Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for ...asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.
Telomeres are crucial in the maintenance of chromosome integrity and genomic stability. A series of epidemiological studies have examined the association between telomere length and the risk of ...cancers, but the findings remain conflicting. We performed literature review and meta-analysis to demonstrate the relationship between telomere length and cancer risk. A total of 23,379 cases and 68,792 controls from 51 publications with 62 population studies were included in this meta-analysis to assess the association between overall cancer or cancer-specific risk and telomere length. General association and dose-response relationship were evaluated based on two and three groups, respectively. The estimates of association were evaluated with odds ratios and 95% confidence intervals by the random-effects or fixed-effects model based on heterogeneity test. We observed a non-significant association between short telomeres and overall risk of cancer. Convincing evidence was observed for the association of short telomeres with an increased risk of gastrointestinal tumor and head and neck cancer. Significant dose-response associations were also observed for gastrointestinal tumor and head and neck cancer. Our findings indicate that telomeres may play diverse roles in different cancers, and short telomeres may be risk factors for the tumors of digestive system.
Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed ...to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk.
In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 10−8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low quintile 1 of the polygenic risk score, intermediate quintile 2–4 of the polygenic risk score, and high quintile 5 of the polygenic risk score). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor.
The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10−5) showed the strongest association with gastric cancer risk (p=7·56 × 10−10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio HR 1·54 95% CI 1·22–1·94, p=2·67 × 10−4) and a high genetic risk (2·08 1·61–2·69, p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 1·46–2·83, p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 0·29–0·99, p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62–1·56).
Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer.
National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.
The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We ...aimed to identify and evaluate HCC‐associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three‐phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para‐carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case–control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR‐20a‐5p, miR‐25‐3p, miR‐30a‐5p, miR‐92a‐3p, miR‐132‐3p, miR‐185‐5p, miR‐320a and miR‐324‐3p) were significantly overexpressed in the HBV‐positive HCC patients compared with the HBV‐positive cancer‐free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR‐192‐5p, miR‐21‐5p and miR‐375) in two prospective cohorts. Our meta‐analysis revealed that four miRNAs (miR‐20a‐5p, miR‐320a, miR‐324‐3p and miR‐375) could be used as preclinical biomarkers (pmeta < 0.05) for HCC. The expression profile of the eight‐miRNA panel can be used to discriminate HCC patients from cancer‐free controls, and the four‐miRNA panel (alone or combined with AFP) could be a blood‐based early detection biomarker for HCC screening.
What's new?
Half of all deaths from hepatocellular carcinoma (HCC) occur in China. But while early detection of the disease could improve survival, preclinical diagnostic biomarkers are lacking. Using tissue and plasma samples from HCC patients and plasma samples from prospective cohorts, the authors of this study evaluated the diagnostic and predictive potential of miRNAs. A panel of eight miRNAs dysregulated during HCC development successfully distinguished HCC patients from controls, while a panel of four miRNAs was found to have preclinical potential. The newly described miRNA panels could aid in the detection of HCC before the disease is otherwise clinically apparent.
Dietary and genetic factors are considered to be associated with UGI cancer risk. However, examinations of the effect of healthy diet on UGI cancer risk and the extent to which healthy diet modifies ...the impact of genetic susceptibility on UGI cancer remains limited. Associations were analyzed through Cox regression of the UK Biobank data (
= 415,589). Healthy diet, based on "healthy diet score," was determined according to fruit, vegetables, grains, fish, and meat consumption. We compared adherence to healthy diet and the risk of UGI cancer. We also constructed a UGI polygenic risk score (UGI-PRS) to assess the combined effect of genetic risk and healthy diet. For the results high adherence to healthy diet reduced 24% UGI cancer risk (HR
: 0.76 (0.62-0.93),
= 0.009). A combined effect of high genetic risk and unhealthy diet on UGI cancer risk was observed, with HR reaching 1.60 (1.20-2.13,
= 0.001). Among participants with high genetic risk, the absolute five-year incidence risk of UGI cancer was significantly reduced, from 0.16% to 0.10%, by having a healthy diet. In summary, healthy diet decreased UGI cancer risk, and individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy diet.
For any given phenotype, there were a large number of underlying genetic loci, each exhibiting only small effect, but in combination, they could explain a significant proportion of the variance of ...phenotypes in the general population. ...by aggregating the effects of relevant genetic loci into a single indicator, polygenic scores (PGSs) (also referred to polygenic risk scores PRSs, or genetic or genomic risk scores GRSs for diseases) have emerged as a quantitative measure to predict an individual's genetic predisposition to a phenotype. 12 By comparing germline de novo mutations between offspring in families conceived spontaneously and assisted reproductive technology (ART) based on whole-genome sequencing trios, Wang et al13 demonstrated that the increased mutations in offspring conceived by ART were primarily originated from fathers. ...a trio approach enables accurate phasing and the assignment of the parental origin of alleles to show parent-of-origin effects. ...there may be potential unintended consequences of ESPS, such as selecting for adverse traits as a result of pleiotropy. ...ESPS is not ready for clinical uses, although disease risk for individuals with extreme PRSs equivalent to monogenic mutations makes meaningful contribution to genetic risk prediction and aforementioned medical applications. ...to address the clinical validity of PGSs, evaluations are required in the clinical or public health context, such as prospective cohorts considering other non-genetic factors for absolute risk estimation, randomized trials with clinically meaningful outcomes, and health economic evaluations or feasibility studies.
Recent findings that human serum contains stably expressed microRNA (miRNA) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide ...serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of non-small-cell lung cancer (NSCLC).
To control disease heterogeneity, we used patients with stages I to IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 patients with longer survival (alive and mean survival time, 49.54 months) and 30 patients with shorter survival matched by age, sex, and stage (dead and mean survival time, 9.54 months). The detected serum miRNAs then were validated in 243 patients (randomly classified into two subgroups: n = 120 for the training set, and n = 123 for the testing set).
Eleven serum miRNAs were found to be altered more than five-fold by Solexa sequencing between longer-survival and shorter-survival groups, and levels of four miRNAs (ie, miR-486, miR-30d, miR-1 and miR-499) were significantly associated with overall survival. The four-miRNA signature also was consistently an independent predictor of overall survival for both training and testing samples.
The four-miRNA signature from the serum may serve as a noninvasive predictor for the overall survival of NSCLC.
Little prospective evidence exists about whether a combination of healthy lifestyle factors is related to a considerable reduction of liver cancer risk.
Based on the prospective China Kadoorie ...Biobank (CKB) cohort with a total of 492,640 Chinese adults, we examined the associations of five lifestyle factors with risk of liver cancer. Low-risk lifestyle factors were defined as non-smoking, non-drinking, median or higher level of physical activity, a healthy diet, and waist-to-hip ratio (WHR) < 0.90 for men and <0.85 for women.
During a median of 10.12 years of follow-up, 2529 liver cancer events were observed. There was a significant decrease in liver cancer risk with the increasing of the healthy lifestyle index scores (P < 0.001). Participants with a favourable lifestyle (4 or 5 healthy lifestyle factors) had a 43% reduced liver cancer risk compared with those with an unfavourable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.57 95% CI, 0.47-0.68). The cumulative protective effect of a healthy lifestyle on liver cancer appeared to be more dramatic for patients with hepatitis B surface antigen (HBsAg) positive, the individuals at high risk of liver cancer.
Individuals adhering to a favourable lifestyle was associated with a considerable absolute risk reduction of liver cancer.
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.
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.
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 constructed 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.
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.
Recent evidence indicates that small noncoding RNA molecules known as microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Mutation, misexpression, and altered mature miRNA processing ...are implicated in carcinogenesis and tumor progression. Because SNPs in pre-miRNAs could alter miRNA processing, expression, and/or binding to target mRNA, we conducted a systematic survey of common pre-miRNA SNPs and their surrounding regions and evaluated in detail the association of 4 of these SNPs with the survival of individuals with non-small cell lung cancer (NSCLC). When we assumed that disease susceptibility was inherited as a recessive phenotype, we found that the rs11614913 SNP in hsa-mir-196a2 was associated with survival in individuals with NSCLC. Specifically, survival was significantly decreased in individuals who were homozygous CC at SNP rs11614913. In the genotype-phenotype correlation analysis of 23 human lung cancer tissue samples, rs11614913 CC was associated with a statistically significant increase in mature hsa-mir-196a expression but not with changes in levels of the precursor, suggesting enhanced processing of the pre-miRNA to its mature form. Furthermore, binding assays revealed that the rs11614913 SNP can affect binding of mature hsa-mir-196a2-3p to its target mRNA. Therefore, the rs11614913 SNP in hsa-mir-196a2 may be a prognostic biomarker for NSCLC. Further characterization of miRNA SNPs may open new avenues for the study of cancer and therapeutic interventions.
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