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The recommendation encouraging patients with cancer to keep a normal body mass index (BMI) is largely extrapolated from data on risk of developing cancer. We tested the prospective association between peri-diagnostic (within 1 year post-diagnosis) BMI and all-cause mortality in patients with incident cancers. During 7.2 years of follow-up, 42% (48,340) of the 114 430 patients with cancer died. Spline analysis revealed that compared with a BMI of 22.5, a BMI lower than 22.5 was associated with increased risk of all-cause mortality across 24 cancer types. A BMI higher than 22.5 was associated with reduced all-cause mortality, while a non-linear association was observed; the lowest risk was found at a BMI of 29.6-34.2, and the risk started to return to and above unity at very high BMI values. The reduced mortality risk of high BMI was observed in 23 of 24 cancer types and maintained after attempts to remove potential selection bias, confounding by smoking and comorbidities, and reserve causality. Compared with a normal BMI of 18.5-24.9, the hazard ratios were 0.85 (95% confidence interval [CI], 0.83-0.87) for an overweight BMI (25-29.9) and 0.82 (0.80-0.85) for an obese BMI (≥30), and the associations were generally consistent across cancer types and various subgroups. Obese BMI was associated with increased life expectancy, up to 6 years among men and 3 years among women. In conclusion, while overweight/obese BMI increases the risk of developing cancer in the general population, overweight/obese peri-diagnostic BMI was associated with longer survival in cancer patients.

About 30% of patients undergoing nephrectomy for renal cell carcinoma (RCC) experience disease recurrence. We profiled miRNAs dysregulated in clear-cell (cc) RCC tumor tissues and predictive of recurrence. The expression levels of 800 miRNAs were assessed in paired tumor and normal tissues from a discovery cohort of 18 ccRCC patients. miRNAs found to be differentially expressed were examined in a validation set of 205 patients, using real-time quantitative PCR. Tumor-normal data from 64 patients in The Cancer Genome Atlas were used for external validation. Twenty-eight miRNAs were consistently dysregulated in tumor tissues. On dichotomized analysis, patients with high levels of miR-155-5p and miR-210-3p displayed an increased risk for ccRCC recurrence (hazard ratio, 2.64; 95% CI, 1.49 to 4.70; P = 0.0009; and hazard ratio, 1.80; 95% CI, 1.04 to 3.12; P = 0.036, respectively) and a shorter median recurrence-free survival time than did patients with low levels [P

Background Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine and may promote cancer growth, especially among those with neoplastic alterations. Objective We investigated the prospective association between synthetic compared with natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. Design In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food-frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 y, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted HRs and ORs with 95% CIs. Results Synthetic folic acid intake was positively associated with a risk of recurrence among NMIBC patients (medium compared with low intake-HR: 1.72; 95% CI: 1.20, 2.48; P = 0.003; high compared with low intake-HR: 1.80; 95% CI: 1.14, 2.84; P = 0.01). Patients with a higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium or high compared with low-OR: 2.08; 95% CI: 1.08, 4.02; P = 0.03). In contrast, natural folate intake tended to be inversely associated with the risk of progression (medium or high compared with low-HR: 0.68; 95% CI: 0.44, 1.04; P = 0.08). Conclusions A high intake of synthetic folic acid, in contrast to the natural forms, is associated with an increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, which suggests that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation with regard to folate intake among NMIBC patients.

In our previous breast cancer case control study in Hispanics, we found 14 metabolites whose levels differed between cases and controls. To validate the results, we carried out a nested case control study of 100 incident breast cancer and 100 matched healthy women identified from the Mano-A-Mano Mexican American Cohort study. With the adjustment of parity, education, birth place, language acculturation, BMI category, smoking, drinking, physical activity, and sitting time, 4 metabolites were associated with breast cancer risk: 3-hydroxyoctanoate (Odds ratio (OR) = 1.51, 95% confidence interval (CI): 1.10, 3.47), 3-hydroxybutyrate (BHBA) (OR = 1.42, 95%CI: 1.01, 3.72), linoleate (18:2n6) (OR = 1.39, 95% CI: 1.07, 4.04), and bilirubin (OR = 0.54, 95%CI: 0.42, 0.95). Then, we used 3 non-redundant metabolites, namely 3-hydroxyoctanoate, linoleate (18:2n6), and bilirubin, to generate a metabolic risk score. Increased metabolites risk score was associated with a 1.67-fold increased risk of breast cancer (OR = 1.67, 95%CI: 1.32, 3.94). And the significant association was more evident among those who were diagnosed with cancer earlier during the follow-up (≤ 5 years) than their counterparts. In conclusion, we identified four significant metabolites which may help elucidate metabolic pathways that contribute to breast carcinogenesis. Our findings warrant further replication efforts.

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p

Clinical factors predicting pulmonary complications after lung resection have been well described, whereas the role of genetics is unknown. The vascular endothelial growth factor (VEGF) signaling pathway has been linked to acute lung injury. We hypothesized that genetic variations in this pathway may be associated with postoperative pulmonary complications after lung resection.One hundred ninety-six single nucleotide polymorphisms (SNPs) in 17 genes in the VEGF pathway were genotyped in a discovery set of 264 patients and a replication set of 264 patients who underwent lobectomy for lung cancer. Multivariable analysis adjusting for baseline clinical factors was used to identify SNPs associated with pulmonary complications. Cumulative and classification and regression tree (CART) analyses were used to further stratify risk groups.The overall number of pulmonary complications was 164/528 (31%). The effects of 6 SNPs were consistent in the discovery and replication sets (pooled p value0.05). The rs9319425 SNP in the VEGF receptor gene FLT1 resulted in a 1.50-fold increased risk (1.15-1.96; p=0.003). A cumulative effect for the number of risk genotypes and complications was also evident (p0.01). Patients carrying 5 risk genotypes had a 5.76-fold increase in risk (2.73-12.16; p=4.44×10(-6)). Regression tree analysis identified potential gene-gene interactions between FLT1:rs9319425 and RAF1:rs713178. The addition of the 6 SNPs to the clinical model increased the area under the receiver operating characteristic curve by 6.8%.Genetic variations in the VEGF pathway are associated with risk of pulmonary complications after lobectomy. This may offer insight into the underlying biological mechanisms of pulmonary complications.

Objectives The purpose of this study was to explore the role of single nucleotide polymorphisms (SNPs) in cytokine signaling genes and to compare them with clinical outcomes in surgical patients with non–small cell lung cancer (NSCLC). Methods SNPs of the cytokine signaling pathway were analyzed using peripheral blood of 722 patients who underwent resection of stage I to III NSCLC between 1995 and 2009. Cox proportional hazard analyses were performed to identify SNPs associated with overall survival (OS) and risk of recurrence. Internal validation using bootstrap analysis selected SNPs for unfavorable genotype and survival tree analysis. Results Seventeen and 9 SNPs were independently associated with OS and recurrence, respectively. Patients with ≥9 unfavorable genotypes experienced worse OS (median, 41 months) than patients with 7 to 8 (89 months) and ≤6 (153 months) after median follow-up of 71 months ( P = 2.86 × 10 −23 ). Patients with ≤3 unfavorable genotypes had greater time to recurrence (median not reached) than those with 4 to 6 (114 months) and ≥7 (44 months; P = 1.3 × 10 −5 ). Survival tree analysis classified patients into 3 risk groups. Patients in the intermediate- (median OS, 82 months) and high-risk groups (43 months) had worse survival than the low-risk group (176 months; P = 5.51 × 10 −20 ). Median time to recurrence was worse in the intermediate- (114 months) and high-risk groups (58 months) than the low-risk group (median not reached; P = 2.52 × 10 −9 ). Conclusions Genetic variants in cytokine signaling pathways were associated with clinical outcomes in NSCLC patients treated with surgery individually and cumulatively. Further studies are necessary to elucidate our findings and translate them into the clinical setting.

We aimed to identify new serum biomarkers of esophageal adenocarcinoma (EAC).We performed metabolomic analyses of serum samples from 2 sets of case-control pairs in the discovery phase, each consisting of 30 patients with histologically confirmed EAC (cases) from the University of Texas MD Anderson Cancer Center and 30 matched subjects without EAC (controls). We identified metabolites whose levels differed significantly between cases and controls and validated those with the greatest difference in an analysis of 321 EAC cases and 331 controls. We generated a metabolite risk score (MRS) for the metabolites.The levels of 64 metabolites differed significantly between EAC cases and controls in the discovery phase. The metabolites with the greatest difference were amino acid L-proline (LP), ketone body 3-hydroxybutyrate (BHBA), and carbohydrate D-mannose (DM); these differences were confirmed in the validation set. Cases had lower mean levels of LP than controls (22.78 ± 6.79 μg/mL vs 28.24 ± 8.64 μg/mL; P.001) and higher levels of BHBA (18.06 ± 17.84 μg/mL vs 7.73 ± 9.92 μg/mL; P.001) and DM (9.87 ± 4.28 μg/mL vs 6.28 ± 3.61 μg/mL; P.001). Levels of DM were significantly higher in patients with late-stage EAC than early-stage EAC (10.61 ± 4.79 μg/mL vs 8.97 ± 3.36 μg/mL; P = .005). Higher levels of LP were associated with significant decrease in risk of EAC (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.18-0.38). A significant increase in risk of EAC was associated with higher levels of BHBA (OR, 4.05; 95% CI, 2.84-5.78) and DM (OR, 7.04; 95% CI, 4.79-10.34). Levels of all 3 metabolites associated with EAC risk in a dose response manner; the level of risk conferred by the metabolites increased jointly with smoking status and body mass index. Individuals with high MRS had significant (7.76-fold) increase in risk of EAC vs those with low MRS. Smokers with high MRS had the greatest risk of EAC (OR, 23.40; 95% CI, 10.95-50.00), compared with never smokers with low MRS.On the basis of a case vs control metabolic profile analysis, levels of LP, BHBA, and DM are associated with risk of EAC. These markers might be used as risk and prognostic factors for patients with EAC.