Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium

Cook, Michael B.; Barnett, Matthew J; Bock, Cathryn H.; Cross, Amanda J.; Goodman, Phyllis J.; Goodman, Gary E.; Haiman, Christopher A.; Khaw, Kay‐Tee; McCullough, Marjorie L.; Newton, Christine C; Boutron‐Ruault, Marie‐Christine; Lund, Eiliv; Rutegård, Martin; Thornquist, Mark; Spriggs, Michael; Giffen, Carol; Freedman, Neal D.; Kemp, Troy J.; Kroenke, Candyce H.; Marchand, Loı̈c Le; Park, Jin Young; Simon, Michael S.; Wilkens, Lynne R.; Pinto, Lígia A.; Hildesheim, Allan; Campbell, Peter T.

doi:10.1136/gutjnl-2018-316678

Cited by 26 publications

(25 citation statements)

References 52 publications

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“…The multicohort study by Cook et al . using the above mentioned Luminex bead‐based assay (with 31 overlapping biomarkers) shared no significant associations with our study . These results further support the major etiologic differences between the two histologic subtypes.…”

Section: Discussionmentioning

confidence: 99%

Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case–cohort study in Japan

Aversa

Song

Shimazu³

et al. 2019

Intl Journal of Cancer

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Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer worldwide. Measurements of circulating inflammation-related biomarkers may inform etiology or provide noninvasive signatures for early diagnosis. We therefore examined levels of inflammation molecules for associations with ESCC risk. Using a case-cohort study designed within the Japan Public Health Center-based Prospective Study, we measured baseline plasma levels of 92 biomarkers using a multiplex assay in a subcohort of 410 randomly selected participants and 66 participants with incident ESCC (including four cases that occurred in the subcohort). ESCC hazard ratios (HRs) were calculated for 2-4 quantiles of each biomarker by Cox proportional hazards regression models with age as the time metric, adjusted for sex, smoking and alcohol use. Twenty analytes were undetectable in nearly all samples. Of the remaining 72, 12 biomarkers (FGF19, ST1A1, STAMBP, AXIN1, CASP8, NT3, CD6, CDCP1, CD5, SLAMF1, OPG and CSF1) were associated with increased ESCC risk (p trend < 0.05) with HRs per quantile 1.28-1.65. Seven biomarkers (CXCL6, CCL23, CXCL5, TGFA, CXCL1, OSM and CCL4) were inversely associated with HRs 0.57-0.72. FGF19, CASP8, STAMBP, ST1A1 and CCL-4 met statistical significance with false discovery rate correction. Associations did not differ <5 vs. ≥5 years between blood collection and ESCC diagnosis. CASP8, STAMBP and ST1A1 were strongly correlated (p < 0.05). Our study expands the range of inflammation molecules associated with the development of this highly lethal neoplasia. Correlations among these novel biomarkers suggest a possible shared pathway. These findings need replication and could further delineate ESCCs molecular mechanisms of carcinogenesis.Additional Supporting Information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case–cohort study in Japan

Aversa

Song

Shimazu³

et al. 2019

Intl Journal of Cancer

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“…Whereas, other studies revealed that IL-17A can enhance the tumor killing capability via humoral cell-mediated induction of immunogenic antibody and cytolytic molecules in ESCC [52]. Though, the role of circulating IL-17 or IL-22 in esophageal cancers is not yet defined [36] and further studies are needed to clarify the role of IL-17A and IL-22 in EACs.…”

Section: Plos Onementioning

confidence: 94%

“…A general limitation in analyzing systemic interleukins lies in the high number of confounding factors potentially influencing systemic interleukin levels. For example, Cook et al recently described a potential link between excessive obesity and cigarette smoking with systemic inflammation [36]. Also, other environmental factors like alcohol or the composition of the microbiota might alter systemic inflammation.…”

Section: Plos Onementioning

confidence: 99%

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Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas

et al. 2020

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Introduction Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies are diagnosis of EACs at an already advanced stage and distant metastases. Hence, we wanted to investigate the presence of systemic inflammatory interleukins (IL) and their impact on patient prognosis. Material and methods Systemic expression levels of pro-and anti-inflammatory markers (IL-2, IL-4, IL-6, IL-10, IL-17A and IL-22) in the sera of 43 EAC patients without neoadjuvant radiochemotherapy were measured by flow cytometric analysis. A correlation to clinicopathological data was performed. Log-rank and Cox regression analysis were used to investigate the impact on patient survival. 43 sera of age and gender matched healthy volunteers were used as controls. Results Increased systemic IL-6 (p = 0.044) and lower IL-17A (p = 0.002) levels were found in EAC patients as opposed to controls. A correlation of IL-10 levels with an increased T stage was found (p = 0.020). Also, systemic IL-10 levels were highly elevated in patients with distant metastasis (p<0.001). However, only systemic IL-17A levels had an influence on patient survival in multivariate analysis.

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“…Additionally, in our recent study of 2 US cohort studies, we reported that overweight in early adulthood and weight gain in later life were associated with increased EA and GCA risk . Although the underlying mechanisms of the BMI‐EA/GCA association are unclear, leading hypotheses include mediation by gastroesophageal reflux or metabolic dysfunction .…”

Section: Introductionmentioning

confidence: 98%

Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk

Petrick

Jensen

Sørensen

et al. 2019

Obesity

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Objective Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear. Methods This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7‐13 years) and early adulthood (17‐26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. Results The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50‐4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57‐6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood. Conclusions Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.

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Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium

Cited by 26 publications

References 52 publications

Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case–cohort study in Japan

Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case–cohort study in Japan

Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas

Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk

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