AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations...AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.展开更多
BACKGROUND Recent advances in endoscopic technology,especially magnifying endoscopy with narrow band imaging(ME-NBI)enable us to detect superficial esophageal squamous cell carcinoma(ESCC),but determining the appropri...BACKGROUND Recent advances in endoscopic technology,especially magnifying endoscopy with narrow band imaging(ME-NBI)enable us to detect superficial esophageal squamous cell carcinoma(ESCC),but determining the appropriate method of resection,endoscopic resection(ER)vs surgical resection,is often challenging.Recently,several studies have reported that 18F-fluorodeoxyglucose positron emission tomography(FDG-PET)is a useful indicator for decision-making regarding treatment for superficial ESCC.Although,there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC.And,there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.This study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for ESCC.AIM To investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.METHODS A database of all patients with superficial ESCC who had undergone both MENBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed.FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background,or not.The invasion depth of ESCC was classified according to the Japan Esophageal Society.Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC.Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.RESULTS A total of 82 lesions in 82 patients were included.FDG-PET showed positive uptake in 29(35.4%)lesions.Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension(P=0.014),pathological depth of tumor invasion(P<0.001),infiltrative growth pattern(P<0.001),histological grade(P=0.002),vascular invasion(P=0.001),and lymphatic invasion(P<0.001).On multivariate analysis,only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility(P=0.018).The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae and T1b upper submucosal layer were 68.4%/79.4%/50.0%/89.3%/76.8%,respectively,and those of Type B3 for the depth of T1b middle and deeper submucosal layers(SM2 and SM3)were 46.7%/100%/100%/89.3%/90.2%,respectively.On the other hand,those of FDGPET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%,respectively,whereas,if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy,the sensitivity,specificity,PPV,NPV,and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%,respectively.CONCLUSION FDG uptake was correlated with the invasion depth of superficial ESCC.Combined use of FDG-PET and ME-NBI,especially with the microvascular findings of Type B2 and B3,is useful to determine whether ER is indicated for the lesion.展开更多
Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigate...Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.展开更多
AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-cont...AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A)genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Signif icant interactions between ADH2, ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a signif icantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ADH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with the ALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele. CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also signifi cant gene-gene and gene- environment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.展开更多
AIM: To quantitatively evaluate the impact of smoking on tooth loss.METHODS: We performed a Pub Med search to identify published articles that investigated the risk of tooth loss by smoking, from which RRs and their v...AIM: To quantitatively evaluate the impact of smoking on tooth loss.METHODS: We performed a Pub Med search to identify published articles that investigated the risk of tooth loss by smoking, from which RRs and their variance with characteristics of each study were extracted. The random-effects models were used to derive a pooled effect across studies. Potential sources of heterogeneity on the characteristics of the study and their influence on the pooled effect size were investigated using metaregression models. RESULTS: We identified 24 studies containing a total of 95973 participants for analysis. The pooled RR of ever-smokers compared with never- smokers was 1.73(95%CI: 1.60-1.86, P < 0.001). In meta-regression analysis, only the mean age of participants alone was identified as a statistically significant source of heterogeneity. The effect of smoking on tooth loss was stronger when the mean age of study participants was higher, indicating possible enhancement of tooth loss due to aging by smoking. RR was significantly lower in former smokers(1.49, 95%CI: 1.32-1.69, P < 0.001) than in current smokers(2.10, 95%CI: 1.87-2.35, P < 0.001), indicating the substantial benefit of smoking cessation for reducing the risk of tooth loss.CONCLUSION: Smoking is an independent risk factor for tooth loss regardless of many other confounders. Smoking cessation may attenuate this effect.展开更多
Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.
基金Supported by Japanese Ministry of Health,Labor and Welfare
文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.
文摘BACKGROUND Recent advances in endoscopic technology,especially magnifying endoscopy with narrow band imaging(ME-NBI)enable us to detect superficial esophageal squamous cell carcinoma(ESCC),but determining the appropriate method of resection,endoscopic resection(ER)vs surgical resection,is often challenging.Recently,several studies have reported that 18F-fluorodeoxyglucose positron emission tomography(FDG-PET)is a useful indicator for decision-making regarding treatment for superficial ESCC.Although,there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC.And,there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.This study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for ESCC.AIM To investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.METHODS A database of all patients with superficial ESCC who had undergone both MENBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed.FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background,or not.The invasion depth of ESCC was classified according to the Japan Esophageal Society.Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC.Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.RESULTS A total of 82 lesions in 82 patients were included.FDG-PET showed positive uptake in 29(35.4%)lesions.Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension(P=0.014),pathological depth of tumor invasion(P<0.001),infiltrative growth pattern(P<0.001),histological grade(P=0.002),vascular invasion(P=0.001),and lymphatic invasion(P<0.001).On multivariate analysis,only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility(P=0.018).The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae and T1b upper submucosal layer were 68.4%/79.4%/50.0%/89.3%/76.8%,respectively,and those of Type B3 for the depth of T1b middle and deeper submucosal layers(SM2 and SM3)were 46.7%/100%/100%/89.3%/90.2%,respectively.On the other hand,those of FDGPET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%,respectively,whereas,if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy,the sensitivity,specificity,PPV,NPV,and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%,respectively.CONCLUSION FDG uptake was correlated with the invasion depth of superficial ESCC.Combined use of FDG-PET and ME-NBI,especially with the microvascular findings of Type B2 and B3,is useful to determine whether ER is indicated for the lesion.
基金Supported by A Grant-in-Aid for Scientific Research from the Japanese Ministry of Education,Culture,Sports,Science and Technology
文摘Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.
基金(in part) A Grant-in Aid for International Scientifi c ResearchSpecial Cancer Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan, No. 11137311Major International (Regional) Joint Research Projects from the National Natural Science Foundation of China (NSFC), No. 30320140461
文摘AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A)genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Signif icant interactions between ADH2, ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a signif icantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ADH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with the ALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele. CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also signifi cant gene-gene and gene- environment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.
基金Supported by Grant-in-Aid for the Third Term Comprehensive 10-year Strategy for Cancer Control,No.H20-3rd-002Grant-in-Aid for Cancer Research,Grant No.13-21-13-1 from the Japanese Ministry of Health,Labor and Welfare
文摘AIM: To quantitatively evaluate the impact of smoking on tooth loss.METHODS: We performed a Pub Med search to identify published articles that investigated the risk of tooth loss by smoking, from which RRs and their variance with characteristics of each study were extracted. The random-effects models were used to derive a pooled effect across studies. Potential sources of heterogeneity on the characteristics of the study and their influence on the pooled effect size were investigated using metaregression models. RESULTS: We identified 24 studies containing a total of 95973 participants for analysis. The pooled RR of ever-smokers compared with never- smokers was 1.73(95%CI: 1.60-1.86, P < 0.001). In meta-regression analysis, only the mean age of participants alone was identified as a statistically significant source of heterogeneity. The effect of smoking on tooth loss was stronger when the mean age of study participants was higher, indicating possible enhancement of tooth loss due to aging by smoking. RR was significantly lower in former smokers(1.49, 95%CI: 1.32-1.69, P < 0.001) than in current smokers(2.10, 95%CI: 1.87-2.35, P < 0.001), indicating the substantial benefit of smoking cessation for reducing the risk of tooth loss.CONCLUSION: Smoking is an independent risk factor for tooth loss regardless of many other confounders. Smoking cessation may attenuate this effect.
基金This research was supported in part by the Japan Agency for Medical Research and Development(AMED)(JP15ck0106096 to TK)Japan Science and Tech-nology Agency(JST)Core Research for Evolutionary Science and Technology(JPMJCR1689 to RH)+5 种基金Artifi-cial Intelligence,Big Data,IoT,Cyber Security Integration Project of the Public/Private R&D Investment Strategic Expansion Program(JPMJCR18Y4 to RH)the Japan Soci-ety for the Promotion of Science(JSPS)Grant-in-Aid for Scientific Research(S)(17H06162 to HN),Grant-in-Aid for Scientific Research(B)(20H03695 to KS),Grants-in-Aid for the Tailor-Made Medical Treatment Program(BioBank Japan Project)from the Japanese Ministry of Education,Culture,Sports,ScienceandTechnology(MEXT),Princess Takamatsu Cancer Research Fund,and National Cancer Center Research and Development Fund(NCC Biobank and NCC Core Facility).The J-MICC study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer(No.17015018 to KW)Innovative Areas(No.221S0001 to KW)from MEXTby JSPS Grant-in-Aid for Scientific Research Grant(No.16H06277[CoBiA])The JPHC Study was supported by National Cancer Center Research and Development Fund since 2011(latest grant number:2020-J4)and a Grant-in-Aid for Cancer Research from the Ministry of Health,Labor and Welfare of Japan(1989-2010).ToMMoissupportedinpartbyMEXT-JSTand AMED(most recent grant numbers:JP20km0105001 and JP20km0105002)Iwate Tohoku Medical Megabank Orga-nization(Iwate Medical University)is supported in part by MEXT-JST and AMED(most recent grant numbers:JP20km0105003 and JP20km0105004).
文摘Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.
