Yasuko Nagao

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.

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)

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.

Relationship between Mammographic Density and the Risk of Breast Cancer in Japanese Women: A Case-Control Study

BackgroundThe relationship between mammographic density and the risk of breast cancer was examined in Japanese women. The study was a matched case-control study comparing the mammographic densities of both breast cancer cases and healthy controls.Materials and MethodsWe selected 237 women who were diagnosed with a histologically verified breast cancer, and who underwent surgery at Gihoku General Hospital in Gifu, from January, 1998 to December, 1999. During the time of this study, 3,650 people participated in breast cancer screening with mammography and ultrasound together. We selected 742 women as a control group from the screening participants and matched them by age and the number of deliveries with the cancer patients. The same mammography machine was used for both cases and controls. For evaluation, we used a visual method (Wolfe’s classification) and a computer assisted method to classify the mammograms based on mammographic density.Results1 According to Wolfe’s classification, the DY group had a significantly increased breast cancer risk compared with the N1 group (Relative risk (RR) = 2.20, 95%confidence interval (95%CI) (1.02-4.77). 2 The group showing a high mammographic density had a significantly increased risk of breast cancer compared with the group with low mammographic density (RR = 2.83, 95%CI = 1.33-5.98) as classified by the computer assisted method.ConclusionIt is suggested that women with high mammographic densities, classified visually or by computer, have an elevated risk of breast cancer compared with those with low mammographic densities.

A case of muscular hamartoma of the breast

We describe a 74-year-old female presenting with a right breast mass. She had found the mass on self-examination. Physical examination revealed a 2.2×2.5 cm, firm, smooth, and mobile lump in the upper medial portion of the right breast.Mammmography revealed a well marginated, oval-shaped, and isodense nodule. Calcification was not evident. On ultrasonography, the lesion was 17×18× 9 mm and located 5 mm below the overlying skin. Excisional biopsy under local anesthesia was performed. The tumor was easily excised. Histopathologically, the lesion was composed of intersecting bundles of spindle-shaped smooth muscle cells, and involved peripheral ducts and fat tissue. Immunohistochemical staining showed positivity for α-smooth muscle actin (SMA), but was negative for S-100 protein, myoglobin, keratin, and vimentin.From these findings a muscular hamartoma of the breast, a rare subtype of hamartoma, was diagnosed.

Sleep duration, nightshift work, and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women

ABSTRACT It has been hypothesized that disruption of circadian rhythms affects human health. Shift work and sleep deprivation are thought to disrupt the normal light–dark cycle, although the disruption due to shiftwork may be dependent on sleep deprivation. Both conditions have been suggested to be associated with an increased risk of cardiometabolic disorders. Non-photic environmental factors, such as the timing of eating, are also thought to regulate circadian rhythm and thus, may have effects on health, but the evidence from human studies is scarce. Oxidative stress is a risk factor of cardiometabolic disorders. Some laboratory studies suggest an involvement of circadian clock genes in the regulation of the redox system. The present study aimed to examine the association of sleeping habits, nightshift work, and the timing of meals with urinary levels of 8-isoprostane, a marker of oxidative stress, and 6-sulfatoxymelatonin, the principal metabolite of melatonin. Study subjects were 542 women who had previously attended a breast cancer mass screening in a community in Japan. Information on bedtimes and wake-up times, history of nightshift work, and the timing of meals was obtained by a self-administered questionnaire. The 8-isoprostane and 6-sulfatoxymelatonin were measured using the first morning void of urine and expressed per mg of creatinine. The geometric mean of 8-isoprostane levels was 12.1% higher in women with ≤6 hours of sleep than that in those with >8 hours of sleep on weekdays, and longer sleep duration on weekdays was significantly associated with lower urinary levels of 8-isoprostane after controlling for covariates (p for trend = 0.04). Women who were currently working the nightshift had a 33.3% higher geometric mean of 8-isoprostane levels than those who were not working nightshift (p = 0.03). Urinary 6-sulfatoxymelatonin levels were unrelated to sleep habits or nightshift work. Women who ate breakfast at irregular times had a 19.8% higher geometric mean of 8-isoprostane levels than those who ate breakfast at a regular time or who did not eat (p = 0.02). Women who ate nighttime snacks at irregular times had a 16.2% higher geometric mean of 8-isoprostane levels than those who did not eat nighttime snacks or who ate nighttime snacks at a regular time (p = 0.003). Among women who ate dinner at a regular time, earlier times for dinner were associated with higher 8-isoprostane and 6-sulfatoxymelatonin levels (p values for trends were 0.01 and 0.02, respectively). However, the times of dinner and nighttime snack are overlapping, and the time of last meal of the day was not associated with 8-isoprostane and 6-sulfatoxymelatonin levels. The time of breakfast or lunch was not associated with these biomarkers among women who ate the meal at regular times. Disturbing the rhythmicity of daily life may be associated with oxidative stress.

Urinary 6-sulfatoxymelatonin and mammographic density in Japanese women.

A protective role of melatonin in the etiology of breast cancer has been suggested. The down-regulation of estrogen secretion by melatonin is thought to be a main cause of the link between melatonin and breast cancer risk. The present cross-sectional study examined whether the urinary 6-sulfatoxymelatonin (aMT6-s) level is inversely associated with mammographic density, which is regarded as a marker of breast cancer risk. The study subjects were 289 Japanese women (175 premenopausal and 123 postmenopausal women) who were recruited from participants in a mammographic breast cancer screening. The size of the total breast area and that of the dense area were measured quantitatively using an automated mammographic mass detection method. The concentration of aMT6-s was measured using first-void morning urine. In premenopausal women, the urinary aMT6-s level was significantly positively associated with percent density after controlling for covariates (P for trend = 0.02). There was no significant association between urinary aMT6-s level and the percent density in postmenopausal women. We found no evidence that the melatonin level is inversely associated with mammographic density. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2509–12)