CA : A Cancer Journal for Clinicians

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Food, Nutrition, Physical Activity, and the Prevention of Cancer : a Global Perspective : 食物、栄養、身体活動とがんの予防 : 世界的展望(後篇)

Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer

The International Agency for Research on Cancer convened a workshop on the relationship between body fatness and cancer, from which an IARC handbook on the topic will appear. An executive summary of the evidence is presented.

/pdf/body-fatness-and-cancer-viewpoint-of-the-iarc-working-group-3tw0w2dik3.pdf

Body Fatness and Cancer — Viewpoint of the IARC Working Group

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

/pdf/asia-pacific-clinical-practice-guidelines-on-the-management-3qdf1cp1jm.pdf

Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and meta-analysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs = 2.01, 95% CI: 1.61–2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q = 136.68, p < 0.001, I2 = 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR = 1.56; 95% CI: 1.30–1.87), with no significant evidence of heterogeneity among studies (Q = 1.16, p = 0.56, I2 =0%). There were no significant publication bias (p = 0.79 for Egger's regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.26165

Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies.

Aims: To provide a quantitative assessment of the association between body mass index (BMI) and the risk of gastric cancer (GC), we summarized the evidence from prospective studies. Methods: Eligible studies published up to November 30, 2012 were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 24 prospective studies of BMI and GC risk with 41,791 cases were included in our analysis. Overall, both overweight (BMI of 25 to 30 kg/m2) and obesity (BMI of 30 kg/m2 or greater) were not associated with risk of total GC (overweight: SRR=1.01; 95% CI, 0.96-1.07; obesity: SRR=1.06, 95% CI 0.99-1.12). Furthermore, we found increased BMI was positively associated with the risk of gastric cardia cancer (GCC, SRR= 1.21 for overweight and 1.82 for obesity), but not with gastric non-cardia cancer (GNCC, SRR=0.93 for overweight and SRR=1.00 for obesity). Similar results were observed in a linear dose-response analysis. Conclusion: Based on meta-analysis of prospective studies, we find high BMI is positively associated with the risk of GCC, but not with GNCC. Impact: 1. Based on more definite and quantitative evidence than previously available, we found that increasing BMI was not a clear risk factor for total gastric cancer. 2. Increased BMI was positively associated with risk of gastric cardia cancer, but not with gastric non-cardia cancer.

https://cebp.aacrjournals.org/content/cebp/22/8/1395.full.pdf

Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies

Consumption of fruit, but not vegetables, may reduce risk of gastric cancer: Results from a meta-analysis of cohort studies

MicroRNAs are potentially very useful biomarkers in the diagnosis of cancer. We sought to identify specific microRNAs in peripheral blood mononuclear cells (PBMCs) whose levels might facilitate diagnosis of pancreatic cancer. We investigated PBMC microRNA expression in three independent cohorts [healthy, benign pancreatic/peripancreatic diseases (BPD), and pancreatic cancer], comprising a total of 352 participants. First, we used sequencing technology to identify differentially expressed microRNAs in PBMC of pancreatic cancer, BPD, and healthy controls (n = 20 in each group). Then the selected microRNAs were analyzed using the quantitative reverse transcriptase PCR assays in the remaining 292 samples. The predictive value of the microRNAs was evaluated by logistic regression models and the receiver operating characteristic curve (AUC). We found that miR-27a-3p level in PBMCs could discriminate pancreatic cancer from BPD with a sensitivity of 82.2% and specificity of 76.7% (AUC = 0.840; 95% CI, 0.787-0.885%). Combination of PBMC miR-27a-3p and serum CA19-9 levels provided a higher diagnostic accuracy with a sensitivity of 85.3% and specificity of 81.6% (AUC = 0.886; 95% CI, 0.837-0.923%). The satisfactory diagnostic performance of the panel persisted regardless of disease status (AUCs for tumor-node-metastasis stages I-III were 0.881, 0.884, and 0.893, respectively). PBMC miR-27a-3p level represents a potential marker for pancreatic cancer screening. A panel combining serum CA19-9 and PBMC miR-27a-3p level could have considerable clinical value in diagnosing pancreatic cancer.

https://cancerpreventionresearch.aacrjournals.org/content/canprevres/6/4/331.full.pdf

Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer

Although the American College of Gastroenterology colorectal cancer screening guidelines highlight cigarette smoking as a risk factor, cigarette smoking is still an arguably underappreciated risk factor for this disease, especially for its subsites: colon cancer (CC) and rectal cancer (RC). A literature search of MEDLINE and EMBASE was performed up to 30 April 2013 for prospective cohort studies. A random-effects meta-analysis was carried out to estimate the summary relative risks (SRRs) and 95% confidence intervals (CIs) for the associations. A total of 24 prospective studies, which reported data for cigarette smoking and incidence of CC and RC separately, were included. Our analysis showed that, compared with never-smokers, current smokers had a higher risk of RC than CC (CC: SRR=1.09, 95% CI, 1.01-1.18; RC: SRR=1.24, 95% CI, 1.16-1.39; PRC vs. CC=0.034), whereas former smokers had a similar risk of CC and RC. Current smokers had a significantly higher risk of proximal CC than distal CC (P=0.035). This meta-analysis suggests that cigarette smoking is associated with an increased risk of both CC and RC, and that the magnitude of the association is stronger for RC than that for CC.

Guoping Li

Papers

Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies.

Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies

Consumption of fruit, but not vegetables, may reduce risk of gastric cancer: Results from a meta-analysis of cohort studies

Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer

Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers.