Yoshimitsu Niwa

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan.

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40–79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow‐up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate‐adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46–1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long‐chain n‐3 fatty acids; the RR were 0.56 (95% CI 0.33–0.94) and 0.50 (0.30–0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08‐fold increase in risk (95% CI 1.05–4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long‐chain n‐3 fatty acids that are abundant in fish. (Cancer Sci 2005; 96: 590 – 599)

Prospective clinical study of endoscopic ultrasound-guided choledochoduodenostomy with direct metallic stent placement using a forward-viewing echoendoscope.

A prospective clinical study was conducted to evaluate the safety, feasibility, and efficacy of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with direct metallic stent placement using a prototype forward-viewing echoendoscope. The indication for EUS - CDS in this study was lower biliary obstruction only, and not failed endoscopic biliary drainage, because the aim was to evaluate EUS - CDS for first-line biliary drainage therapy. The technical and functional success rates were 94 % (17 /18) and 94 % (16 /17), respectively. Early complications (focal peritonitis) were encountered in two patients (11 %). No patients developed late complications. EUS - CDS with direct metallic stent placement using a forward-viewing echoendoscope was generally feasible and effective for malignant distal biliary tract obstruction. The forward-viewing echoendoscope was useful, especially for deploying the metallic stent.

Active Smoking, Passive Smoking, and Breast Cancer Risk: Findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk

Background Evidence is lacking regarding the relationship between cigarette smoking and breast cancer in Japanese women. We examined the association between breast cancer incidence and active and passive smoking in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Methods Our study comprised 34,401 women aged 40-79 years who had not been diagnosed previously with breast cancer and who provided information on smoking status at baseline (1988-1990). The subjects were followed from enrollment until December 31, 2001. Cox proportional-hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between breast cancer incidence and tobacco smoke. Results During 271,412 person-years of follow-up, we identified 208 incident cases of breast cancer. Active smoking did not increase the risk of breast cancer, with a HR for current smokers of 0.67 (95% CI: 0.32-1.38). Furthermore, an increased risk of breast cancer was not observed in current smokers who smoked a greater number of cigarettes each day. Overall, passive smoking at home or in public spaces was also not associated with an increased risk of breast cancer among nonsmokers. Women who reported passive smoking during childhood had a statistically insignificant increase in risk (HR: 1.24; 95% CI: 0.84-1.85), compared with those who had not been exposed during this time. Conclusion Smoking may not be associated with an increased risk of breast cancer in this cohort of Japanese women.

Impact of menstrual and reproductive factors on breast cancer risk in Japan: Results of the JACC study

The incidence of breast cancer among Japanese women, a traditionally low‐risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38 159 Japanese women, aged 40–79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow‐up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P = 0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P = 0.05), the association being very apparent among menopausal women (trend P = 0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72–6.21) and 3.33 (1.07–10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women. (Cancer Sci 2005; 96: 57–63)

Coffee consumption and the risk of endometrial cancer: Evidence from a case-control study of female hormone-related cancers in Japan

Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone‐related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone‐related cancer risk among Japanese women using data from the hospital‐based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non‐drinker, the OR of daily drinking of 1–2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43–0.94) and 0.41 (95% CI: 0.19–0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone‐dependent cancer risk, additional investigations are warranted. (Cancer Sci 2007; 98: 411–415)

Relationship between body mass index and the risk of ovarian cancer in the Japanese population: Findings from the Japanese Collaborate Cohort (JACC) study

Aim: The incidence of ovarian cancer in Japan has increased since the 1970s. The many studies that have assessed the relationship between body mass index (BMI) and the risk of ovarian cancer have produced contradictory results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk, which was initiated in 1988.

Psychological attitudes and risk of breast cancer in Japan: a prospective study

ObjectiveTo examine the association between psychological factors and the risk of breast cancer prospectively in a non-Western population.MethodsData from the Japan Collaborative Cohort (JACC) study were analyzed. From 1988 to 1990, 34,497 women aged 40–79 years completed a questionnaire on medical, lifestyle and psychosocial factors. The rate ratios (RRs) of their responses were computed by fitting to proportional hazards models.ResultsDuring the mean follow-up period of 7.5 years, 149 breast cancer cases were documented. Those individuals who possessed “ikigai” (Japanese term meaning something that made one’s life worth living) showed a significantly lower risk of breast cancer (multivariate-adjusted RR = 0.66; 95% confidence interval [CI] = 0.47–0.94). Those who perceived themselves as able to make decisions quickly also had a lower risk of breast cancer (multivariate-adjusted RR = 0.56; 95% CI = 0.36–0.87). The other factors investigated, including ease of anger arousal and self-perceived stress of daily life were not associated with breast cancer risk.ConclusionsAlthough further studies will be necessary to verify these findings, our results suggest that having “ikigai” and being decisive decrease an individual’s subsequent risk of breast cancer.

Role of Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Diagnosing Metastasis to the Pancreas: A Tertiary Center Experience

Background: Metastasis to the pancreas (MP) is a rare entity that is difficult to identify by imaging alone. Few reports have described endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) findings. Herein, we try to describe the EUS and EUS-FNA characteristics of MP. Methods: This retrospective study compared 28 patients with MP (13 males; mean age: 60.1 ± 12.6 years) and 60 control patients (30 males; 62.7 ± 11.5 years) with pancreatic ductal adenocarcinoma (PDAC). All lesions were characterized by EUS, and MP was diagnosed by EUS-FNA (n = 16), surgery (n = 6) or both (n = 6). Results: Multivariate logistic regres- sion revealed that the presence of regular borders (p = 0.004; OR: 8.81, 95% CI: 1.97–39.4), the absence of retention cysts (p = 0.045; OR: 12.5, 95% CI: 1.06–147.0), and the absence of main pancreatic duct (MPD) dilation (p = 0.003; OR: 8.18, 95% CI: 2.04–32.8) were predictors of MP rather than PDAC. The EUS-FNA sampling adequacy was 95.4% (21/22), and the correct diagnosis was obtained in 95.2% (20/21) of cases when K-ras mutation analysis and/or immunostaining were added. Conclusion: The presence of regular borders, the absence of retention cysts and the presence of nondilated MPD on EUS indicate MP rather than PDAC. This diagnosis can be accurately confirmed by EUS-FNA with immunostaining and/or K-ras analysis.

Cigarette smoking and the risk of ovarian cancer in the Japanese population: Findings from the Japanese Collaborate Cohort study

Aim: The many studies into the relation between cigarette smoking and the risk of ovarian cancer have produced inconsistent results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, initiated in 1988.

Oncolytic viral therapy for human ovarian cancer using a novel replication-competent herpes simplex virus type I mutant in a mouse model

OBJECTIVE Attenuated mutant strains of herpes simplex virus (HSV) have been effectively used for treatment of malignant brain tumors. As HSV-1 can infect and lyse a variety of cell types, other malignancies may also benefit from such treatment. We sought to test the feasibility of HSV-1 mutant-mediated gene therapy treatment of ovarian cancer. METHODS We prepared two attenuated mutant HSV-1 strains. An HSV-1 mutant, hrR3, has replaced the gene encoding ribonucleotide reductase (RR) with the lacZ reporter gene. We also developed a new replication-competent HSV-1 mutant, HR522; this virus, expressing the lacZ reporter gene, induces syncytium formation in infected cells. We compared the efficacy of HR522 with, paclitaxel (Taxol) and hrR3 in the treatment of nude mice harboring human ovarian cancer cells. We also examined the effect of the prodrug ganciclovir (GCV) on the treatment mediated by these HSVs. Survival was evaluated by Kaplan-Meier method and log-rank test. RESULTS The survival of mice treated with a high-titer hrR3 (5 x 10(7) plaque-forming units [PFU]) was significantly prolonged as compared with the group given paclitaxel (P < 0.0001, log-rank test). Although the survival of mice treated with high-titer HR522 (5 x 10(7) PFU) was not significantly prolonged compared with paclitaxel-treated group (P = 0.212, log-rank test), GCV markedly enhanced the efficacy of HR522 administration (P < 0.005, vs paclitaxel, log-rank test). The lacZ gene product, visualized using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) histochemistry, was detected in HR522-treated tumors in areas also exhibiting apoptotic changes. CONCLUSIONS These findings indicate that the combination of HR522 and GCV possesses significant therapeutic potential for treatment of ovarian cancer. Such viral therapy offers a novel approach to reductions in the dissemination of ovarian cancer.