Construction and evaluation of the functional polygenic risk score for gastric cancer in a prospective cohort of the European population / 中华医学杂志(英文版)

BACKGROUND@#A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities.@*METHODS@#We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer.@*RESULTS@#During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk.@*CONCLUSION@#These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.

Prognostic values of dynamical monitoring of early weight change in patients with severe trauma / 中华创伤杂志

Objective To investigate the association between body weight daily fluctuation and prognosis in severe trauma patients and evaluate the values of dynamical monitoring of early weight change in treatment of severe trauma.Methods A prospective cohort study was made on 65 patients with severe trauma treated between June 2015 and December 2015.There were 41 males and 24 females,with age of (54 ± 17)years.When admitted to the emergency intensive care unit (EICU),the patients were with body mass index (BMI) for (22.0 ±2.7) kg/m2,injury severity score (ISS) for (22 ±5) points,as well as acute physiology and chronic health evaluation (APACHE) Ⅱ for (15 ± 6)points.According to the survival status during hospitalization,the patients were distributed to death group (9 patients) and survival group (56 patients).Daily body weight was measured from admission by using a weighing scale to evaluate the difference of daily body weight change between two groups.The correlation between daily body weight change and volume change as well as the relationship between daily body weight change tendency and prognosis were evaluated.Results Overall,the variation of weight was negatively correlated with ICU stay in two groups.The weight variations in death group and survival group were 0.4 (0.2,0.8) kg and-0.2 (-0.7,0.2) kg,respectively (P ＜ 0.01).The cumulative weight variation between two groups within one week was 5.02 kg (95％ CI 3.97-6.07,P ＜0.01).The change of body weight was moderately correlated with corresponding fluid balance (r =0.69,P ＜ 0.01).According to the Logistic regression analysis,daily weight gain within one week was found to be positively associated with ICU mortality (OR =3.05,P ＜ 0.05).Conclusions The body weight is negatively correlated with ICU stay in severe trauma patients.The body weight change within one week in EICU is closely correlated with fluid balance and body weight increase may elevate the risk of ICU mortality.