advanced MSI-H/dMMR colon cancer.

Objective:Given the significantly increased risk of colorectal adenoma in middle-aged and elderly populations, identifying modifiable risk factors remains a priority. While dietary protein is an essential nutrient in human metabolism, its relationship with colorectal adenoma remains controversial. With advances in nutritional science, contemporary dietary guidelines advocate increasing plant-based protein intake to achieve a more balanced protein consumption pattern. To provide new insights, we sought to investigate the association between colorectal adenoma risk and the Protein Diet Score, which comprehensively evaluates both protein intake and sources. Methods:This analysis was based on data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline was employed to illustrate the variation in colorectal adenoma risk across the entire spectrum of the Protein Diet Score. Additionally, subgroup analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings. Results:During the mean follow-up period of 11.0 years, 992 newly diagnosed colorectal adenomas were identified. In the fully adjustment for potential confounders, the inverse association between Protein Diet Score and colorectal adenoma risk remained statistically significant with an HR of 0.81 (95% CI: 0.67-0.99; Ptrend =0.005) comparing the highest versus lowest quartile. Restricted cubic spline analysis revealed a linear inverse relationship between Protein Diet Score and colorectal adenoma risk (P for nonlinearity =0.317). In the subgroup analyses, we observed a more pronounced inverse association between Protein Diet Score and colorectal adenoma among participants with a history of hypertension (HR Quartile 4 vs. Quartile 1: 0.60; 95% CI: 0.43-0.85; Pinteraction =0.017). Finally, a series of sensitivity analyses strengthened the robustness of our findings. Conclusion:Our findings indicate that higher Protein Diet Score is associated with reduced colorectal adenoma incidence among middle-aged and elderly Americans, with similar findings observed for the PAR. These results provide important evidence for optimizing protein intake and source composition to promote intestinal health.

4133 Background: In China, the 5-year survival rate of liver cancer patients is only 14%, far lower than the average of 43.7% for all cancer types. Early diagnosis and treatment are essential for survival. Traditional screening methods like AFP combined with abdominal ultrasound have low sensitivity. Recent studies suggest that blood cell-free DNA (cfDNA) characteristics could be a new screening approach for liver cancer. This study aims to compare methylation and fragmentation signals among liver cancer, hepatitis, cirrhosis patients, and healthy individuals, innovatively using these signals to construct an early-detection model which could improve patient prognosis. Methods: From July 2023 to November 2024, 315 blood samples were prospectively collected from five Chinese hospitals. The sample set included 105 liver cancer patients and 210 non-liver cancer controls (33 hepatitis, 30 cirrhosis, 147 healthy). This multi-center, multi-disease-controlled collection provides a robust data basis. Targeted enzymatic methyl sequencing detected over 600,000 methylation sites, enabling precise exploration of liver-cancer-related methylation. Beyond methylation, novel fragmentation features like break-point motifs, end motifs, arm-level count, fragment-size distribution and ratio were obtained. These, combined with methylation data, offer a multi-dimensional view for studying liver cancer pathogenesis and biomarkers. A gradient-boosted tree model, integrating 3840 methylation DMR features and fragmentomic model-predicted probabilities, was built. A nested cross-validation framework was used to optimize the model and ensure result accuracy. Results: The model achieved a high AUC of 0.97(95%CI:0.95-0.99) in liver cancer detection. At 96.2% specificity, the model had a 91.4% sensitivity for overall liver cancer detection, with 83.7% and 95.8% sensitivity for stage I and II respectively. Among 63 patients with hepatitis or cirrhosis, the model accurately predicted negative results in 88.9% of patients. Notably, for patients hard to identify by traditional tumor markers like AFP and DCP, the model showed high detection rates. When AFP < 400 ng/ml, the detection rate was 88.9%, and with concurrent DCP < 40 ng/ml, it reached 87.0%. When AFP < 20 ng/ml, the detection rate was 89.5%, and with DCP < 40 ng/ml simultaneously, the detection rate was 83.3%. Conclusions: This study established an early-detection model for liver cancer by leveraging cfDNA methylation and fragmentation signals. The model demonstrated remarkable performance, particularly in detecting liver cancer patients who are difficult to identify through conventional methods. It blazes a new trail for the early detection of liver cancer and could significantly enhance patient prognosis.

Background:Protein quantity's link to colorectal cancer (CRC) risk is known, but protein quality's impact on US populations remains unclear. This study fills the gap via a population - based prospective study of 101,709 American adults from the PLCO Cancer Screening Trial. Methods:From 154,887 adults aged 55-74 years at 10 US screening centers, we formed the study group. HPPQI was calculated from the DHQ. Cox regression analysis determined HRs and 95% CIs for HPPQI - CRC associations. Subgroup and sensitivity analyses identified modifiers and ensured robustness. Results:During the study period, 1100 CRC cases and 314 CRC-related deaths were documented. In our result, HPPQI was significantly negatively associated with incidence of CRC (HR Q4 vs. Q1: 0.77; 95% CI: 0.65, 0.93; P = 0.009 for trend), as well as mortality rate (HR Q4 vs. Q1: 0.66; 95% CI: 0.47, 0.91; P = 0.024 for trend). The relationships between HPPQI and the incidence and mortality of CRC were robustly supported by sensitivity analyses. Nevertheless, upon separate examination of the relationships between HPPQI and proximal colon cancer, distal colon cancer, and rectal cancer, none of these associations attained statistical significance (all P-values > 0.05). Conclusion:Our findings suggest focusing on higher quality of protein consumption may be an effective approach to reduce the risk of CRC in the US population.

[This corrects the article DOI: 10.3389/fimmu.2025.1529011.].

4136 Background: Aberrant methylation patterns in cell-free DNA (cfDNA) have been identified as effective biomarkers for HCC early detection, with circulating tumor DNA (ctDNA) from HCC patients exhibiting distinct methylation signatures. Additionally, HBV infection and the associated methylation alterations are closely linked to the development and progression of both cirrhosis and HCC. In this study, we utilize an ultra-sensitive Methylation Anchor Probe for Low Signal Enrichment (MAPLE) to enrich HCC-related methylation signals in ctDNA, as well as those from HBV genomes. By integrating these signals with a machine learning model, we achieve improved discrimination between HCC patients and non-cancer controls, while reducing false positives in individuals with cirrhosis. Methods: Whole blood samples were collected from 246 participants, including 96 HCC patients, 123 healthy controls, and 27 cirrhosis individuals. cfDNA was extracted from plasma, followed by enzymatic conversion and library preparation. Targeted hybrid capture was performed using a custom-designed panel that enriched methylation signals associated with HCC and HBV CpG islands. The final libraries were sequenced using next-generation sequencing (NGS). A machine learning model was developed, incorporating methylation features derived from both the human genomic regions and HBV CpG islands. Participants were randomly divided into training and test sets at a 3:1 ratio, with the training set undergoing 5-fold cross-validation for model optimization. To assess model robustness, 40 resampling iterations were conducted to evaluate performance in distinguishing HCC patients across various stages from non-cancer individuals. Results: Among all participants, 39.8% tested positive for HBV. Incorporating methylation features from the HBV genome into the model improved sensitivity for detecting early-stage HCC in HBV-positive individuals and enhanced accuracy in distinguishing early-stage HCC from cirrhosis. Analysis of selected HBV methylation features revealed hypermethylation in HCC patients compared to individuals with cirrhosis and healthy controls. The final machine learning model achieved a specificity of 97.6% (96.2%–97.9%). Sensitivities for detecting HCC across all stages were: I: 76.4% (73.5%–79.4%), II: 94.6% (92.0%–97.3%), III: 99.5% (98.8%–100.0%), and IV: 100.0% (100.0%–100.0%). For distinguishing cirrhosis, the model demonstrated a specificity of 81.9% (77.6%–86.3%). Conclusions: Using the ultra-sensitive MAPLE technique, we developed a novel panel that enriches methylation signals from both the human and HBV genomes. This assay significantly improved sensitivity for detecting early-stage HCC. By incorporating HBV genome features, we further enhanced the accuracy of distinguishing early-stage HCC from cirrhosis in HBV-positive individuals.

OBJECTIVES:The EAT-Lancet diet (ELD) has shown potential in reducing obesity and type 2 diabetes, both of which are closely associated with the development of renal cancer. However, the specific relationship between this dietary pattern and renal cancer remains largely unexplored. This study aims to address this gap in knowledge by investigating the association between ELD adherence and renal cancer risk. STUDY DESIGN:A population-based prospective study of 101,755 American adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. METHODS:Cox proportional hazards models were utilized to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between ELD adherence and renal cancer risk, adjusting for potential confounders. Restricted cubic spline plots visualized the dose-response relationship. Subgroup analyses evaluated potential effect modifiers, and sensitivity analyses assessed the robustness of findings. RESULTS:Over 899,337.5 person-years of follow-up, 446 cases of renal cancer were identified. In the fully adjusted model, a significant inverse association was observed between higher ELD adherence and renal cancer risk (HR for highest vs. lowest quartile: 0.65; 95 % CI: 0.49-0.88; P for trend = 0.002). A restricted cubic spline plot revealed a nonlinear, inverse dose-response relationship (P for nonlinearity = 0.046). Subgroup analyses showed consistent findings across participant characteristics. Sensitivity analyses further reinforced the robustness of the primary association. CONCLUSIONS:In this large prospective study, adherence to the EAT-Lancet diet was inversely associated with the risk of developing renal cancer, suggesting the potential benefits of this dietary pattern in mitigating renal cancer burden.

Objectives: To explore the relationships between dietary potential acid load and renal cancer (RC) incidence and mortality. Study design: A prospective cohort study involving 97,166 U S. adults aged 55-74 years. Methods: Data utilized in this study were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Dietary potential acid load was assessed by dietary acid load (DAL), potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores using a validated Diet History Questionnaire (DHQ). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for RC incidence and mortality with adjustment for potential confounders. Restricted cubic spline (RCS) plots were utilized to reveal whether there were nonlinear associations between the DAL, PRAL, and NEAP scores and RC incidence and mortality. Results: During a follow-up period of 859,907 and 1,467,573 person-years, 423 RC cases and 221 mortality cases were documented. DAL, PRAL, and NEAP scores were positively associated with RC incidence (DAL: HR 1.41; 95% CI 1.05, 1.90; P-trend = 0.010; PRAL: HR 1.45; 95% CI 1.10, 1.91; P-trend = 0.010; NEAP: HR 1.39; 95% CI 1.04, 1.85; P-trend = 0.029). Similar associations were observed between DAL, PRAL, and NEAP scores and RC mortality. The RCS plots demonstrated a nonlinear association between DAL score and RC risk, while a linear association was observed between DAL score and RC mortality. Similar linear associations were found between PRAL and NEAP scores and RC incidence and mortality. Conclusion: A higher dietary potential acid load was associated with higher risk of RC incidence and mortality in American adults.

AbstractBackground: Previous studies have suggested anthocyanidins or anthocyanidin-rich foods and extracts exhibit protective effects against various cancers. However, the relationship between dietary anthocyanidins and the risk of biliary cancer remains uncertain. Methods: This study used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate the relationship between total anthocyanidins intake and biliary cancer incidence. Cox regression analysis was conducted to estimate HRs and corresponding 95% confidence intervals (CI) for the incidence of biliary cancer, with adjustments made for confounding factors. A restricted cubic spline model was employed to examine the dose–response relationship. In addition, subgroup and sensitivity analyses were conducted to evaluate potential interactions and test the model's robustness. Results: During 8.9 years and 872,645.3 person-years of follow-up, 95 cases of biliary cancer were observed. The incidence rate of biliary cancer in this study was 11 cases per 100,000 person-years. Using the fully adjusted Cox regression model, the inverse association was observed between total anthocyanidins intake and the risk of biliary cancer (HR Q4 vs..Q1: 0.52; 95% CI: 0.29–0.91; Ptrend = 0.043). This association remained significant in sensitivity analyses. A linear dose–response relationship (Pnonlinearity = 0.118) and potential interaction with drinking status (Pinteraction = 0.033) were identified. Conclusions: This study provides evidence of an inverse association between total anthocyanidins intake and biliary cancer incidence. Impact: Our study found a total anthocyanidin-rich diet was associated with a reduced risk of biliary cancer in Americans ages 55 to 74 years.

Supplementary Table 2. Association of Standardized total anthocyanidins with the risk of biliary cancer.

Supplementary Table 3. Association between subclasses anthocyanidins and biliary cancer risk.

ObjectivesThere is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older.DesignA prospective cohort study with a mean follow-up time of 8.8 years.Setting and participantsThis study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer.MethodsDietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings.ResultsDuring a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66−0.89), NSCLC (HR, 0.79; 95% CI, 0.67−0.93), and SCLC (HR, 0.59; 95% CI, 0.38−0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60−0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10–1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20–3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes.ConclusionsOur findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.