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  • American Association for Cancer Research (AACR)  (8)
  • Li, Donghui  (8)
  • Medicine  (8)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 6 ( 2006-03-15), p. 3323-3330
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 6 ( 2006-03-15), p. 3323-3330
    Abstract: Genetic variation in DNA repair may affect the clinical response to cytotoxic therapies. We investigated the effect of six single nucleotide polymorphisms of the RecQ1, RAD54L, XRCC2, and XRCC3 genes on overall survival of 378 patients with pancreatic adenocarcinoma who were treated at University of Texas M.D. Anderson Cancer Center during February 1999 to October 2004 and were followed up to October 2005. Genotypes were determined using the MassCode method. Survival was determined from pathologic diagnosis to death. Patients who were alive at the last follow-up evaluation were censored at that time. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare overall survival by genotypes. A significant effect on survival of all patients was observed for RecQ1 and RAD54L genes. The median survival time was 19.2, 14.7, and 13.2 months for the RecQ1 159 AA, AC, and CC genotypes, and 16.4, 13.3, and 10.3 months for RAD54L 157 CC, CT, and TT genotypes, respectively. A significantly reduced survival was associated with the variant alleles of XRCC2 R188H and XRCC3 A17893G in subgroup analysis. When the four genes were analyzed in combination, an increasing number of adverse alleles were associated with a significantly decreased survival. Subgroup analyses have shown that the genotype effect on survival was present among patients without metastatic disease or among patients who receive radiotherapy. These observations suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly affect the clinical outcome of patients with pancreatic cancer. (Cancer Res 2006; 66(6): 3323-30)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3750-3750
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3750-3750
    Abstract: Background: There is accumulating evidence that obesity and diabetes are modifiable risk factors for pancreatic cancer. However, the genetic factors predispose individuals with obesity or diabetes to pancreatic cancer has not been identified. Aims: To investigate the hypothesis that obesity- and diabetes-related genes modify the risk of pancreatic cancer. Methods: We genotyped 15 single nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO), peroxisome proliferators-activated receptor gamma (PPARγ), nuclear receptor family 5 member 2 NR5A2 (aka liver receptor homolog 1), AMP-activated protein kinase (AMPK), and adiponectin (ADIPOQ) gene in 1,070 patients with pancreatic cancer and 1,175 cancer-free controls that are enrolled in a case control study conducted at MD Anderson Cancer Center during 2000-2008. Information on risk factors was collected by personal interview. Genotypes were determined using the Taqman method. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using multivariable unconditional logistic regression. Results: The PPARγ P12A (rs1801282) GG genotype was inversely associated with risk of pancreatic cancer (AOR: 0.21, 95%CI: 0.07−0.62). Three NR5A2 variants (rs12029406, rs3790844 and rs3790843) that were previously identified in a genome-wide association study were significantly associated with reduced risk of pancreatic cancer, AORs ranging 0.57-0.79. Two FTO gene variants (rs8050136 and rs9939609) and one ADIPOQ variant (rs17366743) were differentially associated with pancreatic cancer according to levels of body mass index (BMI) (P interaction = 0.0001, 0.0015, and 0.03). The variant alleles were associated reduced risk of pancreatic cancer among individuals with normal weight but increased risk among those with excess body weight. For example, the AOR (95%CI) for FTO IVS1-2777 AC/AA genotype (rs8050136) was 0.72 (0.55-0.96) and 1.54 (1.14-2.09) in participants with a BMI & lt;25 or ≥ 25 kg/m2, respectively. We observed no significant association between AMPK genotype and pancreatic cancer and no genotype interactions with diabetes or smoking. Conclusion: Our findings suggest a protective effect of PPARγ P12A GG genotype and NR5A2 variants on pancreatic cancer. A positive association of FTO and ADIPOQ gene variants with pancreatic cancer may be limited to persons who are overweight. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3750. doi:10.1158/1538-7445.AM2011-3750
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 18 ( 2020-09-15), p. 4004-4013
    Abstract: Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values & lt; 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. Significance: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3594-3594
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3594-3594
    Abstract: Concurrent with the increase in hepatocellular carcinoma (HCC) incidence, the prevalence of metabolic syndrome has increased in the USA. Metabolic syndrome is currently considered a major health problem. Moreover, long term diabetes mellitus is an independent risk factor for HCC. We have previously shown that use of metformin among diabetics was associated with 70% risk reduction of HCC as compare to the use of other types of antidiabetic treatment. It is not known, however, if diabetic patients with HCC who used metformin had a better prognosis. Between 2001 and 2010 we interviewed 438 patients with pathologically confirmed HCC for multiple risk factors of HCC including prior history of diabetes and type of antidiabetic treatment. Survival times were calculated from the date of pathology diagnosis and were censored for patients who were alive at the last follow up. Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model (CPHM) was used to estimate the multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Total of 130 HCC patients (29.7%) recalled prior history of diabetes with more than 1 year prior to HCC diagnosis. Most subjects were considered to have type 2 diabetes mellitus and were on an oral antidiabetic regimen. The survival duration for HCC patients with diabetes did not significantly differs from those without diabetes in men and women. However, HCC diabetic men who received metformin had a better survival outcome. The median survival was 14.9 months (95% CI, 1.3-28.9) for metformin users compared to 12.7 months (95% CI. 6.2-10.1) among HCC diabetic men who received other treatments, Log Rank p value=.04. CPHM, which included age, hepatitis C virus infection, alcohol consumption, treatment of HCC (chemotherapy and surgical treatment), history of cirrhosis, and Liver Italian Program (CLIP) staging score yielded 40% improvement of overall survival in HCC men with diabetes who received metformin as compared to other treatments. The estimated HRR (95% CI) was 0.56 (.35-.91), P =.02. These results suggest a possible beneficial role of metformin in diabetic men with HCC. Such observations need to be confirmed in other populations and with correlation with duration of metformin intake. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3594. doi:1538-7445.AM2012-3594
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 5
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    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Clinical Cancer Research Vol. 18, No. 10 ( 2012-05-15), p. 2905-2912
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 18, No. 10 ( 2012-05-15), p. 2905-2912
    Abstract: Purpose: Accumulating evidence suggests that metformin has antitumor activity. The aim of this study was to determine whether metformin use has a survival benefit in patients with pancreatic cancer. Experimental Design: We conducted a retrospective study of patients with diabetes and pancreatic cancer treated at The University of Texas MD Anderson Cancer Center (Houston, TX). Information on diabetes history, including treatment modalities and clinical outcome of pancreatic cancer, was collected using personal interviews and medical record review. Survival analysis was carried out using a Kaplan–Meier plot, log-rank test, and Cox proportional hazards regression models. Results: Among the 302 patients identified, there were no significant differences in demographic or major clinical characteristics between the patients who had received metformin (n = 117) and those who had not (n = 185). The 2-year survival rate was 30.1% for the metformin group and 15.4% for the non-metformin group (P = 0.004; χ2 test). The median overall survival time was 15.2 months for the metformin group, and 11.1 months for the non-metformin group (P = 0.004, log-rank test). Metformin users had a 32% lower risk of death; the HR (95% confidence interval) was 0.68 (0.52–0.89) in a univariate model (P = 0.004), 0.64 (0.48–0.86) after adjusting for other clinical predictors (P = 0.003), and 0.62 (0.44–0.87) after excluding insulin users (P = 0.006). Metformin use was significantly associated with longer survival in patients with nonmetastatic disease only. Conclusions: Our finding that metformin use was associated with improved outcome of patients with diabetes and pancreatic cancer should be confirmed in independent studies. Future research should prospectively evaluate metformin as a supplemental therapy in this population. Clin Cancer Res; 18(10); 2905–12. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 11 ( 2021-06-01), p. 3134-3143
    Abstract: Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P & lt; 5 × 10–8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82–0.93; former smokers 1.00, 95% CI, 0.91–1.07; current smokers 1.25, 95% CI 1.12–1.40, Pinteraction = 3.08 × 10–9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. Significance: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 5046-5046
    Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver with a five-year survival rate of less than 5 percent. Gallbladder disease (GBD) is defined as the presence of cholelithiasis or cholecystitis. Both cholelithiasis and cholecystitis have been reported as risk factors in the development of gastrointestinal cancers, such as biliary tract and pancreatic cancers. Moreover, patients with GBD tend to develop chronic liver diseases, which may progress to cirrhosis. However, the role of GBD in the development of non-cirrhotic related HCC has not been elucidated. We aimed to investigate the role of GBD and the risk of HCC development in the absence of cirrhosis. METHODS: We conducted a case-control study at The University of Texas M.D. Anderson Cancer Center. Cases were defined as pathologically confirmed HCC. Controls were healthy individuals without prior history of cancer, who were spouses of other cancer patients seen at MD Anderson. All subjects were USA residents. Participants were personally interviewed for prior history of GBD and for several HCC risk factors (environmental, behavioral, chronic medical conditions, and family history of cancer). Blood samples of all participants were tested for markers of hepatitis B and C viruses. We reviewed the pathology and radiology records of HCC patients to assess presence and absence of cirrhosis. Multivariable logistic regression analysis was conducted to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for the association between GBD and HCC in the absence of cirrhosis and with adjustment for potential confounders. RESULTS: Between 2000 and 2017, a total of 1333 cases and 1104 controls were enrolled in the study. After review, 347 HCC case patients showed no evidence of cirrhosis and were eligible for this analysis. The prevalence of GBD based on the participants’ recall during personal interview was 22.7% in the cases. Upon further assessment by review of medical records, the prevalence of GBD was 40.3% in the cases. Individuals with GBD were two times more likely to develop HCC than individuals with no history of GBD (AOR = 2.0; 95% CI: 1.4 – 2.8). The estimated AOR did not meaningfully change when we rely on the prevalence of GBD recalled by cases (22.7%) versus prevalence of GBD obtained from medical records (40.3%). The association between GBD and HCC continue to be significant in the absence of viral hepatitis, through a restricted analysis among non-viral non-cirrhotic population after controlling for age, sex race, alcohol use, cigarette smoking, diabetes mellitus, and family history of cancer. CONCLUSIONS: We conclude that GBD is a significant risk factor for HCC development in absence of cirrhosis. Future research aiming at investigating the underlying mechanism of GBD-induced HCC in absence of cirrhosis should be warranted. In addition, patients with GBD should be screened for evidence of cirrhosis. Citation Format: Kenda Al-Assi, Rikita Hatia, Vijayashri Rallapalli, Yehia I. Abugabal, Ahmed Abdelhakeem, Reham Abdel-Wahab, Kanwal Raghav, Prasun K. Jalal, Ahmed Kaseb, Asif Rashid, Donghui Li, Manal Hassan. Gallbladder disease and the risk of hepatocellular carcinoma: US case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5046.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3282-3282
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3282-3282
    Abstract: Background: We aimed to categorize the most common comorbid medical conditions in pancreatic cancer (PC) patients and to determine whether these conditions have impact on the overall survival (OS). Methods: Between January 2000 and 2014, 2165 patients with pathologically confirmed adenocarcinoma of the pancreas consented to participate in a clinico-epidemiological study at the University of Texas MD Anderson Cancer Center. We reviewed the electronic medical records of all patients to identify the prevalence of four chronic medical conditions, including systemic hypertension, hyperlipidemia, type 2 diabetes, and altered morphology of the pancreas. Prevalence of each chronic disease was assessed and median survival was estimated by using the Kaplan-Meier product-limit method, and significant differences between the survival times were determined by using the log-rank test. Results: Among all patients, 950 (43.9%) had history of hypertension, 516 (23.8%) had hyperlipidemia, 585 (27%) had type 2 diabetes. Radiological and pathological records indicted presence of steatosis (0.4%), fibrosis (1.9%), and pancreatitis (9.9%). The prevalence of hyperlipidemia and diabetes was significantly higher in men (27.9%, 30.2%) than in women (18.2%, 22.8%) respectively; P value & lt;.01. We found no significant variation in the prevalence of hypertension and altered pancreatic morphology between men and women. Hypertension was more frequent among African American patients while diabetes was more common among Hispanics and African Americans. No significant variations in the distribution of other conditions by ethnicity. Median survivals of PC patients by comorbidities are presented in table 1. Conclusion: Chronic medical conditions are commonly reported by PC patients and the prevalence of these conditions may vary by gender. However, the impact of these conditions may not significantly affect the survival of the patients. The interaction treatment choices with these conditions still needs to be elaborated in future studies. OS (months), 95%CI of PC patients by comorbiditiesComorbidityYesNoP valueHypertension10.9 (10-11.7)11.6 (10.7-12.4).09Hyperlipidemia12 (11.8-13.1)10.9 (10.2-11.6).4Diabetes Mellitus9.7 (8.4-11.1)11.4 (10.7-12.1).1 Note: This abstract was not presented at the meeting. Citation Format: Ahmed O. Abousamra, David Fogelman, Vijayashri Rallapalli, Akram Shalaby, Milind Javle, Renato Lenzi, Linus Ho, Donghui Li, Manal Hassan. Common chronic medical conditions in pancreatic cancer: impact on overall survival [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3282. doi:10.1158/1538-7445.AM2017-3282
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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