Carcinoma In Chinese Population Research Articles

A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population.

This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS). A case-control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta-analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models. A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84-0.89; AUC: 0.85, 95% CI: 0.81-0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60-0.67; AUC: 0.65, 95% CI: 0.60-0.71). A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at-risk individuals for precise prevention.

Underlying effect of SMAD4 gene polymorphism on risk prediction of papillary thyroid carcinoma in Chinese population

ObjectiveThis research intends to explore how variations in the SMAD4 gene impact papillary thyroid carcinoma (PTC) among patients in China. MethodsThe rs10502913 and rs12968012 polymorphisms were genotyped in 405 subjects using SNP-scan high-throughput technology. Differential mRNA expression of SMAD4 was analyzed using data from TCGA and GSE33630, and protein level expression differences were analyzed using immunohistochemistry. ResultsThe results showed that SMAD4 mRNA expression was lower in thyroid cancer (THCA) tissues than in normal tissues. Immunohistochemical results showed that the expression level of SMAD4 in normal tissue, thyroid papillary carcinoma tissue and poorly differentiated tissue was significantly different. We found that SMAD4 mismatch variants (rs10502913 and rs12968012) were associated with PTC susceptibility. Specifically, the SMAD4-rs10502913 genotypes (GA and AA) showed a notable correlation with a lower likelihood of PTC in comprehensive and segmented studies (genotype GA: OR (95% CI) = 0.270 (0.077–0.950), p = 0.041; genotype AA: OR (95% CI) = 0.103 (0.025–0.416), p = 0.001). We categorized the immunohistochemical results according to genotype and found that rs10502913-GG protein level was expressed at the lowest level, and both GA and AA were higher than GG (GG vs. AA, P < 0.05), and rs12968012-CG protein level was expressed at the lowest level, and both GG and CC were higher than CG (GG vs. CG, P < 0.01). ConclusionTwo missense variants of SMAD4 (rs10502913 and rs12968012) are associated with reduced risk of papillary thyroid carcinoma, possibly by reducing protein expression leading to susceptibility to papillary thyroid carcinoma.

Risks and Clinical Predictors of Hepatocellular Carcinoma in Chinese Populations: A Real-World Study of 10,359 Patients in Six Medical Centers.

Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China. A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up. Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis. The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.

Epidemiology, treatments, and related biomarkers of locally advanced or metastatic urothelial carcinoma in Chinese population: A scoping review.

Bladder cancer is the 13th most common cancer in China with the predominant histologic type being urothelial carcinoma (UC). Locally advanced and metastatic (la/m) UC accounts for 12% of UC and the five-year survival rate is only 39.4%, imposing a significant disease and economic burden on the patients. The aim of this scoping review is to synthesize existing evidence of epidemiology, the landscape of treatment options and associated efficacy and safety profiles, as well as treatment-related biomarkers among Chinese la/mUC patients. A systematic search was conducted on five databases (PubMed, Web of Science, Embase, Wanfang, and CNKI) from January 2011 to March 2022 based on the scoping review criteria in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. A total of 6211 records were identified, and further review resulted in 41 relevant studies that met all criteria. Additional searches were conducted on epidemiology and treatment-related biomarkers of bladder cancer to supplement the evidence. Among 41 studies, 24 reported on platinum-based chemotherapy, eight on non-platinum-based chemotherapy, six on immunotherapy, two on targeted therapy, and one on surgery. Efficacy outcomes were summarized by line of therapy. Treatment-related biomarkers including PD-L1, HER2, and FGFR3 alterations were identified, and the alteration rate of FGFR3 of Chinese UC patients was lower than that of the western patients. Despite chemotherapy has been the main treatment choice for decades, appealing new therapeutic strategiesincluding ICIs, targeted therapies and ADCs were applied in clinical practice. Further research on epidemiology and treatment-related biomarkers of la/mUC patients is needed given only a limited number of studies have been identified thus far. High genomic heterogeneity and complexity of molecular features were observed among la/mUC patients; thus, further studies are required to identify critical drivers and promote potential precise therapies.

558P Molecular subtyping endometrial carcinoma in Chinese population applying an NGS-based classifier and its association with prognosis

Molecular subtypes of EC is widely recognized and applied in clinics. While, it is still less recognized the distribution and prognostic value of molecular subtypes of endometrial carcinoma in Chinese population. An NGS-based classification strategy with reference to these two classifiers was developed and applied for the first time to explore the prognostic correlation of EC patients in China. Formalin-Fixed Paraffin Embedded (FFPE) tissue of 233 EC patients were retrospectively collected from Qilu Hospital, China. Genomic DNA was extracted and subjected to an all-in-one simplified NGS panel covering POLE, TP53 as well as MSI for subtyping. The information for ProMisE classification were also collected. With the median follow-up was 66 (range 7-122) months, overall survival (OS) and disease-specific survival (DSS) were also been analyzed across the subtypes. Base on NGS panel classification, the fractions of POLE, MSI, CNH and CNL group were 8.15%, 18.88%, 11.59% and 61.37%, respectively. 61patients with ProMisE classification available, the fractions of the former subtypes were11.48%, 36.07%, 14.75%, and 37.70% respectively. The OS and DSS was (P=0.046 for OS, P=0.024 for DSS) significantly in the four subtypes based on NGS testing in 131 followed patients. There was no significant difference in OS (P = 0.91) and DSS (P = 0.95) across the four subtypes by ProMisE in 50 followed patients (Table).Table: 558PSurvival analysis results based on the two classifiersNGS-based classifier（N=131）POLEMSICNHCNLP8 years -OS rate100%80.00%50.00%92.26%0.0468 years -DSS rate100%88.89%66.67%100%0.024ProMisE classifier (N=50)8 years -OS rate83.33%89.47%100%80.00%0.918 years -DSS rate100%94.73%100%92.31%0.95 Open table in a new tab The NGS-based strategy was confirmed to effectively classify four prognostically significant subgroups in endometrial cancer patients. Further analysis showed that the clinicopathological features of each molecular subtype were significantly different. All the results confirmed the feasibility of molecular subtyping of EC in clinical practice by a simplified NGS approach.

Abstract 5835: Functional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma

Abstract Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia with a poor prognosis and a high mortality rate [1, 2]. The p63 protein, encoded by TP63, is a master regulator involved in many cell events including cell cycle, DNA damage, cell proliferation, stem cell maintenance, and cell death in different cancer types. ΔNp63α is the dominantly expressed isoform of p63 in squamous cell carcinomas, playing a critical role in tumorigenesis [3, 4]. However, the functional roles of ΔNp63α in ESCC have not been fully elucidated. Our results have revealed that ΔNp63α is highly expressed and up-regulated in ESCC. We have shown that ΔNp63α protein expression plays an oncogenic role in ESCC cells, depletion of which inhibits in vitro cell proliferation and colony formation and greatly suppresses in vivo tumor growth, in a panel of ESCC cell lines and our latest patient-derived organoid cultures, potentially in a differentiation-dependent manner. Glycolysis pathway and two novel downstream signaling pathways of ΔNp63α, MYC/4EBP1 and AKT/NDRG1, are significantly suppressed upon ΔNp63α depletion in ESCC cell lines. Notably, xenografts of ΔNp63α-depleted human ESCC cells show elevated infiltrating cancer-associated fibroblasts (CAFs), which may contribute to tumor suppression by ΔNp63α depletion. These data not only shed light on the ΔNp63α functions and how they contribute to the ESCC tumorigenesis, but also unravel potential therapeutic benefits for ESCC patients in the future. Acknowledgements: We acknowledge DSMZ (German Collection of Microorganisms and Cell Culture) for the KYSE cell lines. We acknowledge the Research Grants Council Theme-Based Research Scheme grant T12-701/17-R to MLL.

Efficacy and safety of pembrolizumab in Chinese patients with recurrent/unresectable/metastatic head and neck squamous cell carcinoma.

e18001 Background: The efficacy and safety of Pembrolizumab in recurrent /unresectable/metastatic head and neck squamous cell carcinoma have been well documented in KEYNOTE-048 and other studies, and the effectiveness of different areas’ population have been shown in related studies. However, there is no native data based on the Chinese population. The purpose of this study was to investigate the efficacy and safety of Pembrolizumab in the treatment of R/U/M head and neck squamous cell carcinoma in Chinese population. Methods: We reviewed patients data from the department of Oral &amp; Maxillofacial Surgery, the Affiliated Hospital of Qingdao University. The patients with R/U/M head and neck squamous cell carcinoma were treated with or without combined chemotherapy / targeted therapy according to their PD-L1 expression status (CPS). Pembrolizumab was infused intravenously with 200mg every 3 weeks for a maximum of 35 cycles. The primary endpoint was Objective Response Rate(ORR). The secondary endpoints were Quality of Life, Safety and Progression Free Survival(PFS). Results: A total of 23 eligible patients with R/U/M head and neck squamous cell carcinoma were included from February 2021 to February 2022, including 18 males (78.26%) and 5 females (21.74%) with a median age of 68 years. The primary sites were oral cavity in 16 cases (69.56%), oropharynx in 4 cases (17.39%), hypopharynx in 1 case (4.35%), and larynx in 2 cases (8.70%). P16 status was positive in 4 cases (17.39%), negative in 12 cases (52.17%), and unknown in 7 cases (30.43%). The expression status of PD-L1 in all patients was known. Patients with CPS ≥ 20 were treated with Pembrolizumab monotherapy and patients with CPS &lt; 20 were treated with Pembrolizumab combined with chemotherapy / targeting therapy, of which 22 (95.65%) were treated with first-line therapy and 1 (4.35%) were treated with second-line therapy. The median follow-up period was 6 months. 15 patients were assessed as remission (as of February 2022), of which 4 (17.39%) showed CR, 11 (47.83%) showed PR, 7 (30.43%) showed SD, and 1 (4.35%) showed PD. ORR was 65.22%, DCR was 95.65%. After 4 cycles of treatment, 14 patients (60.87%) achieved tumor remission and control, and the functional status score (KPS) increased from 65 to 85. The incidences of thyroid dysfunction, skin rash, fatigue, neutropenia and immune pneumonia were 2 (8.70%), 3 (13.04%), 2 (8.70%), 1 (4.35%) and 1(4.35%), respectively. Conclusions: This retrospective data have shown excellent efficacy and safety of pembrolizumab in the Chinese population of R/U/M head and neck squamous cell carcinoma, and provide data support for follow-up related research.Due to the short follow-up time, most of the patients have not yet reached PFS, and follow-up will continue.

The Single Nucleotide Polymorphisms of AP1S1 are Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

BackgroundThe σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population.MethodsA database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.ResultsAP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.ConclusionAP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.

Using the aMAP Risk Score to Predict Late Recurrence Following Radiofrequency Ablation for Hepatocellular Carcinoma in Chinese Population: A Multicenter Study.

ObjectiveThis study was conducted to explore the application of age-male-ALBI-platelets (aMAP) score for predicting late recurrence of hepatocellular carcinoma (HCC) following radiofrequency ablation (RFA) and develop an aMAP score based-nomogram to predict prognosis in Chinese population.Materials and MethodsHCC patients who developed late recurrence following RFA at National Cancer Center (NCC) of China, First Hospital of Shanxi Medical University and Beijing Hospital of Traditional Chinese Medicine from January 2011 to December 2016 were included as a training cohort, and patients who were treated at Affiliated Cancer Hospital of Zhengzhou University between January 2012 and December 2016 were included as an external validation cohort. The optimal cut-off value for aMAP score was determined using X-tile software to discriminate the performance of recurrence-free survival (RFS).ResultsA total of 339 eligible patients were included in this study. Patients were grouped into low-risk (aMAP score ≤64.2), medium-risk (64.3 ≤aMAP score ≤68.6) and high-risk (aMAP score ≥68.7) groups by X-tile plots. The prognostic factors that affected RFS were the number of lesions and aMAP score. A nomogram was constructed to predict the RFS with a C-index of 0.793 (95% CI: 0.744–0.842). The time-dependent receiver operating characteristic curves (t-AUCs) of the nomogram to predict 3, 4 and 5-year RFS were 0.808, 0.820 and 0.764, respectively. The model was then tested with data from an external validation cohort. The calibration curve confirmed the optimal agreement between the predicted and observed values.ConclusionThe aMAP score provided a well-discriminated risk stratification and is an independent prognostic factor for the late recurrence of HCC following RFA. The aMAP score-based nomogram could help to strengthen prognosis-based decision making and formulate adjuvant therapeutic and preventive strategies.

Clinicopathologic characteristics of distinct molecular subtypes of endometrial carcinoma in Chinese population.

e17568 Background: Stratifying endometrial carcinoma (EC) based on molecular profiling is of importance. While, spectrum of molecular subtypes of EC in Chinese population needs to be elucidated. Conventional approaches involve methodologies including Sanger sequencing as well as immunohistochemistry which is highly dependent on experience of pathologists. This study is of first time to display clinical and pathological characters of molecular subtypes of EC which were defined by a simplified NGS panel in Chinese population. Methods: Paraffin-embedded tissues of 135 consented EC patients were retrospectively collected from Qilu Hospital, Shandong Province, China. Genomic DNA was extracted and subjected to a simplified panel covering POLE, TP53 as well as 55 MSI loci for massive parallel sequencing. Mutations annotated as Tier I, II were applied for subtyping. MSI was defined as instability in 22 or more microsatellite loci. Subtypes were stratified as POLE, MSI, TP53-wt or TP53-mut group. Correlations of clinicopathological characters as well as prognosis were further conducted. Results: Histology of collected samples were mostly Endometrioid EC (EEC, 93.33%). Most of samples were at stage I (80%). The fractions of POLE (n=10), MSI (n=29), TP53-wt (n=84) and TP53-mut (n=12) group were 7.41%, 21.48%, 62.22%, and 8.89%, respectively. POLE group was associated with earlier stage (Stage I, 90%), EEC (80%) and less lympho-vascular space invasion (LVSI) (10%). TP53-mutant subtype was correlated to later stage (Stage II-IV, 41.67%), higher grade (G2+G3, 83.33%), serous histology (25%) and higher rate of LVSI (25%). The median follow-up was 74 (1.5-122) months. The 8-year overall (OS) and disease-specific survival (DSS) rate were 100% in POLE group, while only 58.3% and 75% in TP53 mutant cases (P&lt;0.001 for OS, P=0.01 for DSS). Conclusions: Molecular subtypes of EC significantly correlated with clinicopathologic characters, especially with patients’ prognosis. This simplified NGS-panel could accurately delineate different EC subgroups.[Table: see text]

Whole-exome Sequencing Reveals Genetic Underpinnings of Tongue Carcinoma in Chinese Population

Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy, of which the incidence has increased in China in the last decade. Surprisingly, while multiple studies have revealed the mutational features of OTSCC in Western populations, limited data was shown in Asian patients. Herein, we utilized whole-exome sequencing to profile the genetic alterations in 13 Chinese OTSCC and compared them to those from 40 Western patients published in Cancer Discovery. In result, some key driver mutations were observed in both Chinese and Western cohorts, such as TP53 (Chinese 60.0% vs Western 60.0%), FAT1 (Chinese 7.7% vs Western 30.0%), CASP8 (Chinese 7.7% vs Western 10.0%) and NOTCH1 (Chinese 15.4% vs Western 10.0%), while mutations in CDKN2A (23.1%) and NTRK3 (23.1%) were only observed in Chinese patients, indicating these two novel mutations might play vital roles in OTSCC tumorigenesis specifically in Asian population. Mutational signatures depicted both common and distinct features across cohorts. In addition, significant copy number loss was found in 7q22.1, 9q13.1, and focal regions spanning CDKN2A and CDKN2B. FOXP1-TEX261 (2p13.3:3p13) fusion, reported in various cancer types, was firstly observed in OTSCC. Also, we identified numerous actionable mutations with FDA approved targeted. Taken together, our study revealed the mutational features of Chinese OTSCC patients, either similar or distinct to those of Caucasian patients. CDKN2A and NTRK3 were observed as two novel drivers that might play essential roles in tumorigenesis in Chinese patients, and were found as two potential therapeutic targets, rendering it promising to develop novel therapies.

Abstract LB-310: Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population

Abstract Background: Salivary adenoid cystic carcinoma (ACC) and oral tongue squamous cell carcinoma (OTSCC) are rare malignancies with low incidence and dismal prognosis. The molecular underpinnings of these remain poorly understood, particularly in Asian population. Methods: Through a whole-exome sequencing analysis of 13 OTSCC and 30 ACC patients, a systematic overview of the mutational features in single-nucleotide variations, copy number variations and chromosomal variations were illustrated. Results: In addition to the well-characterized alterations previously reported in Caucasian patients, such as TP53 mutations (11/13, 84.6%) in OTSCC and MYB-NFIB fusion in ACC (11/30, 36.7%), we also observed several novel genetic changes, including FOXP1-TEX261 fusion (1/13, 7.7%) and MYB-FMO5 fusion (1/30, 3.3%) in OTSCC and ACC respectively, which might play a role in facilitating tumor progression. The data exhibited promising translational value as numerous actionable genes were identified with mutations. 76.9% OTSCC and 20% salivary ACC harbored at least one alteration in actionable genes, mutations in CDKN2A (4/13, 30.8%), NTRK3 (3/13, 23.1%) in OTSCC and FGFR2 (2/30, 6.7%), BRAF (2/30, 6.7%) in salivary gland ACC, suggesting targeted immunotherapy might be an effective intervention. Instead of MYB-independent NFIB fusions previously reported in ACC, only NFIB-independent MYB fusions were found in our cohort, indicating that alterations in NFIB rather than MYB might be essential to ACC tumorigenesis. Conclusions: This study reveals the genetic underpinnings of two rare malignancies in Chinese population, illustrating consistent mutational features with published literature as well as demonstrating several distinct genetic alterations, warranting further investigations. Citation Format: Ning Li, Shuhang Wang, Yue Yu, Yuan Fang, Huiyao Huang, Dawei Wu, Hong Fang, Chao Sun, Anqi Yu, Qi Fan, Shi-Yuan Cheng. Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-310.

The Relationship Between Single Nucleotide Polymorphisms of SMAD3/SMAD6 and Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

BackgroundThe TGF-β signal pathways play a key role in the development and promotion of squamous cell carcinoma (SCC). The pathway is mediated by the SMAD family proteins that include SMAD3 and SMAD6. Our study aimed to evaluate the relationship between single nucleotide polymorphism (SNP) of SMAD3/SMAD6 and susceptibility to esophageal squamous cell carcinoma (ESCC) in the Chinese population.Patients and MethodsThis was a hospital-based case–control study compromised of 1043 ESCC patients and 1315 non-cancer patients. Seven SMAD3/SMAD6 (rs8028147, rs3743343, rs3743342, rs8025774, rs8031440, rs803167, and rs34643453) SNPs were selected and used to evaluate their correlation with ESCC susceptibility. Genetic model tests, stratified analyses, linkage disequilibrium analyses, and haplotype analyses were performed in our study.ResultsParticipants with SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A or rs8031627 G>A had a significantly higher risk of ESCC. This was more evident in males, older patients (>63 years), smokers, and non-alcohol drinking participants. Linkage disequilibrium analyses further revealed that there were strong correlations between SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A, and rs8031627 G>A. In the same line, haplotype analyses revealed that SMAD3 ACCCGGSMAD6A and SMAD3AGCCGGSMAD6A were associated with less susceptibility to ESCC while SMAD3ATTTAASMAD6A was associated with a higher risk of ESCC.ConclusionSNPs of SMAD3 were related to higher susceptibility to ESCC. As such, they may contribute to the development of viable strategies for early diagnosis and treatment of ESCC. However, more detailed association mechanisms between SMAD3/SMAD6 SNPs and ESCC need further experiments to prove.

1012P - A multi-center integrative study on cancer predisposition genes in Chinese patients with epithelial ovarian carcinoma

BackgroundThe prevalence of BRCA1 and BRCA2 mutations varies among individual racial and ethnic groups. While, molecular epidemiological data on Chinese ovarian cancer patients is still insufficient. MethodsHere, we performed a multicenter study to investigate the clinical and molecular characteristics of 1,059 ovarian cancer patients. A hereditary cancer multigene panel including all NCCN recommended homologues recombination repair genes was performed. ResultsTotally, 1,059 patients with ovarian (n=982, 92.7%), fallopian tube (n=63, 5.9%) and peritoneal (n=14, 1.3%) cancer were recruited from 18 medical centers in China. 314 of 1,059 patients carried deleterious germline aberration in HRR genes including BRCA1 (19.1%), BRCA2 (6.5%) and other HRR genes (4.1%). Another 15 patients carried abnormality in MMR pathway as well as genes of other familial cancer syndrome like MUTYH, STK11, TP53. Histologically, BRCA1/2 mutations, in our study, were enriched not only in HGSC, but also in HGSC (P<0.001 for BRCA1, P=0.05 for BRCA2), which was seldomly investigated. Patients with germline BRCA1 mutations associated with early-onset (age≤50 years, P<0.001), higher chances of breast cancer (P<0.001), family history of HBOC (P<0.001) and relapse after initial treatment (P=0.068). Recurrent patients harbored more deleterious mutations than primary patients although the differences reached no significance in patients with HGSC subtype (P=0.056), suggesting a selection bias. Moreover, it is of our greatest interest that sensitivity to platinum-based therapy was largely depending on BRCA2 status (P=0.023 for all ovarian cancer, P=0.035 for HGSC). While, no significant association was found in BRCA1 mutated group (P=0.3). ConclusionsTo date, it is the largest study on predisposition genes in ovarian carcinoma in Chinese population. Our study disclosed a more complexed spectrum as well as higher rate of germline aberrations compared with previously published data. Etiologically, our data revealed a putative contribution of mutated BRCA1 gene to the onset of ovarian cancer with serous phenotype. Clinically, BRCA2 and other HRR and MMR genes may be used as useful predictive tools for Platinum sensitivity. Legal entity responsible for the studyBGI Genomics. FundingBGI genomics. DisclosureC. Zhu: Full / Part-time employment: BGI genomics. D. Shao: Full / Part-time employment: BGI genomics. All other authors have declared no conflicts of interest.

De-escalation Protocols in HPV-related Oropharyngeal Carcinoma in Chinese Populations

De-escalation Protocols in HPV-related Oropharyngeal Carcinoma in Chinese Populations

Several issues and prospects of poorly differentiated laryngeal squamous cell carcinoma in Chinese population

低分化喉鳞状细胞癌（鳞癌）作为喉癌的一种病理分化亚型，较高分化鳞癌少见但恶性程度高，预后差，更易发生局部和远处转移。但目前针对分化程度而制定诊疗建议尚未形成共识。因此，有必要对低分化喉鳞癌这一特殊群体进行更多基础及临床研究，探索更好的治疗方案，充分预测与分化相关的患者预后，指导个体化精准治疗，促进针对中国人群低分化喉鳞癌患者的治疗策略进步。.

Gastric cancer may share genetic predisposition with esophageal squamous cell carcinoma in Chinese populations.

Many features are shared between esophageal cancer (EC) and gastric cancer (GC). This study aimed to explore whether known EC susceptibility loci are also important in the development of GC. A total of 21 genetic variants associated with EC in genome-wide association studies were evaluated with association of GC risk in 2631 cases and 4373 controls of Chinese ancestry. Single variant and weighted genetic scores (WGS) for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and overall EC were analyzed with GC risk, respectively. Genetic variants of rs2274223 in PLCE1 at 10q23.33 (per G allele: odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.16-1.38, P = 6.51 × 10-8), rs10052657 in PDE4D at 5q11.2 (per C allele: OR = 1.12, 95% CI: 1.01-1.25, P = 3.28 × 10-2) and rs671 in ALDH2 at 12q24.12 (per A-allele: OR = 0.83, 95% CI: 0.75-0.91, P = 1.14 × 10-4) were significantly associated with GC risk. The combined effect of those three variants had stronger influence on GC risk (OR = 1.31, 95% CI: 1.19-1.44, P = 2.34 × 10-8). High WGS of ESCC was also associated with increased risk of GC (P = 5.52 × 10-4 as a continuous variable) (trend test P = 2.71 × 10-4), whereas no statistically significant associations were observed between the WGS of EAC and GC risk (P = 0.66 as a continuous variable) (trend test P = 0.70). ESCC rather than EAC may share genetic susceptibility with GC. Genetic variants at 10q23.33, 5q11.2, and 12q24.12 may be useful as biomarkers to identify individuals with high risk for both ESCC and GC.

Polymorphisms in lncRNA PTENP1 and the risk of oral squamous cell carcinoma in a Chinese population.

PTENP1, a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. The relationship between PTENP1 and susceptibility tumors is reported, while, an association of PTENP1 with the risk of oral squamous cell carcinoma (OSCC) in Chinese population is lacked. This research is designed to investigate the association of PTENP1 with susceptibility of OSCC. In this research, TaqMan technology was used to test genotype in 342 OSCC patients and 711 healthy controls, so as to analyze the association between PTENP1 polymorphisms (rs7853346 rs865005 and rs10971638) and susceptibility of oral squamous cell carcinoma. The results of this research showed that rs7853346 [Additive model: Adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.66-0.99] was related to the OSCC risk. It was not found that the other two sites were associated with the susceptibility of OSCC. This research indicated that rs7853346 is statistically correlated with the OSCC risk.

Anastomotic leakage after intrathoracic versus cervical oesophagogastric anastomosis for oesophageal carcinoma in Chinese population: a retrospective cohort study

ObjectiveTo investigate the characteristics and predictors for anastomotic leakage after oesophagectomy for oesophageal carcinoma from the perspective of anastomotic level.DesignRetrospective cohort study.SettingsA single tertiary medical centre in China.ParticipantsFrom January 2010...

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.