Deciphering the folate puzzle: Unraveling the impact of genetic variations and metabolites on cancer risk.

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.

Relationship between educational level and survival of patients with cancer: A multicentre cohort study.

BACKGROUND: Although socioeconomic factors are important determinants of population mortality, the effect of educational level on the survival of patients with cancer in China is unclear. This study aimed to assess whether educational level is associated with the prognosis of patients with cancer and to explore the mediators of this association. METHODS: This multicentre cohort study included 18,251 patients diagnosed with cancer between May 2013 and December 2018. The main parameters measured were overall survival (OS) and all-cause mortality. The relationship between educational level and all-cause mortality was assessed using multifactor-corrected Cox survival analysis. Logistic regression was used to analyze the association between educational level and patient-generated subjective global assessment (PG-SGA). RESULTS: The mean age of the 18,251 participants (men, 9939 [54.4%]) was 57.37 ± 11.66 years. Multifactorial survival analysis showed that patients survived longer with increasing education (university and above vs. elementary school and below; p = p = <0.001, HR = 0.84, 95% CI: 0.77-0.92), and the differences were statistically significant in different subgroups. The potential impact factors included sex, age, TNM stage, and PG-SGA score. Logistic regression showed a significant negative association between educational level and the modifiable factor PG-SGA (secondary vs. primary and below; p = 0.004, HR = 0.90, 95% CI: 0.83-0.97; university and above vs. primary and below; p < 0.001, HR = 0.79, 95% CI: 0.71-0.88). CONCLUSIONS: Educational level was a significant prognostic factor for patients with cancer, independent of other known prognostic factors. This association was further improved by modifying the nutritional status.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

OBJECTIVES: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity. METHODS: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m2. The hazard ratio (HR) for death was calculated using Cox regression analysis. RESULTS: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013). CONCLUSION: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

The association of metabolic syndrome scores trajectory patterns with risk of all cancer types.

BACKGROUND: Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. METHODS: The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. RESULTS: Four MetS score trajectory patterns were identified: low-stable (n = 4657), moderate-low (n = 18,018), moderate-high (n = 18,288), and elevated-increasing (n = 3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR, 1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3 mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. CONCLUSIONS: Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. PLAIN LANGUAGE SUMMARY: The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.

Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study.

BACKGROUND: Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. METHODS: This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan-Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). RESULTS: C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28-1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19-1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25-1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels. CONCLUSION: Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.

Geriatric Nutritional Risk Index Combined with Calf Circumference Can be a Good Predictor of Prognosis in Patients Undergoing Surgery for Gastric or Colorectal Cancer.

OBJECTIVES: To explore the effect of combined hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancer and to screen for the best prognostic indicators. INTRODUCTION: Gastric and colorectal cancer is a widespread health concern worldwide and one of the major contributors to cancer-related death. The hematological and physical measurement indicators have been shown to associate with the prognosis of patients undergoing surgery for gastric or colorectal cancer, respectively, but it is still unclear whether the combination of the two can reflect the prognosis more effectively. METHODS: Thirteen hematological indicators and 5 physical measurement indicators were selected in this study, and the most promising ones were screened using LASSO regression. Then, the best prognostic indicators were selected by time-ROC curves. Survival curves were constructed using the Kaplan-Meier method, and the effects of hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancers were evaluated by Cox proportional risk regression analysis. In addition, the relationship between hematological and physical measurement indicators on secondary outcomes, including length of stay, hospitalization costs, intensive care unit (ICU) admission, and patients' subjective global assessment scores (PGSGA), was explored. RESULTS: After initial screening, among the hematological indicators, the geriatric nutritional risk index (GNRI) showed the highest mean area under the curve (AUC) values. Among body measures, calf circumference (CC) showed the highest mean AUC value. Further analyses showed that the combination of combined nutritional prognostic index (GNRI) and calf circumference (CC) (GNRI-CC) had the best performance in predicting the prognosis of patients undergoing surgery for gastric or colorectal cancers. Low GNRI, low CC, and low GNRI-low CC increased the risk of death by 44%, 48%, and 104%, respectively. Sensitivity analyses showed the same trend. In addition, low GNRI-low CC increased the risk of malnutrition by 17%. CONCLUSION: This study emphasizes that a combination of blood measures and body measures is essential to accurately assess the prognosis of patients undergoing surgery for gastric or colorectal cancers. The GNRI-CC is a good prognostic indicator and can also assess the risk of possible malnutrition.

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Association between a novel nutrition-inflammation prognostic grading system and overall survival in hospitalized adults with cancer: A retrospective cohort study.

BACKGROUND: Malnutrition and increased systemic inflammatory responses are highly prevalent in patients with cancer and they have a negative effect on prognosis. We aimed to develop a nutrition-inflammation prognostic grading system (NIPGS) for patients with cancer, which incorporates the Nutritional Risk Screening 2002 (NRS 2002) and C-reactive protein (CRP) levels. METHODS: This multicenter retrospective cohort study totally included 6891 patients diagnosed with cancer. A 4 × 4 matrix incorporating the four NRS 2002 categories within each of the four CRP categories was constructed. Groups with approximate hazard ratios (HRs) were clustered into one grade. The NIPGS consists of four grades, with the survival rate gradually decreasing from Grades 1 to 4. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. RESULTS: During a median follow-up of 18.70 months, 2818 death cases occurred. Kaplan-Meier curve showed the survival rate decreased from Grades 1 to 4 of NIPGS (P < 0.001). The NIPGS was an independent risk factor associated with OS adjusting for confounders, with HRs increasing from 1.22 (95% confidence interval [CI], 1.09-1.36; P < 0.001) in Grade 2, 1.58 (95% CI, 1.39-1.80; P < 0.001) in Grade 3 to 1.92 (95% CI, 1.73-2.13; P < 0.001) in Grade 4. A high NIPGS grade was also associated with an increased risk of short-term mortality, poor quality of life, and longer hospital stay and expenses. Two internal validation cohorts confirmed the results of our study. CONCLUSION: The NIPGS could be an effective prognostic tool for patients with cancer.

Modified Controlling Nutritional Status (mCONUT) serves as a promising prognostic factor in patients with cancer cachexia.

BACKGROUND: Malnutrition and systemic inflammation are considered 2 hallmarks of cancer cachexia. Our study aimed to construct a modified Controlling Nutritional Status by introducing C-reactive protein as an inflammatory parameter and investigate its prognostic value in patients with cancer cachexia. METHODS: This multicenter cohort study included 5221 patients with cancer, among whom 1719 were diagnosed with cachexia. Concordance index and receiver operating characteristic curves were used to compare prognostic values between the 2 systems. The primary outcome was overall survival, and comprehensive survival analyses were performed. The secondary outcomes were short-term survival, malnutrition, and quality of life. RESULTS: During the median follow-up of 17.47 mo, 813 deaths were recorded. The modified Controlling Nutritional Status was more accurate than Controlling Nutritional Status in predicting survival in patients with cancer cachexia. Patients in the high Controlling Nutritional Status/modified Controlling Nutritional Status group had a significantly shorter overall survival. Multivariate Cox analysis confirmed high Controlling Nutritional Status (hazard ratio = 1.34, 95% CI, 1.13-1.58; P < 0.001) and modified Controlling Nutritional Status (hazard ratio = 1.46; 95% CI, 1.26-1.69; P < 0.001) were independent risk factors for survival, adjusting for confounders. In subgroup analyses, a high modified Controlling Nutritional Status score had a significantly negative effect on survival in cachexia patients with upper gastrointestinal and colorectal cancer, especially for advanced-stage (stages III and IV) patients. The risk of short-term mortality and experiencing malnutrition rose to 1.48 and 1.13 times, respectively, in the high modified Controlling Nutritional Status group, as well as that for poorer life quality. CONCLUSION: The modified Controlling Nutritional Status group comprehensively reflects nutritional, immune, and inflammatory status and serves as a powerful prognostic scoring system in patients with cancer cachexia.

The age-related obesity paradigm: results from two large prospective cohort studies.

BACKGROUND: The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival. METHODS: The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil-to-lymphocyte ratio (NLR) > 3. Model-based causal mediation analysis was used to identify the mediators. RESULTS: A total of 52 270 (weighted population: 528506229) participants of the NHANES [mean follow-up times: 10.2 years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC [mean follow-up times: 2.9 years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged-related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%). CONCLUSIONS: The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all-cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.

Discovery of distinct cancer cachexia phenotypes using an unsupervised machine-learning algorithm.

OBJECTIVES: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort. METHODS: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality. RESULTS: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results. CONCLUSIONS: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials.

Poor sleep quality association with higher lung cancer risk: a nested case-control study.

Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

Prognostic value of insulin resistance in patients with female reproductive system malignancies: A multicenter cohort study.

BACKGROUND: Insulin resistance (IR) and systemic inflammation are common in patients with cancer and are associated with poor prognosis. Few studies have reported IR in female reproductive system malignancies. This study investigated the prognostic value of IR and systemic inflammation in this population. METHODS: A prospective multicenter real-world cohort study involving 571 patients diagnosed with female reproductive system malignancies was conducted. Lipid ratios (low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol [LHR], total cholesterol/HDL-cholesterol [TCHR], triglyceride/HDL-cholesterol [TGHR], fasting triglyceride/glucose [TyG]) were used to reflect IR. Optimal cut-off values were determined using maximally selected rank statistics. The Kaplan-Meier and Cox regression were used to calculate the hazard ratios for overall survival. RESULTS: Over half (55.90%) of the 571 patients with female reproductive system malignancies (mean age: 52 years) had cervical cancer. Both IR and inflammation were negatively correlated with overall survival in female reproductive system cancer patients. Multivariate survival analysis showed that patients with high LHR (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.01-2.25, p = .046), high TCHR (HR: 1.90, 95% CI:1.22-2.95, p = .005), high TGHR (HR: 1.66, 95% CI:1.17-2.36, p = .004), high TyG (HR: 1.64, 95% CI:1.13-2.40, p = .010), high neutrophil lymphocyte ratio (NLR, HR: 2.03, 95% CI:1.44-2.86, p = .004) were significantly associated with worse prognosis. By calculating the concordance index of the four IR surrogate indicators, TyG was the most valuable indicator for the prognosis of patients with malignant tumors of the female reproductive system. High TyG combined with high NLR had improved prognostic value (HR: 3.22, 95% CI: 1.97-5.26, p < .001). CONCLUSIONS: IR can be used as an independent predictor of prognosis in the female reproductive system malignancy population regardless of the IR substitution index. The combination of TyG and NLR could better predict the prognostic outcomes of women with breast cancer.

A comprehensive analysis of the association between anemia and systemic inflammation in older patients with cancer.

PURPOSE: Our study aimed to comprehensively analyze the association between anemia and systemic inflammation in older patients with cancer. METHODS: This multicenter prospective cohort study included 4955 older patients with cancer between 2013 and 2020. Logistic regression analysis was performed to investigate risk factors of anemia, reporting odds ratios (ORs), and 95% confidence intervals (CIs). Comprehensive survival analyses, including Kaplan-Meier curve, Cox proportional risk model, and subgroup analysis, were performed. RESULTS: The participants' median age was 70.0 (interquartile range [IQR]=67.0-74.0) years, with 3293 (66.5%) males and 1662 (33.5%) females. There were 1717 (34.7%) older patients with cancer diagnosed with anemia. High neutrophil-to-lymphocyte ratio (NLR) was an independent risk factor associated with anemia (adjusted OR=1.97, 95%CI=1.73-2.24, P<0.001). In older patients with cancer and different anemia levels, the median overall survival was significantly shorter in those with a high NLR. In multivariate Cox analysis, high NLR served as a negative factor, independently affecting survival. The anemia-inflammation prognostic grading system showed a significant survival discriminative performance in older patients with cancer. After adjusting for confounders, high grades were independent risk factors for survival (grade 2: hazard ratio [HR] = 1.38, 95%CI = 1.26-1.52, P<0.001; grade 3: HR=1.82 95%CI = 1.59-2.09, P<0.001). This grading system was beneficial in determining survival in patients with lung, digestive tract, and urogenital cancers. CONCLUSIONS: Increased systemic inflammation is an independent risk factor for anemia. A high inflammatory status is also associated with poor survival in older cancer patients at different anemia levels. The anemia-inflammation grading system is beneficial for determining the prognosis in older patients with cancer.

Association of the age of onset of metabolic syndrome with the risk of all cancer types.

BACKGROUND: The association between the age at onset of metabolic syndrome and cancer risk remains unknown. This study explored the association between age at metabolic syndrome onset and the risk of overall and site-specific cancer incidence. METHODS: This study included 31,688 participants with new-onset metabolic syndrome and 31,688 participants matched according to sex, age (±1 y), and examination year among the 179,328 participants who underwent Kailuan health examinations from 2006 to 2017 in Tangshan, China. Weighted Cox regression was used to calculate the hazard ratios and 95% confidence intervals of new-onset metabolic syndrome for overall and site-specific cancer incidence across age groups. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating the risk factors from the population. RESULTS: During an average follow-up period of 10.22 y, we identified 2,710 cases of cancer and 4,218 deaths that occurred before the diagnosis of cancer. With an increase in metabolic syndrome onset age, the hazards of overall cancer incidence were gradually attenuated. The average hazard ratios (95% confidence intervals) of overall cancer were 1.94 (1.25-2.99) for metabolic syndrome onset age <45 year old, 1.41 (1.15-1.71) for age 45-54 years old, 1.38 (1.11-1.73) for age 55-64 years old, and 1.07 (0.89-1.28) for age ≥65 years old, respectively (p for interaction = 0.005). Similar results were obtained for colorectal, liver, and breast cancers in the site-specific analysis. CONCLUSIONS: New-onset metabolic syndrome was associated with a higher risk of overall cancer and incidence of several types of cancer, and the associations were stronger with a younger age of onset. TRIAL REGISTRATION: Kailuan Study, ChiCTR2000029767 (Registered February 12, 2020, https://www.chictr.org.cn/showprojEN.html?proj=48316).

A promising prognostic grading system incorporating weight loss and inflammation in patients with advanced cancer.

BACKGROUND: Involuntary weight loss and increased systemic response are frequently observed in patients with cancer, especially in advanced stages. This study aimed to develop a powerful weight loss and inflammation grading system (WLAIGS) and investigate its prognostic performance in patients with advanced cancer. METHODS: This multicentre prospective cohort study included 11 423 patients with advanced cancer. A 4 × 4 matrix representing four different per cent weight loss (WL%) categories within each of the four different neutrophil-to-lymphocyte ratio (NLR) categories (16 possible combinations of WL% and NLR) was constructed. The WLAIGS consisted of four grades, with hazard ratios (HRs) for overall survival (OS) gradually increasing from grade 1 to grade 4. Survival analyses, including Kaplan-Meier curve, Cox proportional hazards regression, and sensitivity analysis, were performed to investigate the association between WLAIGS and OS. The secondary outcomes were short-term survival, malnutrition, and quality of life. Two internal validation cohorts with a 7:3 ratio were used to validate the results. RESULTS: The median age of patients with advanced cancer in our study was 59.00 (interquartile range, 50.00-66.00) years. There were 6877 (60.2%) and 4546 (39.8%) male and female participants, respectively. We totally recorded 5046 death cases during the median follow-up of 17.33 months. The Kaplan-Meier curve showed that the survival rate decreased from grade 1 to grade 4 in patients with advanced cancer (log-rank P < 0.001). The WLAIGS was an independent risk factor associated with OS adjusting for confounders, with HRs increasing from 1.20 (95% confidence interval (CI), 1.11-1.29; P < 0.001) in grade 2, 1.48 (95% CI, 1.38-1.60; P < 0.001) in grade 3 to 1.73 (95% CI, 1.58-1.89; P < 0.001) in grade 4. In each weight loss% group (2.5 ≤ WL% < 6.0; 6.0 ≤ WL% < 11.0, WL% ≥ 11.0), a NLR above 3 was associated with shorter survival and served as an independent prognostic predictor. The risk of short-term mortality, malnutrition, and poor quality of life increased with WLAIGS grade. Two internal validation cohorts confirmed that the WLAIGS independently identified the survival of patients with advanced cancer. CONCLUSIONS: The WLAIGS, which reflects malnutrition and systemic inflammation status, is a robust and convenient tool for predicting the prognosis of patients with advanced cancer.

Association between insulin resistance related indicators with the prognosis of patients with colorectal cancer.

BACKGROUND: The progression of colorectal cancer (CRC) has been linked to metabolism alteration. Because insulin resistance (IR) is the basic mechanism of metabolism alteration, IR related indicators are considered to be associated with prognostic of CRC. In this study, we compared the prognostic values of common IR related indicators for CRC and selected the best one. Moreover, we explored the association between that indicator and CRC prognosis and possible interactive covariates. METHODS: Medical records of patients with CRC (n = 1765) were retrieved from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. We compared the prognostic values of IR related indicators and select the best one using concordance index (C-index) and area under curve (AUC). Using Cox proportional hazard regression models, we evaluated the association between that indicator and CRC prognosis. Interaction tests were performed to evaluate possible interactions among covariates and the IR related indicator. RESULTS: Results of C-index and AUC indicated that the ratio of low-density lipoprotein-to-high-density lipoprotein (LHR) showed the highest ability to predict the prognosis of patients with CRC. LHR independently predicted CRC prognosis [hazard ratio (HR) = 1.14; 95 % confidence interval (CI) = 1.05-1.22; P = 0.001]. The interactions between LHR, and age (<65 vs. ≥65; P for interaction = 0.001) or neutrocyte-to-lymphocyte ratio (NLR) (<3 vs. ≥3; P for interaction = 0.055) were also observed. CONCLUSION: LHR was found to be the best IR related indicators to predict prognosis of CRC, and it was negatively correlated with the prognosis of patients with CRC. NLR and aging might interact with LHR.

Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.