Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations

Background Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort. Results The GCRS using 11 questionnaire-based variables demonstrated a Harrell’s C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants. Conclusions The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS

Genetic risk, metabolic syndrome, and gastrointestinal cancer risk: A prospective cohort study

Abstract Background Gastrointestinal (GI) cancer risk has been associated with metabolic syndrome (MetS), a surrogate indicator for unhealthy lifestyles, and a number of genetic loci, but the combined effect of MetS and genetic variants on GI cancer risk is uncertain. Methods We included 430,036 participants with available MetS and genotype data from UK Biobank. During the follow‐up time, 5494 incident GI cancer cases, including esophageal cancer, gastric cancer, and colorectal cancer, were identified. We created a GI polygenic risk score (GI‐PRS) for overall GI cancer derived from three site‐specific cancer PRSs. Cox proportional hazards regression was used to estimate the associations of MetS and GI‐PRS with the risk of GI cancer. Results MetS was significantly associated with 28% increment in GI cancer risk (hazard ratio [HR]MetS vs. non‐MetS: 1.28, 95% confidence interval [CI]: 1.21–1.35, p < 0.0001), whereas a high GI‐PRS (top quintile) was associated with 2.28‐fold increase in risk (HRhigh vs. low: 2.28, 95% CI: 2.09–2.49, p < 0.0001). Compared with participants without MetS and at low genetic risk (bottom quintile of GI‐PRS), those with MetS and at high genetic risk had 2.75‐fold increase in GI cancer risk (HR: 2.75, 95% CI: 2.43–3.12, p < 0.0001). Additionally, MetS in comparison with no MetS had 1.49‰, 2.75‰, and 3.37‰ absolute risk increases in 5 years among participants at low, intermediate (quintiles 2–4 of GI‐PRS) and high genetic risk, respectively, representing the number of subjects diagnosed as MetS causing a new GI cancer case in 5 years were 669, 364, and 296, respectively. Conclusions Metabolic and genetic factors may jointly contribute to GI cancer risk and may serve as predictors by quantitative measurements to identify high‐risk populations of GI cancer for precise prevention

Significantly improved weldability in laser welding of additively manufactured haynes 230 superalloys by tailoring microstructure

Owing to restrictions on forming dimensions, laser powder bed fusion (LPBF) components will continue to require laser welding in the future. The post-weld thermal cracking of LPBF-Haynes 230 superalloys has become a key issue hindering their assembly in service. In this study, it was found that both the continuous TCP phase and M5Si3 silicides near the crack have a large interface strain with the matrix. Replacing the C and Si atoms with B atoms at the crack reduces the melting point of the carbides and silicides at the grain boundaries (GBs), thereby inducing solidification cracking under the residual tensile stress in the weld waist. The weldability of the alloy is influenced by the grain characteristics of the base metal (BM). Compared to parallel welds, vertical welds are inherited from the BM and exhibit smaller grains. Moreover, by reducing the heat treatment (HT) time and temperature, the grain size and grain misorientation of the BM are reduced and inherited into the weld. The GB area of the weld increases by 37% and the GB energy decreases by 7.3%, increasing the resistance to crack extension. In addition, the decreased HT temperature inhibits the carbide growth at the GBs, thereby reducing the interface strain between the matrix and carbides in the heat-affected zone and correspondingly its cracking sensitivity. This study provides theoretical guidance for improving the laser weldability of LPBF superalloys and will help accelerate the successful application of LPBF superalloy assemblies in engines

Association analysis between haplotypes of and gastric cancer susceptibility.

<p>^a SNP order: rs10464867, rs14448, and rs1063053.</p><p>^b Derived from logistic regression with an adjustment for age, sex, smoking and drinking status.</p><p>Association analysis between haplotypes of and gastric cancer susceptibility.</p

Genetic Variation in the 3'-Untranslated Region of <i>NBN</i> Gene Is Associated with Gastric Cancer Risk in a Chinese Population

<div><p><i>NBN</i> plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the <i>NBN</i> gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the <i>NBN</i> gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in <i>NBN</i> and gastric cancer risk in a case–control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71–0.94; <i>P</i> = 4.71×10⁻³). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59–0.88], <i>P</i> = 1.07×10⁻³), and male individuals (per-allele OR = 0.73[0.62–0.87], <i>P</i> = 3.68×10⁻⁴). We further conducted a haplotype analysis and identified that the <i>NBN</i> A_rs10464867G_rs14448G_rs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65–0.89], <i>P</i> = 6.39×10⁻⁴). In summary, these findings indicate that genetic variants at <i>NBN</i> gene may contribute to gastric cancer susceptibility and may further advance our understanding of <i>NBN</i> gene in cancer development.</p></div