The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell ...activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).
Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis.
Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation-associated molecules were seen to be associated with the development of systemic non-CNS (central nervous system) NHL, but not with the development of primary CNS lymphoma.
Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies.
Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL.
Background
Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer globally. The development of squamous cell carcinoma has important inflammatory ...influences and effects. We, therefore, examined circulating levels of inflammation- and immune-related proteins for associations with ESCC.
Methods
We used pre-treatment EDTA plasma from 80 ESCC patients (44% clinical stages I and II) and 80 cancer-free control individuals within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 184 biomarkers were measured by high-throughput multiplexed proximity extension assays using Olink’s Proseek Cell Regulation and Immuno-Oncology Panels. ESCC odds ratios (OR) per quantile (based on two to four categories) of each biomarker were calculated by unconditional logistic regression models, adjusted for age, sex, cigarette smoking and alcohol consumption. Correlations among continuous biomarker levels were assessed by Spearman’s rank correlation. All statistical tests were two-sided with
p
values < 0.05 considered as significant. Given the exploratory nature of the study, we did not adjust for multiple comparisons.
Results
Seven proteins were undetectable in nearly all samples. Of the remaining 177 evaluable biomarkers, levels of cluster of differentiation 40 (CD40, per quartile OR 1.64;
p
trend = 0.018), syntaxin 16 (STX16, per quartile OR 1.63;
p
trend = 0.008), heme oxygenase 1 (per quartile OR 1.59;
p
trend = 0.014), and γ-secretase activating protein (GSAP, per quartile OR 1.47;
p
trend = 0.036) were significantly associated with ESCC. Amongst these significant markers, levels of CD40, STX16, and GSPA were moderately correlated (Rho coefficients 0.46–0.55;
p
< 0.05).
Conclusion
Our case–control study expands the range of inflammation and immune molecules associated with ESCC. These novel findings warrant replication and functional characterization.
This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric ...cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls.
A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer.
Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only.
These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.
Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated ...risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (Ptrends < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia.
Age-specific analyses of non-cardia gastric cancer incidence reveal divergent trends among US whites: rates are declining in individuals aged 40 years and older but rising in younger persons. To ...investigate this heterogeneity further, incidence trends were evaluated by anatomical subsite.
Gastric cancer incidence data for 1976-2007 were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the US Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change were calculated by age group (25-39, 40-59 and 60-84 years), race/ethnicity and subsite.
Based on data from the nine oldest SEER registries (covering ~10% of the US population), rates for all non-cardia subsites decreased in whites and blacks, except for corpus cancer, which increased between 1976 and 2007 with estimated annual percentage changes of 1.0% (95% CI 0.1% to 1.9%) for whites and 3.5% (95% CI 1.8% to 5.2%) for blacks. In contrast, rates for all non-cardia subsites including corpus cancer declined among other races. In combined data from NPCR and SEER registries (covering 89% of the US population), corpus cancer significantly increased between 1999 and 2007 among younger and middle-aged whites; in ethnic-specific analyses, rates significantly increased among the same age groups in non-Hispanic whites and were stable among Hispanic whites. Age-specific rates for all subsites declined or were stable in this period among blacks and other races.
Long- and short-term incidence trends for gastric cancers indicate a shifting distribution by anatomical subsite. Corpus cancer may have distinctive aetiology and changing risk factor exposures, warranting further investigation.
Incidence rates of non‐Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers ...of multiple viral infections in pre‐diagnostic blood and NHL risk in East Asians. We conducted a nested case‐control study of 214 NHL cases and 214 matched controls from three population‐based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead‐based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA‐D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10‐3.81; ptrend = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96‐4.89; ptrend = 0.008) Epstein‐Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus‐6 (HHV‐6) antigen (OR = 1.85, 95% CI = 1.04‐3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV‐HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV‐6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.
What's new?
Viral infections are among the strongest risk factors for non‐Hodgkin lymphoma (NHL), but the relationship between some individual viruses and NHL risk is still unclear. Here the authors provide a first prospective assessment of multiple viral markers and NHL risk in East Asians from three population‐based cohorts in China and Singapore. An increased risk was associated with antibodies against specific Epstein‐Barr virus, human herpesvirus‐6 and hepatitis B virus antigens, underscoring the association of NHL with viral infections.
Background & Aims: TLR4 is a cell-surface signaling receptor involved in the recognition and host response to Helicobacter pylori . The TLR4 +896A>G polymorphism linked with impaired reactivity to ...bacterial lipopolysaccharide may play a role in gastric carcinogenesis. Methods: We assessed associations with premalignant gastric changes in 149 relatives of gastric cancer patients, including 45 with hypochlorhydria and gastric atrophy. We also genotyped 2 independent Caucasian population-based case–control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors. Results: TLR4 +896G carriers had an 11-fold (95% confidence interval CI, 2.5–48) increased odds ratio (OR) for hypochlorhydria; the polymorphism was unassociated with gastric acid output in the absence of H pylori infection. Carriers also had significantly more severe gastric atrophy and inflammation. Seventeen percent of gastric carcinoma patients in the initial study and 15% of the noncardia gastric carcinoma patients in the replication study had 1 or 2 TLR4 variant alleles vs 8% of both control populations (combined OR = 2.3; 95% CI = 1.6–3.4). In contrast, prevalence of TLR4 +896G was not significantly increased in esophageal squamous cell (2%, OR = 0.2) or adenocarcinoma (9%, OR = 1.4) or gastric cardia carcinoma (11%, OR = 1.4). Conclusions: Our data suggest that the TLR4 +896A>G polymorphism is a risk factor for noncardia gastric carcinoma and its precursors. The findings underscore the role of the host innate immune response in outcome of H pylori infection.
PURPOSE HIV-infected persons have an elevated risk of developing non-Hodgkin's lymphoma (NHL); this risk remains increased in the era of effective HIV therapy. We evaluated serum immunoglobulin (Ig) ...proteins as predictors of NHL risk among HIV-infected individuals. PATIENTS AND METHODS By using three cohorts of HIV-infected persons (from 1982 to 2005), we identified 66 individuals who developed NHL and 225 matched (by cohort, sex, ethnicity, age, and CD4 count), HIV-infected, lymphoma-free controls who had available stored prediagnostic blood samples. Serum/plasma samples obtained 0 to 2 years and 2 to 5 years before diagnosis/selection were assayed for IgG, IgM, and IgA levels; monoclonal (M) Igs; and kappa and lambda free light chain (FLC) levels. Patients and matched controls were compared by using conditional logistic regression. Results The kappa and lambda FLCs were both significantly higher in patients (eg, in 2- to 5-year window: median kappa, 4.24 v 3.43 mg/dL; median lambda, 4.04 v 3.09 mg/dL) and strongly predicted NHL in a dose-response manner up to 2 to 5 years before diagnosis/selection (eg, NHL risk 3.76-fold higher with kappa concentration at least 2.00 times the upper limit of normal, and 8.13-fold higher with lambda concentration at least 2.00 times the upper limit of normal compared with normal levels). In contrast, IgG, IgM, and IgA levels were similar in patients and controls. M proteins were detected in only two patients with NHL (3%) and in nine controls (4%), and they were not significantly associated with NHL risk. CONCLUSION Elevated FLCs may represent sensitive markers of polyclonal B-cell activation and dysfunction and could be useful for identifying HIV-infected persons at increased NHL risk.
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