Yoshitomo Kashiki

Association of body mass index, physical activity, and reproductive histories with breast cancer: a case-control study in Gifu, Japan

To further clarify risk factors for breast cancerin Japanese women, a self-administered questionnaire was completedby 157 cases with histologically confirmed breast cancerfrom 1989 to 1993 and by 369 ageand residential area matched controls in Gifu, Japan.Conditional logistic regression model was used to assessthe relations. Multivariate analyses showed that breast cancerrisk decreased with body mass index for premenopausalwomen (RR=0.45; 95% CI=0.22–0.92for BMI ≥ 23 vs. < 21 (kg/m2)),but the risk increased with body mass indexfor postmenopausal women (RR=1.98; 95% CI= 0.86–4.55 for BMI ≥ 24 vs. <21.5 (kg/m2)). The risk increased with a smallnumber of births in pre- and post-menopausal women(1.83; 1.11–2.99 and 6.06; 2.40–15.3 for 1–2 birthsand nulliparity, respectively, vs. ≥ 3 births). Ex-or current smoking increased the risk of breastcancer (2.31; 1.19–4.49). Reduced risk of premenopausal breastcancer was associated with high energy expenditure inphysical activity during teenage, although the trend wasnot statistically significant.

Tumor growth rate and prognosis of breast cancer mainly detected by mass screening.

To investigate the relationship between the tumor growth rate of the primary breast cancer and its prognosis, records for 122 breast cancer patients in 9 hospitals in Japan were retrospectively reviewed. These records contained at least two measurements of the same tumor mass in the breast. So the growth rate was estimated from these measurements taken at different points in time. The doubling time of the breast tumors showed an approximately log‐normal distribution. The geometric mean of doubling times for all cases was 174 days. The solid‐tubular histologic type of carcinoma had the shortest geometric mean of doubling time (126 days), the scirrhous carcinoma had the second shortest one (205 days), and the papillotubular carcinoma had the longest one (252 days). The patients with shorter doubling time of tumor tended to have a poorer prognosis. The Cox multiple regression analysis showed that the tumor growth rate was related significantly with survival, after adjusting for other covariates such as clinical stage, lymph node metastasis, age of patient, histological type, and year of treatment.

Mammographic density and the risk of breast cancer in Japanese women

Using an automated method for detecting mammographic mass, the authors evaluated the relation between quantitatively measured density and the risk of breast cancer in a case–control study among Japanese women. The case subjects were 146 women newly diagnosed and histologically confirmed with breast cancer at a general hospital. A total of 659 control women were selected from those who attended a breast cancer mass screening at this hospital. Significantly increased odds ratios (ORs) of breast cancer were observed for breast densities of 25–49 and 50–74%, but not for densities of 75–100% as compared with 0% in premenopausal women after controlling for covariates (ORs=4.0, 4.3, and 1.4, respectively). In postmenopausal women, ORs were significantly increased for breast densities of 25–50% (OR=3.0) and 50–100% (OR=4.2). Total breast area was significantly associated with the risk of breast cancer independent of density percent or dense area in postmenopausal women. These data suggested that mammographic density was associated with the risk of breast cancer in Japanese women as is the case in Caucasian women. However, the associations of the risk of breast cancer with breast size and a high breast density greater than 75%, needs to be confirmed in future studies.

Comparison of mammographic densities and their determinants in women from Japan and Hawaii

Breast cancer incidence increases considerably in women who migrate from Japan to the United States. Based on the hypothesis that mammographic density in healthy mammograms reflects differences in breast cancer risk, we compared mammographic density in 3 groups of women at different levels of risk: Caucasian and Japanese women in Hawaii and Japanese women in Japan. In a cross‐sectional design, pre‐ and postmenopausal women without a history of breast cancer and with a mammogram free of suspicious lesions were recruited in mammography clinics and completed a self‐administered questionnaire. Cranio‐caudal mammograms were scanned into a computer and the densities measured using a computer‐assisted method. Statistical analyses included ANOVA and multiple linear regression. Breast size among women of Japanese ancestry was similar in Hawaii and Japan but 50% smaller than that among Caucasian women. Dense areas were smallest among women in Japan, intermediate among Japanese women in Hawaii and largest among Caucasian women. Percent densities were greater in Japanese women than Caucasian women because of the larger breast sizes in Caucasians. However, percent densities were significantly higher among Japanese women in Hawaii than in Japan. These results indicate that the size of the total breast differs primarily by ethnicity and the size of the dense areas differs mainly by place of residence. Therefore, when comparing ethnic groups with distinct physical proportions, the absolute size of the dense areas appears to be a better measure of breast cancer risk than the relative density.

Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women.

Background: Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer. Methods: We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women. Results: There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (≥3.00 μg/g creatinine) than in those with low urinary cadmium (<2.00 μg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results. Conclusion: Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.

Associations of Mammographic Density with Dietary Factors in Japanese Women

Background: A high percentage of mammographic dense area has been strongly associated with a risk of beast cancer. The present cross-sectional study evaluated the relations of percent density with dietary factors, such as fats, protein, dietary fiber, and soy isoflavones. Methods: Study subjects were 601 (348 premenopausal and 253 postmenopausal) Japanese women who were recruited from a mammographic screening center. The size of the total breast area and the dense area were measured quantitatively using an automated mammographic mass detection method. Intakes of nutrients were estimated with a validated semiquantitative food-frequency questionnaire. Results: The crude means of the percent density were 39.2% and 18.9% in premenopausal and postmenopausal women, respectively. There were no significant associations of any dietary factors with the percent density in premenopausal women. In postmenopausal women, percent density was significantly positively associated with intakes of protein, total fat, and saturated fat after controlling for covariates; the increase in the means of percent density were 7.2%, 5.6%, and 9.2% in the highest versus lowest quartile of intakes for protein, total fat, and saturated fat, respectively (P for linear trend were 0.006, 0.04, and 0.01, respectively). Carbohydrate intake was inversely associated with percent density; the mean of percent density was 6.0% lower in the highest versus the lowest quartile of intake (Ptrend = 0.03). The associations of dietary factors with dense area were very similar to those with percent density. Conclusion: These dietary factors may have implications for the risk of breast cancer in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2877–80)

Light Exposure at Night, Urinary 6-Sulfatoxymelatonin, and Serum Estrogens and Androgens in Postmenopausal Japanese Women

It has been hypothesized that exposure to light at night increases the risk of breast cancer by suppressing the normal nocturnal increase in melatonin production and release, thereby resulting in increased levels of circulating estrogen. We assessed associations among concentrations of serum estrogen and androgen and the principal metabolite of melatonin in urine, 6-sulfatoxymelatonin, and exposure to light at night based on information regarding the sleeping habits and history of graveyard-shift work of 206 postmenopausal Japanese women. Serum estradiol level was significantly higher in women who were not asleep at or after 1:00 a.m. (the approximate time of the melatonin peak) than those who were asleep after controlling for covariates. Significantly increased estrone levels were observed in women who had worked graveyard shift. Serum testosterone and DHEA sulfate were unrelated to sleeping habits and history of graveyard-shift work. Urinary 6-sulfatoxymelatonin was lower in women who were not asleep at or after 1:00 a.m. on weekends than those who were asleep at this time, but the difference was of borderline significance (P = 0.08). There was no significant association between urinary 6-sulfatoxymelatonin and any serum hormone levels. These data suggest that exposure to light at night has implications for the risk of breast cancer in postmenopausal women. However, the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1418–23)

Mass Screening for Breast Cancer: Comparison of the Clinical Stages and Prognosis of Breast Cancer Detected by Mass Screening and in Out-patient Clinics

To establish the criteria for assessing the life‐prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening in 11 regions of Japan were compared with those for matched patients in out‐patient clinics. A total of 728 patients detected by mass screening and 1,450 found in the out‐patient clinics were reviewed. The stage of the disease was Tis or I in 40.9% of the patients detected by mass screening, and 28.7% of those found in the out‐patient clinics. In contrast, stage III was found in 9.3% and 14.6%, respectively, indicating that early stages were significantly more common in the patients detected by mass screening. The overall survival curve for the patients detected by mass screening was compared with that for those found in the out‐patient clinics. The 5‐year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P<0.01), while the 10‐year survival rate was slightly higher in the same group of patients, but the difference from the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self‐examination (BSE) showed a higher survival rate than those who had not conducted BSE.

Association of Vegetable Intake with Urinary 6-Sulfatoxymelatonin Level

Melatonin is present in plants consumed as vegetables; however, only a limited number of vegetables have been tested for melatonin. The antiproliferative, antioxidative, and immunostimulatory effects of melatonin have been reported from laboratory studies. The potential protective effects of vegetable against cancer and cardiovascular disease may be partially attributable to an increased melatonin intake from vegetables. As a first step to test this hypothesis, we evaluated whether vegetable intake is associated with an increased urinary melatonin in 289 community-dwelling Japanese women. Diet, including vegetable consumption, was assessed with a validated 169-item semiquantitative food-frequency questionnaire. Urinary 6-sulfatoxymelatonin (aMT6-s) was measured in the first-void morning urines. There was a significant positive association between vegetable intake and urinary aMT6-s levels. The mean urinary aMT6-s was 16% higher in women with the highest quartile of vegetable intake than it was in those with the lowest quartile of intake. This association may be explained by the melatonin contained in vegetables. However, data should be regarded as preliminary because it is impossible to estimate dietary melatonin intake from vegetables and or from the entire diet because of incomplete data for melatonin in plants.

Dietary and lifestyle correlates of urinary excretion status of equol in Japanese women.

The isoflavone metabolite equol has been identified in urine or blood samples in some but not all humans. In this cross-sectional study, we examined the association between lifestyle, including diet, and the urinary excretion of equol. Study subjects were 419 Japanese women who were recruited from a breast cancer screening center. Each woman responded to a self-administered questionnaire seeking information about health and lifestyle factors. Diet was assessed by a validated semiquantitative food frequency questionnaire. Urinary isoflavones were measured using spot urine samples. Equol was detected in the urine of 84 (20.0%) women. After controlling for covariates, it was found that dairy product intake was significantly lower in those who excreted detectable equol levels in urine than in those who did not. Because equol is derived from daidzein, individuals with low intake of daidzein may produce undetectable levels of equol. To account for this, the study subjects were restricted to 163 women with urinary daidzein levels of 10 nmol/mg creatinine or higher. The association of equol excretion with dairy product intake remained significant. Demographic factors, smoking status, and menstrual and reproductive factors were unrelated to equol excretion. These data suggest that dairy product intake may be associated with the production of equol.