Fish,n − 3 polyunsaturated fatty acids and n − 6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center‐based prospective study

Limited and inconsistent studies exist on the association between the intake of fish, n ? 3 polyunsaturated fatty acids (PUFA) and n ? 6 PUFA and breast cancer. Fish and n ? 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n ? 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n ? 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha‐linolenic acid (ALA)] and n ? 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45–74 years from the Japan Public Health Center‐based prospective study (JPHC study), and during 14.1 years of follow‐up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n ? 3 PUFA and n ? 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n ? 6 was positively associated with the development of ER+PR+ tumors [multivariable‐adjusted HR _Q4 vs. _Q1 = 2.94 (95% CI: 1.26–6.89; p_trend = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable‐adjusted HR _Q2 vs. _Q1 = 0.47 (95% CI: 0.25–0.89; p_trend =0.47)]. While the overall association between the intake of total fish, n ? 3 PUFA and n ? 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n ? 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake.     

Association between plasma 25-hydroxyvitamin D and colorectal adenoma according to dietary calcium intake and vitamin D receptor polymorphism

The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.     

Hereditary factors in Takayasu's disease

In an attempt to provide support for the genetic link theory as related to the etiology of Takayasu's disease, we analyzed simultaneously A, B, and D loci of HLA antigens in 75 Japanese patients with the disease. Serving as control were 128 healthy Japanese. A statistically significant high frequency of BW52 and DHO was confirmed with the levels being 25.6 and 10.4, respectively, in the chi 2 test. A haplotype of A9-BW52-DHO was frequently evident in these patients as compared to the controls, and here also the statistical difference was significant. There appears to be a closer relationship of the gene to BW52 than to DHO. A survey of the homozygote of BW52 revealed 6 of 75 patients with BW52; however, statistically speaking, this rate did not differ from the expected one. Thus, our analysis of HLA illustrates the genetic factors involved in Takayasu's disease. The genes are located between the B and D loci and are closer to BW52 than DHO and these genes have a dominant character.     

Inhibition of peptic ulcer relapse by ranitidine and ecabet independently of eradication of Helicobacter pylori: a prospective,controlled study versus ranitidine

BACKGROUND/AIMS: The recent increase in resistant strains of Helicobacter pylori has become a serious problem. Ecabet is a novel anti-ulcer agent that acts directly on the gastric mucosa, has bactericidal activity, and inhibits adhesion of Helicobacter pylori to the gastric mucosa. These actions result from inhibition of urease and ATPase in Helicobacter pylori, a mechanism distinct from that of antibiotics. METHODOLOGY: Sixty-three patients positive for Helicobacter pylori who had been cured of gastric ulcers and duodenal ulcers were randomly assigned to receive maintenance therapy with ranitidine alone or a combination of ranitidine and ecabet. Ulcer relapse was studied in these patients. RESULTS: The cumulative relapse rates in the ranitidine group and the ecabet plus ranitidine group were respectively, 29.6% and 4.4% after 1 year of treatment and 66.1% and 13.0%, after 2 years. These differences were significant (p = 0.006). Multivariate analysis of factors potentially related to relapse showed that outcome was significantly related only to treatment (p = 0.020) and not to other characteristics, such as age, diagnosis, or sex. CONCLUSIONS: We conclude that maintenance therapy with a combination of ranitidine and ecabet prevents ulcer relapse in Helicobacter pylori-positive patients. Controlled studies comparing ulcer relapse rates between eradication treatment and maintenance therapy with ranitidine and ecabet are awaited.     

Impact of oncogenes in tumor angiogenesis: Mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells

Targeted disruption of the single mutant K-ras allele in two human colorectal carcinoma cell lines (DLD-1 and HCT-116) leads to loss of tumorigenic competence in nude mice with retention of ability to grow indefinitely in monolayer culture. Because expression of the mutant K-ras oncogene in these cell lines is associated with marked up-regulation of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), we sought to determine whether this potent angiogenesis inducer plays a role in K-ras-dependent tumorigenic competence. Transfection of a VEGF₁₂₁ antisense expression vector into DLD-1 and HCT-116 cells resulted in suppression of VEGF/VPF production by a factor of 3- to 4-fold. The VEGF/VPF-deficient sublines, unlike the parental population or vector controls, were profoundly suppressed in their ability to form tumors in nude mice for as long as 6 months after cell injection. In contrast, in vitro growth of these sublines was unaffected, thus demonstrating the critical importance of VEGF/VPF as an angiogenic factor for HCT-116 and DLD-1 cells. Transfection of a full-length VEGF₁₂₁ cDNA into two nontumorigenic mutant K-ras knockout sublines resulted in a weak but detectable restoration of tumorigenic ability in vivo in a subset of the transfectants, with no consistent change in growth properties in vitro. The findings indicate that mutant ras-oncogene-dependent VEGF/VPF expression is necessary, but not sufficient, for progressive tumor growth in vivo and highlight the relative contribution of oncogenes, such as mutant K-ras, to the process of tumor angiogenesis.