Yoshiki Tabuchi

Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population

BackgroundGenetic polymorphisms of DNA repair enzymes may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interactions between polymorphisms of repair genes and tobacco smoking in colorectal cancer.MethodsThe case-control study involved sixty-eight colorectal cancer patients and 121 non-cancer controls divided into non-smokers and smokers according to pack-years of smoking. The genetic polymorphisms of DNA repair enzymes,OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu and XRCC1 Arg399Gln, were examined using PCR-RFLP.ResultsThe MUTYH Gln324His showed strong significant associations with a risk of colorectal cancer (crude odds ratio [OR] 3.30, 95% confidence interval [95%CI] 1.44–7.60, p = 0.005; adjusted OR3.53, 95%CI 1.44–8.70, p = 0.006). The ORs for the APEX1 Asp148Glu were statistically significant (crude OR 2.69, 95%CI 1.45–4.99, p = 0.002; adjusted OR 2.33, 95%CI 1.21–4.48, p = 0.011). The ORs for the MUTYH Gln324His and the APEX1 Asp148Glu were statistically significant for colon cancer (adjusted OR 3.95, 95%CI 1.28–12.20, p = 0.017 for MUTYH Gln324His ; adjusted OR 3.04, 95%CI 1.38–6.71, p = 0.006 for APEX1 Asp148Glu). The joint effect of tobacco exposure and the MUTYH Gln324His showed a significant association with colorectal cancer risk in non-smokers (adjusted OR 4.08, 95%CI 1.22–13.58, p = 0.022) and the APEX1 Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95%CI 1.80–13.99, p = 0.002). However, the distributions of OGG1 Ser326Cys and XRCC1 Arg399Gln were not associated with a colorectal cancer risk.ConclusionOur findings suggest that the MUTYH Gln324His and the APEX1 Asp148Glu constitutes an increased risk of colorectal cancer, especially colon cancer. The MUTYH Gln324His is strongly associated with colorectal cancer susceptibility in never smoking history, whereas the APEX1 Asp148Glu genotype constitutes an increased risk of colorectal cancer when accompanied by smoking exposure.

MUTYH Gln324His gene polymorphism and genetic susceptibility for lung cancer in a Japanese population.

BackgroundGenetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer.MethodsWe analyzed associations among OGG1 Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese.ResultsThe results showed that the MUTYH His/His genotype compared with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31–7.00, p = 0.010), whereas there was no significant increase for the Gln/His genotype (adjusted OR 1.35, 95%CI 0.70–2.61, p = 0.376). The MUTYH His/His genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95–6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89–11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1 Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH His/His genotype compared with the Gln/Gln genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22–12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60–11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also no significant risk for lung cancer.ConclusionOur findings suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.

Serum carcinoembryonic antigen levels and proliferating cell nuclear antigen labeling index for patients with colorectal carcinoma. Correlation with tumor progression and survival.

Clinicopathologic variables, carcinoembryonic antigen (CEA), nuclear DNA ploidy, and proliferating cell nuclear antigen labeling index (PCNA LI) have been studied for their effect on patients with various types of cancer.

Immunohistochemical evaluation of thymidylate synthase in gastric carcinoma using a new polyclonal antibody

Before this study was conducted, the clinical and therapeutic significance of immunohistochemical evaluation of thymidylate synthase (TS) in patients with gastric carcinoma had not yet been clarified.

Evaluation of argyrophilic nucleolar organizer region and proliferating cell nuclear antigen in colorectal cancer

Background and Objectives: Information on cellular proliferation is gaining importance for predicting prognosis in several cancers. To clarify the clinicopathological significance of argyrophilic nucleolar organizer region (AgNOR), proliferating cell nuclear antigen (PCNA), and DNA ploidy pattern, we studied their correlations with clinicopathological factors in colorectal cancer.

Appendiceal intussusception induced by tubulovillous adenoma with carcinoma in situ: report of a case.

Appendiceal intussusception is an uncommon pathologic condition; however, villous adenoma of the appendix is a distinctly rare entity. We report herein a case of appendiceal intussusception induced by tubulovillous adenoma with carcinoma in situ. A 67-year-old man was admitted to our hospital with a 1-year history of lower abdominal pain for investigation. Barium enema showed a filling defect with an irregular surface in the cecum, and colonoscopy revealed a cecal tumor with a granular surface. Pathological examination of biopsy samples revealed tubulovillous adenoma with well-differentiated adenocarcinoma, and a diagnosis of cecal cancer in tubulovillous adenoma was made. Surgery was performed and the resected specimen was found to contain a tumor arising from the appendix. The tumor was 5.5 × 4.5 cm in size in the cecal cavity, and the appendix had invaginated into the cecum at its base. The cut surface of the appendix showed the villous tumor filling the appendiceal lumen and projecting into the cecal cavity. Microscopic examination revealed well-differentiated adenocarcinoma in tubulovillous adenoma. To the best of our knowledge, this is the first report of appendiceal intussusception caused by tubulovillous adenoma with carcinoma of the appendix.

Carcinoembryonic antigen levels of peripheral and draining venous blood in patients with colorectal cancer : correlation with survival

Correlations between preoperative carcinoembryonic antigen (CEA) levels of peripheral (p‐CEA) and draining blood (d‐CEA), the CEA gradient between d‐CEA and p‐CEA (d‐p CEA gradient) levels, and survival after resection of cancer lesions were examined in 94 patients with colorectal cancer. Survival rates of patients with normal p‐CEA and d‐CEA levels and d‐p CEA gradient levels (<5 ng/ml) were significantly better than those of patients with abnormal levels (≥5 ng/ml), and the 5‐year survival rates were, respectively, 62%, 69%, and 72% in the former and 42%, 41%, and 35% in the latter. The differences in the 5‐year survival rates between patients with normal and abnormal d‐p CEA gradient, d‐CEA, and p‐CEA levels were 37%, Z8%, and 20%, respectively. Furthermore, the positive rates of d‐CEA levels (64%) and d‐p CEA gradient levels (48%) were higher than that of p‐CEA levels (36%). However, some significant differences in background variables also were found between the respective groups of patients with normal and abnormal p‐CEA and d‐CEA levels and d‐p CEA gradient levels. These results suggest that patients with poor prognoses are examined more effectively by determining their d‐p CEA gradient and d‐CEA levels than their p‐CEA levels, and that CEA may be expressed as a quantitative sum total of various pathophysiologic variables of patients with colorectal cancer but not as an independent prognostic variable. Cancer 1992; 69:2411‐2417.

Expression of nm23-H1 in colorectal cancer: no association with metastases, histological stage, or survival.

The correlations of nm23-H1 expression in primary cancer lesions with the already confirmed 14 prognostic variables and survival were examined in 52 advanced colorectal cancer patients, because the clinical roles of nm23-H1 expression in the cancer lesions remain controversial. An immunohistochemical expression of nm23-H1 was found in 23 lesions (positive group) but not found in 29 lesions (negative group). No significant difference between the positive and negative groups was found according to 12 clinicopathological variables including vascular invasion, lymph node and liver metastases, and histological stage. The carcinoembryonic antigen levels (21.5±33.4 ng/ml) of the draining venous blood and argyrophilic nucleolar organizer regions score (3.35±1.36 per nucleus) of the cancer cells in the positive group were not significantly different from those (34.1±102.9 ng/ml and 3.32±1.00 per nucleus, respectively) in the negative group. In addition, no significant difference was found in the survival curves or the 5-year survival rates of the positive and negative groups. From these results, it may be concluded that the nm23-H1 expression was not associated with the aforementioned prognostic variables and the prognosis of advanced colorectal cancer patients.

Liver metastases induced by implantation of VX2 cancer into the gastrointestine

An experimental model with a high frequency of spontaneous liver metastases was induced by implantation of VX2 cancer cells into the gastrointestinal walls of 36 rabbits, and the developmental process of primary cancer lesions and metastases was examined histologically. Gastric and colonic cancer lesions showed similar growth patterns in both primary and metastatic lesions: the average diameter of primary lesions enlarged from 0.7-0.8 cm on Day 7 to 2.4-2.8 cm on Day 28. The frequency and average diameter of liver metastases were 25% and microscopically certificated levels on Day 14, 25% and 3 mm on Day 21, and 50% and 8 mm on Day 28 in the gastric wall-implantation group. They were, respectively, 20% and microscopically recognized levels on Day 14, 40% and 2 mm on Day 21, and 80% and 9 mm on Day 28 in the colonic wall-implantation group. Thus, the frequency and diameter of the metastases increased in parallel with the primary cancer growth. Liver metastases occurred only in animals with vascular invasion in primary lesions, though none of the animals with the invasion always showed the metastases. These results suggest that vascular invasion of cancer cells in the primary lesions may be a premise of liver metastases, and that this experimental model may be utilized as a useful tool for studying many aspects of the pathogenesis and/or therapy of the spontaneous liver metastases in gastrointestinal cancer.

Clinicopathologic variables affecting survival of distal colorectal cancer patients with macroscopic invasion into the adjacent organs.

A total of 506 distal colorectal cancer patients were classified into two groups, to clarify the variables affecting survival of the patients with macroscopic invasion into the adjacent organs: 47 cases showed invasion (invasive group) while the other did not show invasion (noninvasive group). Differences between the invasive and noninvasive groups were found in eight variables; female, large tumor size, gross types 3 and 4, moderately or poorly differentiated adenocarcinomas and signet-ring cell or mucinous carcinomas, deep cancer invasion, lymphatic invasion, peritoneal and liver metastases, and curability B-C were found significantly more frequently in the invasive group. The survival curve of the former was significantly (P<0.05) lower than that of the latter. However, no significant difference was found between the survival curves of the patients with curability A (no residual tumors) in both groups. A multivariate analysis in the invasive groups revealed six variables to be significantly related to a good prognosis including a young age, females, a location above the peritoneal reflection, well differentiated adenocarcinoma, negative lymphatic invasion and curability A. Surgery with curability A should be performed to improve the survival in distal colorectal cancer patients with macroscopic invasion into the adjacent organs.