Browsing by Subject "Esophageal Neoplasms"

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    ItemOpen Access
    Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck.
    (BMC cancer, 2011-06-20) Ma, Hongxia; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, Qingyi
    Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN.We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population.Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend=0.046), particularly for non-oropharyngeal tumors (Ptrend=0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR=1.29, 95% CI=1.01-1.64; AG/GG vs. AA: adjusted OR=1.30, 95% CI=1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR=0.54, 95% CI=0.34-0.86; TG/GG vs. TT: adjusted OR=0.76, 95% CI=0.61-0.95).Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers.
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    Associations of PI3KR1 and mTOR polymorphisms with esophageal squamous cell carcinoma risk and gene-environment interactions in Eastern Chinese populations.
    (Scientific reports, 2015-01) Zhu, Jinhong; Wang, Mengyun; Zhu, Meiling; He, Jin; Wang, Jiu-Cun; Jin, Li; Wang, Xiao-Feng; Xiang, Jia-Qing; Wei, Qingyi
    Single nucleotide polymorphisms (SNPs) in the PI3K/PTEN/AKT/mTOR signaling pathway may contribute to carcinogenesis. We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk. We observed no association with ESCC risk for any of the selected SNPs. However, the combined analysis of these SNPs revealed that subjects with one-to-three risk genotypes had an increased ESCC risk. Stratified analysis by body mass index (BMI) found that ESCC risk was significantly associated with each of three mTOR SNPs among subjects with BMI < 25.0. Specifically, we found that subjects carrying ≥ 1 risk genotypes had significantly increased ESCC risk, particularly for males, ever-smokers, ever-drinkers, and those with age > 60, or BMI < 25.0. Moreover, three mTOR haplotypes were associated with an increase in ESCC risk. Our meta-analysis of mTOR rs2295080 and cancer risk provided further evidence that mTOR SNPs might modulate cancer susceptibility. In this population, such risk effects might be modified by other risk factors, highlighting the importance of gene-environment interaction in esophageal carcinogenesis. Additional, larger studies are warranted to validate our findings.
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    Does surgery improve outcomes for esophageal squamous cell carcinoma? An analysis using the surveillance epidemiology and end results registry from 1998 to 2008.
    (J Am Coll Surg, 2012-11) Worni, Mathias; Martin, Jeremiah; Gloor, Beat; Pietrobon, Ricardo; D'Amico, Thomas A; Akushevich, Igor; Berry, Mark F
    BACKGROUND: We examined survival associated with locally advanced esophageal squamous cell cancer (SCC) to evaluate if treatment without surgery could be considered adequate. STUDY DESIGN: Patients in the Surveillance, Epidemiology and End Results Registry (SEER) registry with stage II-III SCC of the mid or distal esophagus from 1998-2008 were grouped by treatment with definitive radiation versus esophagectomy with or without radiation. Information on chemotherapy is not recorded in SEER. Tumor stage was defined as first clinical tumor stage in case of neo-adjuvant therapy and pathological report if no neo-adjuvant therapy was performed. Cancer-specific (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier approach and propensity-score adjusted Cox proportional hazard models. RESULTS: Of the 2,431 patients analyzed, there were 844 stage IIA (34.7%), 428 stage IIB (17.6%), 1,159 stage III (47.7%) patients. Most were treated with definitive radiation (n = 1,426, 58.7%). Of the 1,005 (41.3%) patients who underwent surgery, 369 (36.7%) had preoperative radiation, 160 (15.9%) had postoperative radiation, and 476 (47.4%) had no radiation. Five-year survival was 17.9% for all patients, and 22.1%, 18.5%, and 14.5% for stages IIA, IIB, and stage III, respectively. Compared to treatment that included surgery, definitive radiation alone predicted worse propensity-score adjusted survival for all patients (CSS Hazard Ratio [HR] 1.48, p < 0.001; OS HR 1.46, p < 0.001) and for stage IIA, IIB, and III patients individually (all p values ≤ 0.01). Compared to surgery alone, surgery with radiation predicted improved survival for stage III patients (CSS HR 0.62, p = 0.001, OS HR 0.62, p < 0.001) but not stage IIA or IIB (all p values > 0.18). CONCLUSIONS: Esophagectomy is associated with improved survival for patients with locally advanced SCC and should be considered as an integral component of the treatment algorithm if feasible.
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    Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.
    (PLoS One, 2012) Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Lyerly, H Kim
    BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site.
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    Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.
    (Journal of translational medicine, 2016-05-31) Zhou, Fei; Zhu, Meiling; Wang, Mengyun; Qiu, Lixin; Cheng, Lei; Jia, Ming; Xiang, Jiaqing; Wei, Qingyi
    Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.
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    Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population.
    (Journal of cellular and molecular medicine, 2016-04) Zhu, Jinhong; Wang, Mengyun; He, Jing; Zhu, Meiling; Wang, Jiu-Cun; Jin, Li; Wang, Xiao-Feng; Yang, Ya-Jun; Xiang, Jia-Qing; Wei, Qingyi
    Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42-0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43-0.94) and non-drinkers (OR = 0.79, 95% CI = 0.64-0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37-0.83) and non-drinker (adjusted OR = 0.75, 95% CI = 0.60-0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene-gene interactions among three AKT1 SNPs (P < 0.015). A three-AKT1 SNP haplotype (C-A-C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52-0.94). Multifactor dimensionality reduction analysis confirmed a high-order gene-environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene-environment interplay in ESCC carcinogenesis.
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    Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma (ESCC) in Eastern Chinese populations.
    (PloS one, 2012-01) Zhu, Mei-Ling; Shi, Ting-Yan; Hu, Hai-Chuan; He, Jing; Wang, Mengyun; Jin, Li; Yang, Ya-Jun; Wang, Jiu-Cun; Sun, Meng-Hong; Chen, Huan; Zhao, Kuai-Le; Zhang, Zhen; Chen, Hai-Quan; Xiang, Jia-Qing; Wei, Qing-Yi
    BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies.
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    Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations.
    (Scientific reports, 2014-01) Zhu, Mei-Ling; He, Jing; Wang, MengYun; Sun, Meng-Hong; Jin, Li; Wang, Xiaofeng; Yang, Ya-Jun; Wang, Jiu-Cun; Zheng, Leizhen; Xiang, Jia-Qing; Wei, Qing-Yi
    ERCC2 is indispensable for nucleotide excision repair pathway, and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.30 and 1.24, 95% CI = 1.02-1.66 and 1.03-1.49 for TG and TG/TT, respectively, compared with GG), particularly in the subgroup of those smoked more than 16 pack-years. Multivariate logistic regression analysis suggested a possible multiplicative gene-environment interaction between rs238406 genotypes and smoking (Pinteraction = 0.026) on ESCC risk. Although no significant risk associations were observed for rs13181, further mini meta-analysis with our and 18 other published studies of 5,012 cases and 8,238 controls found evidence of an association between the rs13181 variant G allele and esophageal cancer risk (TG/GG vs. TT, OR = 1.17; 95% CI = 1.02-1.33). Interestingly, we consistently found a significant correlation between variant genotypes of these two SNPs and ERCC2 mRNA expression. These findings suggest that potentially functional SNPs in ERCC2 may contribute to ESCC risk.
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    Pri-miR-124 rs531564 and pri-miR-34b/c rs4938723 polymorphisms are associated with decreased risk of esophageal squamous cell carcinoma in Chinese populations.
    (PloS one, 2014-01) Zhang, Junjie; Huang, Xuewen; Xiao, Juanjuan; Yang, Yajun; Zhou, Yinghui; Wang, Xiaofeng; Liu, Qingmei; Yang, Jingmin; Wang, Mengyun; Qiu, Lixin; Zheng, Yabiao; Zhang, Ping; Li, Jin; Wang, Ya'nong; Wei, Qingyi; Jin, Li; Wang, Jiucun; Wang, Minghua
    MicroRNAs are a new class of small non-protein-coding RNAs that sometimes function as tumor suppressors or oncogenes. Aberrant expression and structural alteration of microRNAs have been reported to be involved in tumorigenesis and cancer development. Recently, rs531564/pri-miR-124-1, rs4938723/pri-miR-34b/c, rs7372209/pri-miR-26a-1, rs895819/pre-miR-27a, and rs11134527/pri-miR-218 were reported to be associated with risks of various cancers. In order to evaluate the relationship of these SNPs and esophageal squamous cell carcinoma (ESCC) risk, we conducted a case-control study with 1109 ESCC patients and 1275 control subjects to examine the potential association of these pri/pre-miRNA polymorphisms with ESCC susceptibility. As a result, two SNPs were associated with a significant risk of ESCC. We found that the GG genotype of pri-miR-124-1 rs531564 was associated to a significantly decreased risk of ESCC comparing with the CC/CG genotypes (p = 0.005; OR = 0.61, 95% CI = 0.43-0.86). In addition, the CC genotype of pri-miR-34b/c rs4938723 was associated with a significant decreased risk of ESCC (CC VS.p = 0.007, OR = 0.82, 95% CI = 0.71-0.95) in Chinese population. The present study provides the first evidence that pri-miR-124-1 rs531564 and pri-miR-34 rs4938723 were associated with the risk of ESCC in Chinese population.
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    Underlying mechanisms of change in cancer prevalence in older U.S. adults: contributions of incidence, survival, and ascertainment at early stages.
    (Cancer causes & control : CCC, 2022-09) Akushevich, I; Yashkin, A; Kovtun, M; Yashin, AI; Kravchenko, J

    Purpose

    To quantitatively evaluate contributions of trends in incidence, relative survival, and stage at diagnosis to the dynamics in the prevalence of major cancers (lung, prostate, colon, breast, urinary bladder, ovaries, stomach, pancreas, esophagus, kidney, liver, and skin melanoma) among older U.S. adults age 65 +.

    Methods

    Trend partitioning was applied to the Surveillance, Epidemiology, and End Results Program data for 1973-2016.

    Results

    Growth of cancer prevalence in older adults decelerated or even decreased over time for all studied cancers due to decreasing incidence and improving survival for most of cancers, with a smaller contribution of the stage at cancer diagnosis. Changes in the prevalence of cancers of the lung, colon, stomach, and breast were predominantly due to decreasing incidence, increasing survival and more frequent diagnoses at earlier stages. Changes in prevalence of some other cancers demonstrated adverse trends such as decreasing survival in localized and regional stages (urinary bladder and ovarian) and growing impact of late-stage diagnoses (esophageal cancer).

    Conclusion

    While decelerating or decreasing prevalence of many cancers were due to a beneficial combination of decreasing incidence and increasing survival, there are cancers for which decelerating prevalence is due to lack of improvement in their stage-specific survival and/or increasing frequency of diagnosis at advanced stages. Overall, if the observed trends persist, it is likely that the burden associated with cancer prevalence in older U.S. adults will be lower  comparing to projections based on constant increasing prevalence have previously estimated.