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Minami Y.,Tohoku University | Nishino Y.,Miyagi Cancer Center Research Institute | Kawai M.,Tohoku University | Kakugawa Y.,Miyagi Cancer Center Hospital
Cancer Causes and Control

Objective: Being breastfed in infancy has been hypothesized to influence subsequent breast cancer risk. In a hospital-based case-control study, we investigated the relationship between having been breastfed and breast cancer risk, both overall and separately among female subjects with different birth years. Methods: The study subjects included 571 cases and 2,155 controls admitted to a single hospital in Miyagi Prefecture, Japan, between 1997 and 2005. History of having been breastfed was assessed with a self-administered questionnaire. Odds ratios (ORs) and 95% confidence interval (CI) were estimated using logistic regression. Results: After adjustment for known risk factors, no association for having been breastfed was observed overall (OR = 1.20; 95% CI: 0.82-1.76). Analysis stratified according to birth year (<1950, ≥1950) demonstrated heterogeneity in the association for having been breastfed between the two birth-year groups (p for interaction = 0.0006); having been breastfed was significantly associated with a decreased risk among subjects who were born before 1950 (OR = 0.59; 95% CI: 0.35-0.99), whereas no such risk reduction was observed for subjects born after 1950 (OR = 1.60; 95% CI: 0.88-2.90). Conclusion: Although having been breastfed is not related to overall risk, birth year may modify the association between having been breastfed in infancy and breast cancer risk. In Japan, sociodemographic changes have occurred since the end of World War II. The use of standard formula supplement began to spread around 1950. The difference of breast cancer risk between birth-year groups may be attributable to these environmental changes. © 2011 Springer Science+Business Media B.V. Source

Fujii R.,Tohoku University | Hanamura T.,Tohoku University | Suzuki T.,Tohoku University | Gohno T.,Tohoku University | And 10 more authors.
Journal of Steroid Biochemistry and Molecular Biology

breast carcinoma. However, resistance to AI is sometimes acquired, and the molecular mechanisms underlying such resistance are largely unclear. Recent studies suggest that AI treatment increases androgen activity during estrogen deprivation in breast carcinoma, but the role of the androgen receptor (AR) in breast carcinoma is still a matter of controversy. The purpose of this study is to examine the potential correlation between the AR- and AI-resistant breast carcinoma. To this end, we performed immunohistochemical analysis of 21 pairs of primary breast carcinoma and corresponding AI-resistant recurrent tissue samples and established two stable variant cell lines from ER-positive T-47D breast carcinoma cell line as AI-resistance models and used them in in vitro experiments. Immunohistochemical analysis demonstrated that the expression of prostate-specific antigen (PSA) and Ki-67 were significantly higher and ER and progesterone receptor (PR) were lower in recurrent lesions compared to the corresponding primary lesions. Variant cell lines overexpressed AR and PSA and exhibited neither growth response to estrogen nor expression of ER. Androgen markedly induced the proliferation of these cell lines. In addition, the expression profile of androgen-induced genes was markedly different between variant and parental cell lines as determined by microarray analysis. These results suggest that in some cases of ER-positive breast carcinoma, tumor cells possibly change from ER-dependent to AR-dependent, rendering them resistant to AI. AR inhibitors may thus be effective in a selected group of patients. © 2014 Elsevier Ltd. All rights reserved. Source

Shiga K.,Iwate Medical University | Ogawa T.,Tohoku University | Katagiri K.,Iwate Medical University | Yoshida F.,Tohoku University | And 3 more authors.
Oncology Letters

In order to elucidate differences between oral cancers and cancers of the pharynx and larynx, we investigated the genetic and epigenetic changes in these tumors using molecular biology methods. Methylation of the promoter region of the p16 tumor suppressor gene was examined using methylation-specific polymerase chain reaction in specimens from 47 oral, 39 pharyngeal and 35 laryngeal squamous cell carcinomas. These specimens were also characterized for allelic loss of certain areas of the genome, i.e., 3p22, 9p21 and 17p13 (TP53). The frequency of methylation of the promoter region of the p16 gene in tongue cancers (35.3%) was significantly higher than in pharyngeal (12.8%) and laryngeal cancers (11.4%) (p=0.046 and p=0.039, respectively). The frequency of methylation in tumors of female patients (47.1%) was significantly higher compared to tumors of male patients (15.4%) (p=0.0067). In contrast, the frequency of the loss of heterozygosity (LOH) at 3p21 in pharyngeal cancers (66.7%) was significantly higher than in oral cancers (20.0%) (p=0.0006). The frequencies of LOH at 17p13 in pharyngeal (71.0%) and laryngeal cancers (73.1%) were also significantly higher than in oral cancers (36.1%) (p=0.009 and p=0.009, respectively). Our results indicate that there are marked differences in the frequencies of the hypermethylation of genes and allelic loss between oral cancers and cancer of the pharynx and larynx. Although all of these tumors were diagnosed as squamous cell carcinomas, the process of carcinogenesis may be different in tumors located in various parts of the head and neck. Loss of function of tumor suppressor genes by allelic loss gives rise to tumors in the pharynx and larynx, while loss of function due to methylation of the promoter regions of those genes is related to carcinogenesis in the oral cavity. Source

Kawai M.,Tohoku University | Minami Y.,Tohoku University | Kakizaki M.,Tohoku University | Kakugawa Y.,Miyagi Cancer Center Hospital | And 4 more authors.
Breast Cancer Research and Treatment

Alcohol consumption is known to be a risk factor for breast cancer in Western countries, but few epidemiologic data have been available in Japan. This population-based prospective cohort study evaluated the associations of alcohol consumption with breast cancer risk in a Japanese population. A total of 19,227 women aged 40-64 years were followed from 1990 to 2003. During 246,703 person-years of follow-up, 241 breast cancer cases were identified. Hazard ratios (HRs) were estimated by the Cox proportional-hazard regression model. After adjustment for potential risk factors of breast cancer and nutritional factors, the HR and 95% confidence interval (CI) for current drinkers was 1.00 (0.74-1.34) compared with never drinkers. According to the amount of alcohol intake per day, a higher amount (∼15.0 g/day) had no significant relation to breast cancer risk (HR = 0.87, 95% CI: 0.40-1.91; P for trend = 0.85). Age upon starting to drink, and the frequency of drinking, were not associated with breast cancer risk. In analysis stratified according to exogenous female hormone use, a higher alcohol intake (∼15.0 g/day) was associated with an increased risk of breast cancer among hormone users (HR = 1.67, 95% CI: 0.17-16.73); however, this was not statistically significant. Stratification according to folate intake with energy adjustment (<219, ∼219 μg/day) found that breast cancer risk tended to increase with increasing alcohol consumption among women with a low intake of folate (P for trend = 0.09). Our findings suggest that alcohol consumption has no overall effect on breast cancer risk among Japanese women, whereas nutritional factors such as folate intake may modify the alcohol-breast cancer risk relationship. © 2011 Springer Science+Business Media, LLC. Source

Ohuchi N.,Tohoku University | Suzuki A.,Tohoku University | Sobue T.,Osaka University | Kawai M.,Miyagi Cancer Center Hospital | And 13 more authors.
The Lancet

Summary Background Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. Methods Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. Findings Of 72998 women enrolled, 36859 were assigned to the intervention group and 36139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034). Interpretation Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. Funding Ministry of Health, Labour and Welfare of Japan. © 2016 Elsevier Ltd. Source

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