A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. METHODS: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. RESULTS: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend  = .02). CONCLUSION: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.

Soluble CD137 and risk of hepatocellular carcinoma: nested case-control studies in cohorts in Shanghai and Singapore.

BACKGROUND: The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment. METHODS: CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case-control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS). Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with levels of five cytokines-soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1ß), and tumour necrosis factor alpha (TNF-α). RESULTS: sCD137 levels were significantly higher in HCC cases than controls in both cohorts (Ps < 0.001). Compared with the lowest quartile, multivariable-adjusted ORs (95% CI) of HCC for the highest sCD137 quartile were 3.79 (1.73, 8.30) in the SCS and 3.49 (1.44, 8.48) in the SCHS. The sCD137-HCC association was independent of hepatitis B seropositivity and follow-up time. No other cytokine was consistently associated with HCC risk. CONCLUSION: sCD137 was associated with higher risk of HCC in two studies nested in general population cohorts. sCD137 may be a long-term risk marker of HCC development.

Composite dietary antioxidant index and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study.

Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer-free participants aged 45 to 74 years at baseline, a food-based CDAI was calculated according to a previously established and validated method that included six food-sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow-up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83-1.07), 0.86 (0.75-1.00) and 0.80 (0.66-0.98), respectively, compared to the lowest quartile (Ptrend  = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI-CRC risk association reached statistical significance. Our findings suggest that food-based antioxidants may be beneficial for reducing the risk of CRC in the general population.

Adherence to colonoscopy in cascade screening of colorectal cancer: A systematic review and meta-analysis.

BACKGROUND AND AIM: This study aims to systematically evaluate adherence to colonoscopy and related factors in cascade screening of colorectal cancer (CRC) among average-risk populations, which is crucial to achieve the effectiveness of CRC screening. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for studies published in English up to October 16, 2020, and reporting the adherence to colonoscopy following positive results of initial screening tests. A random-effects meta-analysis was applied to estimate pooled adherence and 95% confidence intervals. Subgroup analysis and mixed-effects meta-regression analysis were performed to evaluate heterogeneous factors for adherence level. RESULTS: A total of 245 observational and 97 experimental studies were included and generated a pooled adherence to colonoscopy of 76.6% (95% confidence interval: 74.1-78.9) and 80.4% (95% confidence interval: 77.2-83.1), respectively. The adherence varied substantially by calendar year of screening, continents, CRC incidence, socioeconomic status, recruitment methods, and type of initial screening tests, with the initial tests as the most modifiable heterogeneous factor for adherence across both observational (Q = 162.6, P < 0.001) and experimental studies (Q = 23.2, P < 0.001). The adherence to colonoscopy was at the highest level when using flexible sigmoidoscopy as an initial test, followed by using guaiac fecal occult blood test, quantitative or qualitative fecal immunochemical test, and risk assessment. The pooled estimate of adherence was positively associated with specificity and positive predictive value of initial screening tests, but negatively with sensitivity and positivity rate. CONCLUSIONS: Colonoscopy adherence is at a low level and differs by study-level characteristics of programs and populations. Initial screening tests with high specificity or positive predictive value may be followed by a high adherence to colonoscopy.

Findings from the first colorectal cancer screening among 103 542 individuals in Vietnam with systematic review of colorectal cancer screening programs in Asia-Pacific region.

BACKGROUND: Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam. METHODS: Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40 years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases. RESULTS: During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for immunochemical-fecal occult blood testing test was 11.9%. Among 2278 individuals who underwent colonoscopy, 3.5% were histologically diagnosed with cancer, 17.8% with advanced adenomas, and 23.1% with non-advanced adenomas. Males had significantly higher detection rate of advanced adenomas, cancer or ≥ two polyps/tumor than females (P < 0.0001). The systematic review showed that in two-step modality (i.e. immunochemical-fecal occult blood testing/fecal immunochemical test and colonoscopy), the test positive was from 4.1 to 10.6%. Once colonoscopy was performed subsequently, the rate of cancer among positive participants was from 1.7 to 16.4% and that of advanced adenomas was from 7.1 to 23.1%. CONCLUSION: We showed that the two-step modality is a promising strategy for colorectal cancer screening in Vietnam that might apply to similar settings with limited resources.

A global view of adherence to colonoscopy follow-up in cascade screening of colorectal cancer.

OBJECTIVE: To overview the colonoscopy adherence in cascade screening of colorectal cancer (CRC) and evaluate potential influence of the initial tests based on an ecological evaluation. METHODS: The performance of the initial screening tests and adherence to subsequent colonoscopy were extracted from relevant studies published up to 16 October 2020. The age-standardised incidence (ASRi) of CRC in populations in the year of screening was derived from the Cancer Statistics. RESULTS: One hundred sixty-six observational studies and 60 experimental studies were identified. Most studies applied cascade screening with faecal occult blood tests (FOBTs) as an initial test. The adherence to colonoscopy varied greatly across populations by continents, gross national income and type of initial tests, with a median (interquartile range) of 79.8% (63.1%-87.8%) in observational studies and 82.1% (66.7%-90.4%) in randomised trials. The adherence was positively correlated with the ASRi of CRC (r = 0.145, p = 0.023) and positive predictive value (PPV) of the initial tests (r = 0.206, p = 0.002) in observational studies and correlated with ASRi of CRC (r = 0.309, p = 0.002) and sensitivity of the initial tests (r = -0.704, p = 0.003) in experimental studies. CONCLUSIONS: Adherence to colonoscopy varies greatly across populations and is related with performance of the initial tests, indicating the importance to select appropriate initial tests.

Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults: Singapore Chinese Health Study.

Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of the Asian population. Relative telomere lengths in genomic DNA from peripheral blood samples were quantified using a validated quantitative real-time PCR among 26 540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer and deaths by quintiles of telomere length were calculated using the Cox proportional hazards regression method with adjustment for age, sex and other potential confounders. After baseline blood collection, 4353 persons developed cancer and 7609 died. Participants with the longest decile of telomeres had a 26% (95% CI: 11%-44%) higher risk of total cancer incidence compared to the shortest decile after controlling for age, sex and other potential founders (Ptrend < .0001). In contrast, longer telomeres were associated with lower risk of all-cause mortality (HR = 0.93; 95% CI: 0.84-1.03), noncancer death (HR = 0.81; 95% CI: 0.71-0.92), specifically, death from chronic obstructive pulmonary disease and pneumonia (HR = 0.79, 95% CI: 0.70-0.89) and digestive diseases (HR = 0.60, 95% CI: 0.42-0.88). Our findings demonstrated that longer telomeres are associated with increased risk of cancer development overall and several common cancer types including breast, rectal, prostate, pancreatic cancer and lung adenocarcinoma. Our study also confirmed that longer telomeres are associated with a reduced risk of noncancer related death.

Dietary fatty acids and colorectal cancer risk in men: A report from the Shanghai Men's Health Study and a meta-analysis.

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; Ptrend = 0.47) for SFA, 0.95 (0.79-1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95-1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.

Quality diet indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study.

There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.

Association between body mass index and colorectal adenomas: Findings from a case-control study in Vietnam.

Colorectal cancer is a leading cancer worldwide and in Vietnam. Adenomas (adenomatous polyps) is an important precursor of colorectal cancer. There is currently no study to determine the modifiable risk factors for colorectal adenomas, including body mass index (BMI) in Vietnam. We conducted an individually matched case-control study of 1149 colorectal adenomas and 1145 controls in a large-scale colorectal screening program involving 103 542 individuals aged 40-75 years old in Hanoi, Vietnam. Conditional logistic regression was used to evaluate the association between BMI and colorectal adenomas prevalence, after controlling for potential confounders. Overall, comparing to normal weight (ie, 18.5-22.9 kg/m2 ), underweight (ie, BMI < 18.5) was associated with a non-statistically significant increased prevalence of colorectal adenomas (odd ratio [OR] = 1.29 and 95% confident interval [CI]: 0.88-1.87). This association became significant among male (OR = 1.98, 95% CI: 1.20-3.27), male who were ever smokers (OR = 2.59, 95% CI: 1.33-5.03), nonregular exercise (OR = 2.44, 95% CI: 1.26-4.73) and individuals with cardiometabolic disorders (OR = 3.46, 95% CI: 1.19-10.00). The association between underweight and colorectal adenomas did not vary by smoking status, drinking status, family history of cancer, adenomas types or cardiometabolic disorders. No association was observed among obese individuals (BMI ≥ 25). In the population with low prevalence of obesity, we found that the association between BMI and colorectal adenomas followed a reversed J-shape that underweight was associated with increased prevalence. Further studies are, therefore, warranted to replicate our results and to investigate the biologic mechanism the effect of underweight on colorectal adenomas prevalence.

A prospective evaluation of serum methionine-related metabolites in relation to pancreatic cancer risk in two prospective cohort studies.

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73) and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16) and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.

PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma. METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies. RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98). CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.

A prospective study of dietary polyunsaturated fatty acids intake and lung cancer risk.

Animal studies have shown that polyunsaturated fatty acids (PUFAs) have antineoplastic and anti-inflammatory properties. Results from epidemiologic studies on specific types of PUFAs for lung cancer risk, however, are inconclusive. We prospectively evaluated the association of specific types of dietary PUFA intakes and lung cancer risk in two population-based cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS) with a total of 121,970 study participants (i.e., 65,076 women and 56,894 men). Dietary fatty acid intakes were derived from data collected at the baseline using validated food frequency questionnaires (FFQs). Cox proportional hazards model was performed to assess the association between PUFAs and lung cancer risk. Total, saturated and monounsaturated fatty acid intakes were not significantly associated with lung cancer risk. Total PUFAs intake was inversely associated with lung cancer risk [HRs and respective 95% CIs for quintiles 2-5 vs quintile 1: 0.84 (0.71-0.98), 0.97 (0.83-1.13), 0.86 (0.74-1.01) and 0.85 (0.73-1.00), ptrend  = 0.11]. However, DHA intake was positively associated with lung cancer risk [HRs and 95% CIs: 1.01 (0.86-1.19), 1.20 (1.03-1.41), 1.21 (1.03-1.42) and 1.24 (1.05-1.47), ptrend  = 0.001]. The ratio of n-6 PUFAs to n-3 PUFAs (i.e., 7:1) was inversely associated with lung cancer risk, particularly among never-smokers and adenocarcinoma patients. Total PUFAs and the ratio between n-6 PUFAs and n-3 PUFAs were inversely associated with lung cancer risk. This study highlights an important public health impact of PUFA intakes toward intervention/prevention programs of lung cancer.

Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium.

AIMS/HYPOTHESIS: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. METHODS: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. RESULTS: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. CONCLUSIONS/INTERPRETATION: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.

Survival predictors of Burkitt's lymphoma in children, adults and elderly in the United States during 2000-2013.

Burkitt's Lymphoma (BL) has three peaks of occurrence, in children, adults and elderly, at 10, 40 and 70 years respectively. To the best of our knowledge, no study has been conducted to assess predictors of survival in the three age groups. We hypothesized that survival predictors may differ by age group. We, therefore, sought to determine survival predictors for BL in these three groups: children (<15 years of age), adults (40-70 years of age) and elderly (>70 years of age). Using the Surveillance, Epidemiology, and End Results (SEER) database covering the years 2000-2013, we identified 797 children, 1,994 adults and 757 elderly patients newly diagnosed with BL. We used adjusted Cox proportional hazards regression models to determine prognostic factors for survival for each age group. Five-year relative survival in BL for children, adults and elderly were 90.4, 47.8 and 28.9%, respectively. Having at least Stage II disease and multiple primaries were associated with higher mortality in the elderly group. In adults, multiple primaries, Stage III or IV disease, African American race and bone marrow primary were associated with increased mortality whereas Stage IV disease and multiple primaries were associated with worse outcome in children. These findings demonstrate commonalities and differences in predictors of survival that may have implications for management of BL patients.

miRNAs associated with prostate cancer risk and progression.

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate cancer. The discussion highlights key findings from previous studies, which reported the role of miRNAs in risk and progression of prostate cancer, providing an understanding of the influence of miRNA on prostate cancer. Our review indicates that somewhat consistent results exist between these studies and reports on several prostate cancer related miRNAs. Present promising candidates are miR-1, -21, 106b, 141, -145, -205, -221, and -375, which are the most frequently studied and seem to be the most promising for diagnosis and prognosis for prostate cancer. Nevertheless, the findings from previous studies suggest miRNAs may play an important role in the risk and progression of prostate cancer as promising biomarkers.

Early onset pancreatic malignancies: Clinical characteristics and survival associations.

Diagnosed before age 50, early onset pancreatic malignancy (EOPM), is hypothesized to be a distinct subset of disease, although research is limited. To better characterize EOPM, and the effect of age at diagnosis on pancreatic cancer survival, we examined clinical characteristics and survival in EOPM and typical age-at-onset pancreatic malignancy (TOPM) cases. Vanderbilt University Medical Center (VUMC) Cancer Registry confirmed pancreatic adenocarcinomas (PDACs) and malignant pancreatic neuroendocrine tumors (PNETs) were evaluated. Clinical characteristics were compared using χ(2) tests. Overall survival was visualized with Kaplan-Meier functions; Cox proportional hazards regression was used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 1,697 pancreatic malignancies were diagnosed at the VUMC between 1988 and 2013. Of 1,407 PDACs, 118 (8.4%) were EOPM, which was associated with significantly better survival (adjusted HR: 0.82, 95% CI: 0.67-1.00). EOPM and TOPM PDACs significantly differed with regard to having multiple malignancies; survival associations significantly differed by race, stage of disease, treatment and multiple malignancies. Of 190 PNETs, 63 (33.1%) were EOPM, which was not significantly associated with survival (adjusted HR: 0.80, 95% CI: 0.46-1.40). Malignant neuroendocrine EOPM and TOPM cases significantly differed by stage of disease and tumor location; survival associations significantly differed by family history of pancreatic cancer, stage of disease and multiple malignancies. Differences in clinical characteristics and associations with survival were identified, indicating that EOPM is distinct from TOPM, and exists among both pancreatic adenocarcinomas and malignant pancreatic neuroendocrine tumors.

Association between genetic risk score for telomere length and risk of breast cancer.

PURPOSE: While leukocyte telomere length (TL) has been associated with breast cancer risk, limited information is available regarding the role of genetically-determined TL on breast cancer risk. We investigated whether aggregated TL-associated variants are associated with the risk of breast cancer in 2,865 breast cancer cases and 2,285 controls from the Shanghai Breast Cancer Genetics Study. METHODS: Six genetic variants, identified through a genome-wide association study (GWAS) of TL in European-ancestry participants, were included in the study. A separate sample [n = 1,536, from the Shanghai Women's Health Study (SWHS), for whom information on both phenotypical leukocyte TL and genetic information was collected] was used to evaluate the association of six variants with TL in Asians. Three genetic risk scores (GRSs), based on the number of alleles associated with shorter TL that each individual carries for the six variants, were derived for the study: un-weighted, internally weighted (from the SWHS), and externally weighted (from the European-ancestry GWAS study), and evaluated for their association with breast cancer risk by applying logistic regression analysis. RESULTS: Both internally and externally weighted GRSs were significantly associated with a decreased risk of breast cancer (OR 0.83, 95 % CI 0.72-0.95 and OR 0.84, 95 % CI 0.74-0.96, respectively, for tertile 3 vs. tertile 1). Non-genetic risk factors for breast cancer (i.e., age, years of menstruation/reproduction, oral contraceptive usage, and BMI) did not modify the association between GRSs and the risk of breast cancer. CONCLUSION: Our results suggest that short TL, determined by genetic factors, may be associated with a reduced susceptibility to breast cancer.