ORCID Profile
0000-0001-9871-0809
Current Organisation
Yale University Yale School of Public Health
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Publisher: American Association for Cancer Research (AACR)
Date: 2021
DOI: 10.1158/1055-9965.EPI-20-0739
Abstract: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni & 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P & 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger s le sets are required to confirm our findings.
Publisher: Wiley
Date: 17-11-2020
DOI: 10.1002/IJC.33360
Abstract: A full‐term pregnancy is associated with reduced endometrial cancer risk however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy‐related factors and endometrial cancer risk are less clear. We pooled in idual participant data from 11 cohort and 19 case‐control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one‐ and two‐stage meta‐analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full‐term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full‐term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56‐0.63). The risk reduction appeared the greatest for the first full‐term pregnancy (OR = 0.78, 95% CI 0.72‐0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14‐0.28) that was independent of age at last full‐term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%‐9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full‐term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full‐term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2018
DOI: 10.1038/S41467-018-05427-7
Abstract: Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins ( SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 08-02-2018
DOI: 10.1038/S41467-018-02942-5
Abstract: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/ TNS3 , P = 4.35 × 10 −8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 ( NOC2L , P = 8.36 × 10 −14 ), rs2941471 at 8q21.11 ( HNF4G , P = 6.60 × 10 −10 ), rs4795218 at 17q12 ( HNF1B , P = 1.32 × 10 −8 ), and rs1517037 at 18q21.32 ( GRP , P = 3.28 × 10 −8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
Publisher: Wiley
Date: 07-08-2020
DOI: 10.1002/IJC.33206
Publisher: Elsevier BV
Date: 03-2023
Location: United States of America
No related grants have been discovered for Lingeng Lu.