Metachronous Gastric Cancer Research Articles

Molecular subtype switching in early-stage gastric cancers with multiple occurrences.

Multiple gastric cancers at the same time (synchronous) or recurrence after 1year (metachronous) are frequently encountered. Since their genetic profiles were not well elucidated, we molecularly subtyped the genetic events of synchronous and metachronous early-stage gastric cancers. We studied mismatch repair (MMR) genes in 84 tumors from 31 patients (15 synchronous and 16 metachronous) by immunohistochemistry. We performed microsatellite instability analysis and targeted sequencing of 58 significantly mutated genes (SMGs) in 35 tumors from thirteen patients. Genomic data from TCGA were used for comparisons with advanced-stage cancers. Among the 31 patients, at least one deficient-MMR (dMMR) tumor was observed in eight (26%). Of eight patients, seven showed a mixture of proficient-MMR (pMMR) and dMMR tumors. The one case with only dMMR had six recurrent tumors within 2years. To further subtype, we sequenced 58 SMGs in 35 samples (25 pMMR and 10 dMMR) from thirteen patients. In 35 samples, 163 mutations were identified, but none matched in almost cases, strongly indicating different clonal origins, whether synchronous or metachronous occurrences. Of the 25 pMMR cases, 1 belonged to Epstein-Barr virus (EBV), 24 belonged to chromosomal instability (CIN) subtypes. Of the thirteen cases, repetitive CIN, a mixture of CIN and MSI, a mixture of CIN and EBV, and repetitive MSI were observed in nine (70%), two (15%), one (8%) and one (8%), respectively. Despite multiple tumors occurring in the same patient simultaneously or several years apart, clonal origin was totally different. 'Switching' or 'mixing' of dMMR and pMMR, EBV or CIN occurred, which had clinical relevance with regard to immunotherapy.

Clinicopathologic characteristics and survival rate in patients with synchronous or metachronous double primary colorectal and gastric cancer

Clinicopathologic characteristics and survival rate in patients with synchronous or metachronous double primary colorectal and gastric cancer

Two steps forward and one step back.

Perioperative chemotherapy is the standard of care for localized gastric cancer (GC). In 2018, additional postoperative radiotherapy was found to be ineffective; although, docetaxel was found to be superior to epirubicin in perioperative three-drug chemotherapy regimens. Validated biomarkers are needed for benefit from immunotherapy in advanced-stage GC. Metachronous GC can be prevented by Helicobacter pylori eradication.

Gastric Xanthelasma: Innocent Bystander?

Introduction: Gastric xanthoma or xanthelasma are usually benign sharply demarcated yellow deposit of cholesterol underneath the skin, a rare finding during endoscopy. Their clinical significance is unknown; however they have been associated with gastric malignancy. Case Report: _A 62 year old male with a past medical history of colon cancer in 2005 treated with right hemicolectomy and chemotherapy in remission, seroconverted hepatitis C, atrial fibrillation, osteoarthritis, chronic kidney disease stage II was evaluated in the office for a screening colonoscopy. He mentioned his mother was diagnosed with gastric cancer at the age of 60, thus upper endoscopy was recommended. His physical exam was normal. His blood work showed a normal comprehensive metabolic panel with hemoglobin 15.5 and albumin of 4.4.Upper endoscopy showed two small nodular yellow areas, measuring 7-8 mm in size, on the proximal greater curvature of the body of the stomach. On microscopic examination, the lamina propria showed inclusion of foamy histiocytes with hematoxylin and eosin (H&E) staining. Immunohistochemical stain was positive for CD163, and negative for pancytokeratin and PAS stain negative for Whipple's disease. The absence of nuclear atypia and cytokeratins excluded the diagnosis of malignancy. These findings were suggestive of a gastric xanthoma. The surrounding gastric mucosa showed evidence of focal chronic inactive gastritis. Immunohistochemical stain for H. pylori was negative. The duodenum appeared normal. Discussion: Gastric xanthelasma or xanthomas (GX) are incidental relatively rare lesions found on upper endoscopy with the prevalence ranging from 0.23% to 7%. Clinically, the patient is asymptomatic, and most of the time endoscopy is performed for other reasons. Historically, GX has received little attention, maybe because clinically it has been always considered as a benign endoscopic finding. However more recent studies showed that there is a strong association between gastric xanthoma lesions and atrophic gastritis. It appears to be a close relationship between H. pylori infection, and GX. Treating H. pylori did not decrease the risk of gastric adenocarcinoma when GX was present. Some retrospective observational studies have gone as far as associating GX as a predictive marker for metachronous and synchronous gastric cancers, or even the development of gastric cancer. Previous partial gastric resection is associated with an increased incidence of GX.1857_A Figure 1 No Caption available.1857_B Figure 2 No Caption available.

PS02.222: CLINICAL CHARACTERISTICS AND MANAGEMENT OF GASTRIC TUBE CANCER AFTER ESOPHAGECTOMY

Abstract Background Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Methods Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Results Most cases were males. The median interval from TEC surgery to GTC occurrence was 68.1 months (6–190 months). Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. Conclusion GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important. Disclosure All authors have declared no conflicts of interest.

Gastric cancer: epidemiology, prevention, and therapy.

Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent trend of a decreasing incidence, in 2015 approximately 4.4billion individuals-more than half the world's population-were infected with H.pylori. The birth cohort pattern of decreased H.pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H.pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H.pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory-wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC.

116 SUCCESSFUL ERADICATION OF HELICOBACTER PYLORI REDUCES THE DEVELOPMENT OF METACHRONOUS GASTRIC CANCER AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER: A PROPENSITY MATCHING ANALYSIS

Helicobacter pylori infection is the most important risk factor for gastric cancer. Some randomized studies showed that successful H. pylori eradication after endoscopic resection of early gastric cancer (EGC) significantly reduced metachronous gastric cancer (MGC), whereas others showed that H. pylori eradication did not significantly contribute to reducing MGC. Our aim was to investigate the effect of H. pylori eradication on the development of MGC after endoscopic submucosal dissection (ESD) for EGC. Between October 2007 and October 2015, at our hospital, 701 consecutive patients with EGC underwent curative resection using the expanded indications for ESD according to the criteria in the Japanese Gastric Cancer Treatment Guidelines 2014. Of these patients, 378 who contracted H. pylori infection at the time of ESD were enrolled. Patients with familial adenomatous polyposis, those who had undergone surgical gastrectomy, or those whose follow-up duration was less than 1 year, were excluded. The patients included were divided into two groups as follows: those who failed or did not undergo H. pylori eradication (persistent group, n = 220), and those who successfully underwent H. pylori eradication (eradicated group, n = 128). We retrospectively compared the incidence of the development of MGC between the groups by using propensity score (PS) matching to reduce the effects of selection bias and potential confounding factors. The patients in the persistent group had significantly older age, lighter weight, and larger tumor size than the patients in the eradicated group (p < 0.01, p = 0.05, p = 0.01). After PS matching, 128 pairs of patients between the persistent and eradicated groups showed no significant difference in any covariate. The MGC developed in 22 patients (10.0%) in the persistent group and 5 patients (3.9%) in the eradicated group during the median follow-up period of 38.8 months (range, 12.4–114.0 months) and 40.5 months (range, 25.9–105.7 months), respectively. Before matching, the 5-year cumulative incidence rate of MGC was not significantly different between the persistent and eradicated groups (11.3% vs 3.8%, p = 0.06). After matching, the rate was significantly higher in the persistent group than the eradicated group (14.2% vs 3.8%, p = 0.01). In the Cox proportional hazard analysis, the eradicated group was not significantly associated with preventing MGC before matching (HR = 0.40, p = 0.07). However, the eradicated group was significantly associated with preventing MGC after matching (HR = 0.30, p = 0.02). Although this is a retrospective cohort study conducted at a single institution by using PS matching to adjust the background factors in the real world, it demonstrated that successful H. pylori eradication may reduce the development of MGC after ESD of EGC.

Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial

Whether eradication of Helicobacter pylori reduces the incidence of metachronous gastric cancer (MGC) is still debatable. We aimed to evaluate the long-term effect of H pylori eradication on the development of MGC after endoscopic gastric tumor resection. We undertook an open-label, prospective, randomized controlled trial at a tertiary hospital in Seoul, Korea. Participants were recruited during April 2005 to February 2011 and followed until December 2016. We assigned 898 patients with H pylori infection treated with endoscopic resection (ER) for gastric dysplasia or early gastric cancer to receive (n=442) or not receive (n=456) eradication therapy using a random-number chart. Eradication group patients received oral omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for a week, whereas control group patients received no H pylori treatment. The primary outcome was the incidence of MGC (intention-to-treat analysis). The 877 patients who attended≥1 follow-up examination (eradication group, 437; control group, 440) were analyzed. Median follow-up was 71.6 months (interquartile range, 42.1-90.0). MGC developed in 18 (4.1%) eradication and 36 (8.2%) control group patients (log-rank test, P= .01). In our yearly analysis, the effect of eradication showed a significant difference in 5 years after allocation (log-rank test, P= .02). The adjusted hazard ratio for the control group was 2.02 (95% CI, 1.14-3.56; P= .02), compared with the eradication group. H pylori eradication significantly reduces the incidence of MGC after ER of gastric tumors and should be considered for H pylori-positive gastric tumor patients treated with ER. (Clinical trial registration number: NCT01510730.).

A retrospective study of endoscopic treatment on early gastric cancer in a single center for 10 years

Objective To evaluate the efficacy, safety and risk factors of endoscopic treatment for patients with early gastric cancer. Methods A retrospective study was conducted in a single center and data was collected from 186 early gastric cancers in 168 pathologically confirmed patients who received endoscopic treatment in Peking Union Medical College Hospital from January 2006 to December 2015. The cases were divided into different groups according to indications of endoscopic treatment. The curative resection rate and complication rate were analyzed. Post-resection outcomes were evaluated by long-term surveillance. Results The curative resection rate was 86.9%(73/84)in the group with absolute indications, 61.7%(50/81)in the group with expanded indications, and 33.3%(7/21) in the group beyond indications (P<0.01). Multivariate analysis revealed that the significant independent predictors for curative resection included lower third location of stomach, no ulceration, ≤2 cm at diameter, no adhesion, and well-differentiation in histopathology. In the expanded indications group, discordance of differentiation type and deeper invasion mainly resulted in non-curative resection in en bloc lesions. The rate of bleeding and perforation was 4.8% (9/186) and 3.8% (7/186), respectively. The perforation rate was significantly lower in the lesions located in the lower third of stomach, without adhesion or performed by en bloc resection. During a median follow-up period of 22.3 months, 154 patients were followed successfully. The incidence of synchronous and metachronous gastric cancers in curative resected lesions was 7.5% (8/106) and 0.9% (1/106), respectively. Conclusion Endoscopic resection is an optimal treatment with high curative resection rate for early gastric cancer patients with absolute indications. Patients with expanded indications should take precise preoperative evaluation to avoid higher risk of non-curative resection endoscopically. Close follow-up is necessary for synchronous and metachronous gastric cancers after endoscopic resection. Key words: Stomach neoplasms; Endoscopic mucosal resection; Endoscopic submucosal dissection; Indication; Curative resection

Clinical characteristics and management of gastric tube cancer after esophagectomy.

Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Most cases were males. The median interval from TEC surgery to GTC occurrence was 57 (6.5-107.5) months. Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important.

Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer

BackgroundPatients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent (metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear.MethodsIn this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up.ResultsA total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001).ConclusionsPatients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT02407119.)

Incidence and treatment of metachronous gastric cancer after proximal gastrectomy.

Proximal gastrectomy (PG) is a widely accepted function-preserving surgical procedure; however, the incidence and treatment of metachronous gastric cancer (MGC) after PG have been the subject of a number of reports. We collected data from 1576 consecutive patients who underwent gastrectomy for gastric cancer between January, 2003 and December, 2010, and analyzed the outcomes of 671 patients treated with PG or distal gastrectomy (DG) for cT1N0 disease. We also discuss the treatments for MGC. MGC was diagnosed within a median follow-up of 52.8months after PG and DG in six (6.6%) and nine (1.8%) patients, respectively. The cumulative prevalence of MGC after PG was significantly higher than that after DG; P = 0.005. Univariate and multivariate analysis revealed male sex and PG as significant risk factors for MGC (P = 0.014 and P = 0.026, respectively). Five of the six patients who underwent PG were treated by endoscopic submucosal dissection. The incidence of MGC after PG was significantly higher than that after DG. However, most of the MGCs that developed after PG could be treated by endoscopic submucosal dissection.

Helicobacter pylori Eradication Prevents the Occurrence of Metachronous Gastric Cancer

<i>Helicobacter pylori</i> Eradication Prevents the Occurrence of Metachronous Gastric Cancer

Helicobacter pylori Eradication Therapy and Gastric Cancer Prevention

Gastric cancer is the most common cancer in Korea and the fifth most common cancer globally. Helicobacter pylori (H. pylori) infection is considered the main etiologic agent for gastric cancer development. Most regional guidelines for H. pylori treatment recommend treating the organism to prevent gastric cancer in the high-risk group. However, evidence that such a strategy can also be applied to the general population, especially in terms of the preventive effect and safety, has not been adequately presented yet. Although a meta-analysis in the general population suggested effectiveness in decreasing gastric cancer incidence, individual studies should be critically reviewed to evaluate the soundness of the evidence. Recently published, long-term, Korean studies on metachronous gastric cancer prevention ended the controversies from previous short-term studies and confirmed the effectiveness. Currently, further prospective, large, randomized studies are ongoing in the general population and will provide more definitive, high-level evidence on this gastric cancer prevention strategy in the next decade.

Eradication Does Not Prevent Metachronous Gastric Cancer

Helicobacter pylori infection is a known risk factor for gastric cancer (GC). Eradication of the infection may reverse some GC precursor states, such

Long-Term Effects of Helicobacter pylori Eradication on Metachronous Gastric Cancer Development.

Background/AimsGastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC).MethodsPatients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status.ResultsIn total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylori-eradicated group than in the persistent group during follow-up (p=0.029). In patients <70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development.ConclusionsH. pylori eradication might prevent the development of metachronous cancer in patients <70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC.

Metachronous Gastric Cancer Following Curative Endoscopic Resection of Early Gastric Cancer.

This review article summarizes knowledge about metachronous gastric cancer (MGC) occurring after curative endoscopic resection (ER) of early gastric cancer (EGC), treatment outcomes of patients who developed MGC, and efficacy of Helicobacter pylori eradication to prevent MGC. The incidence of MGC following curative ER increases over time and is higher than in patients undergoing gastrectomy. Increasing age and multifocal EGC are independent risk factors for developing MGC. An MGC following curative ER is usually a small (<20 mm) and differentiated intramucosal cancer. Most MGC lesions are found at an early stage on semiannual or annual surveillance endoscopy and are successfully treated by further ER, with excellent long-term outcomes. Eradication of H. pylori may reduce the risk of MGC following ER of EGC, but further prospective studies with long-term outcomes are required. Surveillance endoscopy following gastric ER should be continued indefinitely, due to the risk of MGC even after successful H. pylori eradication. Risk stratification and tailored endoscopic surveillance schedules need to be developed.

Novel risk stratification for metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer

This study stratified the risk of developing metachronous gastric cancer (MGC) after curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) to enable customization of endoscopic surveillance for MGC. A total of 1115 patients who underwent curative ESD based on the expanded criteria for differentiated EGC from 2005 to 2014 at a single tertiary hospital were enrolled in this retrospective cohort study. They were followed up with annual endoscopy for a median of 50.1 months. Helicobacter pylori and histologic intestinal metaplasia (IM) were evaluated. The Kaplan-Meier method and Cox regression analysis were used for risk stratification. Three risk groups were identified: group 1 comprised patients with a synchronous neoplasm; group 2 comprised male patients with corpus IM; and group 3 comprised male patients without corpus IM or female patients. The 5- and 7-year cumulative risks (95% confidence interval [CI]) for metachronous recurrence were 15.1% (95% CI, 7.7-22.5) and 26.1% (95% CI, 14.9-37.3), respectively, in group 1; 5.6% (95% CI, 3.1-8.1) and 9.3% (95% CI, 5.4-13.2), respectively, in group 2; and 3.8% (95% CI, 1.6-6.0) and 4.9% (95% CI, 2.4-7.4), respectively, in group 3 (P< .001 by log-rank test). The incidence of MGCs increased constantly even after 5 years in groups 1 and 2 but not in group 3. There was not enough evidence to show an association between H pylori eradication and metachronous recurrence in the data. Meticulous annual endoscopic surveillance for MGC for more than 5 years is recommended for patients with synchronous neoplasm. Endoscopic surveillance may also be extended beyond 5 years in male patients with corpus IM.

Long-Term Outcomes of Using Endoscopic Submucosal Dissection to Treat Early Gastric Cancer.

Endoscopic submucosal dissection (ESD) is becoming the main procedure for the resection of early gastric cancer (EGC). The absolute indications for treating EGC with endoscopic resection were established by the Japanese Gastric Cancer Association and have been generally accepted. However, the absolute indications for treating EGC are rather strict, and expanded indications have been developed. Many studies have reported favorable long-term outcomes for patients who received curative resection for the expanded indication. ESD preserves the stomach, thereby improving patients’ quality of life compared to surgery; however, a generally higher incidence of metachronous gastric cancer has been reported after ESD for EGC. Therefore, clinicians must pay careful attention during surveillance endoscopy, even after a curative ESD.

Abstract LB-092: High impact of methylation accumulation on cancer risk: 5-year follow-up of a multicenter prospective cohort study

Abstract Aberrant DNA methylation can be accumulated in normal-appearing tissues, and its degree can be correlated with cancer risk [Hattori, Genome Med, 8:10, 2016]. Such accumulation is especially prominent in inflammation-associated cancers, including gastric cancer. To bring the findings into cancer risk diagnosis, we conducted a multicenter prospective cohort study with 826 patients [Asada, Gut, 64:388, 2015]. Between 2008 and 2010, 826 patients after endoscopic treatment of gastric cancer and without current H. pylori infection were enrolled, and a gastric biopsy was collected. Methylation levels of pre-defined three marker genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were classified into quartiles according to methylation levels of individual genes (Q1, the lowest; Q4, the highest). Among the 826 enrolled patients, 795 patients received annual follow-ups by endoscopy with a median period of 5.46 years (interquartile range: 3.95 - 6.09). By the end, 133 patients developed a metachronous gastric cancer, and 116 of them developed a cancer after 1 year of the enrollment (authentic metachronous cancer). Kaplan-Meier analysis showed that Q4 had a higher cumulative incidence of metachronous gastric cancer than Q1 with p-values of &amp;lt;0.001 to 0.004 (log-rank test). Multivariate analyses adjusted for hospital, gender and age, pepsinogen index, history of endoscopic treatment, smoking and green vegetable intake also showed that Q4 had significantly high HRs compared with Q1, being 3.0 (95%CI: 1.58 to 5.72, p=0.0017) for miR-124a-3 [Maeda, Gut, online]. The results clearly showed that accumulation levels of aberrant DNA methylation can be used for cancer risk diagnosis. Even among the patients who carried a high risk of metachronous gastric cancer, cancer risk stratification was achieved. The strong influence of methylation accumulation on gastric cancer risk indicated a large contribution of aberrant DNA methylation to H. pylori infection-induced gastric carcinogenesis. Epigenetic cancer risk diagnosis is now becoming real. Citation Format: Masahiro Maeda, Takeshi Nakajima, Ichiro Oda, Taichi Shimazu, Nobutake Yamamichi, Takao Maekita, Kiyoshi Asada, Chizu Yokoi, Takayuki Ando, Takeichi Yoshida, Sohachi Nanjo, Mitsuhiro Fujishiro, Takuji Gotoda, Masao Ichinose, Toshikazu Ushijima. High impact of methylation accumulation on cancer risk: 5-year follow-up of a multicenter prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2017-LB-092