Atsuko Shibata

Increasing colorectal cancer incidence rates in Japan

We examined trends of colorectal cancer incidence rates among Japanese (Miyagi Prefecture) and United States (US) whites (State of Connecticut) between 1959 and 1992. Age‐standardized rates in Japan have increased dramatically and are now similar to US white rates. For both colon and rectum, age‐specific rates in Japanese men born after 1930 exceed those in US whites, and the Japanese excess increases with year of birth. Similar patterns are evident for women. The current trends suggest that colorectal cancer will become a major source of morbidity and mortality in Japan, as these young Japanese age and their risks increase.

Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk.

It seems unlikely that the large ethnic differences in prostate cancer risk can be explained completely by ethnic differences in diet or other lifestyle characteristics. Instead, the differences may be due to ethnic variation in endogenous factors, such as androgen metabolism or inherited susceptibility.

Subjects with TNF-A-857TT and -1031TT genotypes showed the highest Helicobacter pylori seropositive rate compared with those with other genotypes

BackgroundA possible association between Helicobacter pylori seropositivity and tumor necrosis factor (TNF) A G-308A has been reported in Korea. The present study examined the associations of H. pylori with functional polymorphisms, TNF-A G-308A, C-857T, and T-1031C, and TNF-B A252G in Japanese subjects.MethodsThe total of 1374 study subjects included 241 outpatients who participated in an H. pylori eradication program (HPE), 679 first-visit outpatients (FVO) at a regional cancer hospital, and 454 local residents who received a health checkup examination (HCE).ResultsThe frequency of the TNF-A -308A allele was only 1.3% of 480 chromosomes in the HPE group, so the FVO and HCE groups were not genotyped for that polymorphism. The genotype frequency of TNF-A C-857T was 69.2% CC, 27.7% CT, and 3.1% TT; that of TNF-A T-1031C was 69.4% TT, 28.1% TC, and 2.5% CC; and that of TNF-B A252G was 36.8% AA, 48.2% AG, and 15.0% GG. TNF-A -857T was tightly linked to TNF-A -1031T and TNF-B 252A. No significant associations between H. pylori seropositivity and polymorphisms of TNF-A C-857T and TNF-B A252G were observed. However, a reduced odds ratio adjusted for sex, age, and recruitment source was observed for TNF-A -1031CC (0.43; 95% confidence interval, 0.20–0.91) relative to TNF-A -1031TT. Subjects with TNF-A -857CC and -1031CC showed the lowest seropositivity (38.2% of 34 participants), while those with TNF-A -857TT and -1031TT showed the highest (66.7% of 42 participants).ConclusionsThis study suggests that the possibly high expression genotype of TNF-A may increase susceptibility to persistent H. pylori infection.

GENETIC POLYMORPHISMS IN THE ANDROGEN RECEPTOR AND TYPE II 5α-REDUCTASE GENES IN PROSTATE ENLARGEMENT

PURPOSE We examined the association of androgen receptor gene cytosine-adenine-guanine (CAG) repeat length and the 2 single nucleotide polymorphisms A49T and V89L in the type II 5 alpha-reductase gene with prostate enlargement measured as the weight of the surgically removed prostate. MATERIALS AND METHODS A total of 68 men with a prostate weighing 80 gm. or greater were compared with 197 controls with a prostate weighing less than 80 gm. These men had undergone radical prostatectomy between 1992 and 1996. DNA was extracted from archival prostate tissue uninvolved with cancer and genotyped for 3 polymorphic markers. The effects of genetic variants and clinicopathological variables on prostate enlargement risk were estimated by logistic regression. RESULTS The age adjusted odds ratio estimate of prostate enlargement risk in men with 23 or greater versus 20 or fewer CAG repeats was 0.41 (95% confidence interval 0.19 to 0.89). This risk reduction was consistently found when an alternative prostate enlargement definition and subject restriction were used. No consistent association with prostate enlargement risk was observed for A49T or V89L polymorphisms. CONCLUSIONS Our finding further supports the hypothesis that the shorter CAG repeat length of the androgen receptor gene is related to prostate enlargement.

The Mutational Burden of 5-Methylcytosine

The importance of the epigenetic modification of cytosine (C) to 5-methylcytosine (m 5 C) is discussed in other chapters of this volume. In this chapter, we address the heavy mutational burden induced by the methylation of C at CpG dinucleotides, which is the price that must be paid for having a m 5 C epigenetic system. The mutability of m 5 C to thymine (T) has presumably led to a depletion of the CpG dinucleotide in the mammalian genome over the course of evolution. Furthermore, m 5 C residues, which comprise only about 1% of the human genome, account for about 30% of the base substitution mutations found in genetic disease (Cooper and Yousouffian 1988) and 25% of the mutations found in tumor suppressor genes (Jones et al. 1991; Greenblatt et al. 1994). The mutability of m 5 C was first demonstrated in Escherichia coli. Cytosine bases that were methylated in the E. coli lacI gene were found to be hot spots for spontaneous base substitution mutations, and the hot spots disappeared when the same sites were unmethylated (Coulondre et al. 1978). It was speculated that the reason for this increase was that whereas C deaminates to uracil (U), m 5 C deaminates to T, which is a normal DNA base and therefore inherently more difficult to repair (Duncan and Miller 1980; Shenoy et al. 1987). This mechanism of DNA mutation is unique in that it is not induced by exogenous chemicals and it occurs in nonreplicating DNA. The deamination of m 5 C is a first-order chemical process, which is consistent with the...

Surveillance Neuroimaging to Detect Relapse in Childhood Brain Tumors: A Pediatric Oncology Group Study

PURPOSE To investigate the prognostic significance of surveillance neuroimaging for detection of relapse among children with malignant brain tumors. PATIENTS AND METHODS A historical cohort study examined all children who experienced relapse from 1985 to 1999 on one of 10 Pediatric Oncology Group trials for malignant glioma, medulloblastoma, or ependymoma. RESULTS For all 291 patients (median age at diagnosis, 8.2 years), median time to first relapse was 8.8 months (range, 0.6 to 115.6 months). Ninety-nine relapses were radiographic, and 192, clinical; median time to relapse was 15.7 versus 6.6 months, respectively (P = .0001). When stratified by pathology, radiographic and clinical groups showed differences in median time to relapse for malignant glioma (7.8 v 4.3 months, respectively; P = .041) and medulloblastoma (23.6 v 8.9 months, respectively; P = .0006) but not ependymoma (19.5 v 13.3 months, respectively; P = .19). When stratified by early (< 8.8 months) or late (> or = 8.8 months) time to relapse, 115 early relapses were clinical, and 32, radiographic; for late relapses, 77 were clinical, and 67, radiographic (P = .001). Overall survival (OS) from relapse was significantly longer for radiographic compared with clinical detection (median, 10.8 months; 1-year OS, 46% v median, 5.5 months; 1-year OS, 33%; P = .002), but this trend did not retain significance when analyzed by pathology subgroups. CONCLUSION Surveillance neuroimaging detects a proportion of asymptomatic relapses, particularly late relapses, and may provide lead time for other therapies on investigational trials. During the first year after diagnosis, radiographic detection of asymptomatic relapse was infrequent. A prospective study is needed to formulate a rational surveillance schedule based on the biologic behavior of these tumors.

Changes in Serum Concentrations of β‐Carotene and Changes in the Dietary Intake Frequency of Green‐Yellow Vegetables among Healthy Male Inhabitants of Japan

Serum levels of β‐carotene among 147 healthy male inhabitants were measured twice with an interval of one year in order to determine the relationship between changes in serum β‐carotene levels and changes in the dietary intake of green‐yellow vegetables. A positive association was found to exist between changes in the intake frequency of green‐yellow vegetables and changes in serum β‐carotene levels, whereas changes in alcohol intake and smoking were discovered to be negatively associated with changes in serum β‐carotene levels. The positive association between changes in the intake frequency of green‐yellow vegetables and changes in serum β‐carotene levels was preserved after adjustment for these negative factors.

ABO blood type, Lewis and Secretor genotypes, and chronic atrophic gastritis: a cross-sectional study in Japan

Abstract.Background: The H type I structure, synthesized by the secretor (Se) enzyme in gastric foveolar cells, and its metabolite, Lewis b (Leb) antigen, mediate the adhesion of Helicobacter pylori (H. pylori) to the gastric epithelium, whereas H. pylori does not bind to modified forms of Leb specific for blood types A and B. Such host factors as Le and Se genotypes and ABO blood type may affect the establishment of H. pylori infection and, once infected, the risk of chronic atrophic gastritis.Methods: We investigated the cross-sectional relation of ABO blood type and Le and Se genotypes to gastric atrophy, assessed by serum pepsinogen levels, in Japanese residents from two sources.Results: Among the 151 H. pylori-positive participants of the H. pylori eradication program, odds ratios (ORs) for gastric atrophy, adjusted for age, sex, and smoking, were elevated for blood types A (OR = 5.35; 95% confidence interval (CI), 2.11–13.58) and B (OR = 4.79; 95% CI, 1.77–12.93) relative to type O. ORs for blood types A and B were also elevated in H. pylori-negative subjects. These associations were not observed among 250 H. pylori-positive health check-up examinees. The Le genotype was not associated with gastric atrophy in either study population. The se/se genotype was associated with statistically nonsignificant elevation of gastric atrophy risk in both populations.Conclusions: The present data showed a strong association of blood types A and B with gastric atrophy in one, but not the other, study population. Discrepant results between the two populations warrant further investigation.

Validation of a screening protocol for identifying low‐risk candidates with type 1 diabetes mellitus for kidney with or without pancreas transplantation

Abstract: Background: Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post‐transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high‐risk transplant candidates.

Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese.

Abstract.Background:In our previous study, a marked association between Helicobacter pylori seropositivity and functional polymorphisms of the secretor and Lewis genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14–0.70 for se/se genotype relative to Se/Se genotype; and OR, 10.3; 95% CI, 3.16–33.8 for high-risk group defined by the combination of Se and Le relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC) undergoing gastroscopy at Aichi Cancer Center Hospital.Methods:The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city.Results: The associations between H. pylori seropositivity and the Se and Le genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00–2.32 for se/se genotype relative to Se/Se genotype; and OR, 0.77; 95% CI, 0.43–1.40 for the high-risk group defined similarly to the previous study), and among the HCE (OR, 1.25; 95% CI, 0.75–2.07; and OR, 1.07; 95% CI, 0.50–2.26, respectively). The discrepancy between the previous and present results was not explained by the difference in the distributions of age, sex, smoking, and H. pylori seroprevalence.Conclusion:Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important to understand the whole picture of the association under study.