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Background: The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women.Methods: A total of 10,106 postmenopausal women aged 40-64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years.Results: Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05).Conclusion: Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk. [ABSTRACT FROM AUTHOR]

It has been postulated that being breastfed in infancy affects not only health status in childhood but also disease risk in adulthood. To investigate the association of being breastfed with the risks of adult colorectal cancer and benign tumor, we conducted a case-control study including 1190 colorectal cancer and 1585 benign tumor cases and 5301 controls, admitted to a single hospital in Miyagi Prefecture, Japan, between 1997 and 2013. History of having been breastfed was assessed using a self-administered questionnaire, and odds ratios (ORs) were estimated using unconditional logistic regression. There was no association between being breastfed and colorectal cancer risk (breastfed versus formula-only fed, OR = 1.21; 95% CI 0.87-1.67). There was also no association with the risk of benign tumor (OR = 1.04). On the other hand, analyses stratified by sex and birth year found heterogeneous associations. Women born after 1950 who had been breastfed tended to have increased risks of colorectal cancer (OR = 1.58) and benign tumor (OR = 1.51) relative to those who had been formula-only fed, although not statistically significant. In men born after 1950, being breastfed was associated with a significantly decreased risk of benign tumor (OR = 0.57; 95% CI 0.33-0.98)., (© 2024. The Author(s).)

Escherichia coli containing polyketide synthase in the gut microbiota (pks + E coli) produce a polyketide-peptide genotoxin, colibactin, and are suspected to play a role in the development of colorectal neoplasia. To clarify the role of pks + E coli in the early stage of tumorigenesis, we investigated whether the pks status of E coli was associated with the prevalence of colorectal neoplasia. This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan included asymptomatic residents aged 40-79 years who underwent screening colonoscopy and provided a stool sample. We identified 543 participants with colorectal neoplasia (22 colorectal cancer and 521 adenoma) as cases and 425 participants with normal colon as controls. The pks status of E coli was assayed using stool DNA and specific primers that detected pks + E coli. The proportion of pks + E coli was 32.6% among cases and 30.8% among controls. Compared with those with pks - E coli, the odds ratio (OR) (95% confidence interval) for participants with pks + E coli was 1.04 (0.77-1.41) after adjusting for potential confounders. No statistically significant associations were observed regardless of tumor site or number of colorectal adenoma lesions. However, stratified analyses revealed increased ORs among participants who consumed cereals over the median intake or vegetables under the median intake. Overall, we found no statistically significant association between pks + E coli and the prevalence of colorectal adenoma lesions among this Japanese cohort. However, positive associations were suggested under certain intake levels of cereals or vegetables., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Introduction: Noninvasive colorectal cancer (CRC) screening methods with higher sensitivity for advanced colorectal neoplasia (ACN) than the fecal immunochemical test (FIT) alone are warranted. This study aimed to elucidate the diagnostic performance of a risk stratification score calculated using baseline individual characteristics and its combination with FIT for detecting ACN., Methods: This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan, included asymptomatic individuals age 40-79 years who underwent both 2-day quantitative FIT and screening colonoscopy. The 8-point risk score, calculated based on age, sex, CRC family history, body mass index, and smoking history, was assessed. Colonoscopy results were used as reference., Results: Overall, 1,191 individuals were included, and 112 had ACN. The sensitivity and specificity of the 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) for ACN were 17.9%-33.9% (4.9%-22.0% for right-sided ACN) and 91.8%-97.6%, respectively. The risk score's c-statistic for ACN was 0.66, and combining the score (cutoff: 5 points) with 1-/2-day FIT (cutoff: 50-200 ng Hb/mL) yielded a sensitivity and specificity for ACN of 46.4%-56.3% (43.9%-48.8% for right-sided ACN) and 76.6%-80.8%, respectively. The specificity of the risk score and FIT combination for all adenomatous lesions was 82.4%-86.4%., Discussion: The 8-point risk score remarkably increased the sensitivity for ACN, particularly for right-sided ACN. Although the specificity decreased, it was still maintained at a relatively high level. The risk score and FIT combination has the potential to become a viable noninvasive CRC screening option.

Background and Aim: Serrated lesions (SLs) have attracted attention as precursors of colorectal cancer (CRC). However, their prevalence, risk factors, and clinical significance have not been satisfactorily elucidated. This study used high-quality colonoscopy data to determine the prevalence of SLs and to identify their risk factors and relationship with synchronous advanced colorectal neoplasia (ACN) in asymptomatic screened individuals., Methods: This study included data for 5218 individuals who underwent first-time screening colonoscopy by highly experienced endoscopists. The relationships between baseline characteristics and the presence of SLs and those between the presence of SLs and synchronous ACN were assessed using the chi-squared test and multivariate logistic regression., Results: The proportions of individuals with SLs and right-sided SLs were 23.3% and 7.6%, respectively. Age, sex, family history of CRC, smoking, and body mass index were significantly related with the presence of SLs, and current smoking was most strongly associated with SLs (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 2.1-3.2). The aOR (95% CI) of the presence of SLs, SLs sized ≥ 10 mm, and right-sided SLs ≥ 5 mm for synchronous ACN was 1.4 (1.1-1.9), 3.5 (1.3-9.6), and 1.9 (1.0-3.8), respectively. The presence of left-sided SLs ≥ 10 mm (without right-sided SLs) was also significantly associated with ACN (aOR 8.1, 95% CI 2.0-33.7)., Conclusions: The relatively high prevalence of SLs and risk factors in screened individuals were elucidated and the significant relationship between SLs, particularly SLs ≥ 10 mm and right-sided SLs ≥ 5 mm, and synchronous ACN was confirmed., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Although intake of highly sugary foods is considered to be a potential risk factor for colorectal cancer through hyperinsulinemia, the association of sugar intake and colorectal adenoma, a precursor lesion to most colorectal cancer, is poorly understood, particularly in Asian populations. We undertook a cross-sectional study in a Japanese population to investigate the association between dietary sugar intake and the prevalence of colorectal adenoma. Study subjects were selected from participants who underwent magnifying colonoscopy with dye spraying as part of a cancer screening program and who responded to a self-administered questionnaire before the colonoscopy. A total of 738 cases with colorectal adenoma and 697 controls were enrolled. Dietary intakes of glucose, fructose, galactose, sucrose, maltose, lactose, and total sugars (sum of these six mono- or disaccharides) were calculated from a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals of colorectal adenoma were estimated using unconditional logistic regression models, with adjustment for potential confounding factors. Total sugar intake was not significantly associated with the prevalence of colorectal adenoma (odds ratio for the highest intake group compared to reference group = 1.18; 95% confidence interval, 0.81-1.73; P for trend = .34). Furthermore, no statistically significant positive associations were observed for any of the six mono- or disaccharides. Findings were similar on additional analyses by site, size, and number of adenomas. Our findings do not support an association between high sugar intake and increased odds ratios of colorectal adenoma., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: It is unclear whether alcohol consumption may impact survival after breast cancer diagnosis. To clarify the association between pretreatment alcohol consumption and survival in breast cancer patients, a prospective patient cohort study was conducted., Methods: The cohort comprised 1,420 breast cancer patients diagnosed during 1997-2013 at a single institute in Japan. Alcohol drinking and other lifestyle factors were assessed by questionnaire survey at the initial admission. The patients were followed until December 31, 2016. The crude associations of pretreatment alcohol intake with survival were evaluated by Kaplan-Meier analysis. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) controlled by confounders., Results: During a median follow-up period of 8.6 years, 261 all-cause and 193 breast cancer-specific deaths were documented. Survival curves showed that ever-drinkers tended to have better survival than never-drinkers (breast cancer-specific survival, log-rank p = 0.0381). Better survival was also observed for light drinkers with an intake of <5.0 g per day. In the Cox model, ever-drinking was associated with a decreased risk of all-cause (HR: 0.75; 95% CI: 0.54-1.05) and breast cancer-specific death (HR: 0.68; 95% CI: 0.46-0.99). Light drinkers had a lower risk of breast cancer-specific death (frequency of drinking, HR = 0.57 for occasional or 1-2 times per week and 0.72 for 3-7 times per week; amount of alcohol consumed per day, HR = 0.57 for <5.0 g and 0.68 for ≥5.0 g compared with never-drinking). In terms of hormone receptor status, a significantly decreased risk of death associated with ever-drinking was observed among women with receptor-negative cancer (ER-/PR-, HR = 0.41; 95% CI: 0.20-0.84 for breast cancer-specific death)., Conclusions: Pretreatment, i.e., pre-diagnosis alcohol consumption is unlikely to have an adverse effect on survival after breast cancer diagnosis. Light alcohol consumption may have a beneficial effect on patient survival., Competing Interests: The authors have declared that no competing interests exist.

Background: Reproductive factors may influence breast cancer progression and patient survival; however, evidence has been limited., Methods: The associations of reproductive factors with tumor characteristics and patient survival were analyzed among 1468 breast cancer patients diagnosed during 1997-2013 at a single institute in Japan. The patients were followed until 2016. During a median follow-up period of 8.6 years, 272 all-cause and 199 breast cancer deaths were documented., Results: In case-case comparisons, later age at menarche was inversely associated with advanced tumors. Nulliparous patients tended to have receptor-positive [estrogen receptor (ER)+ or progesterone receptor (PR)+] tumors. Conversely, the Cox proportional-hazards model including adjustment for tumor characteristics revealed U-shaped relationship between parity number and the risk of all-cause death among the patients overall [hazard ratio (HR) = 2.10 for nulliparous, 1.28 for 2, and 1.50 for ≥ 3 vs. one child]. According to hormone receptor, later age at menarche and later age at last birth were positively associated with the risk of all-cause death among patients with ER- and PR- cancer (menarche, HR = 2.18 for ≥ 15 vs. ≤ 12 years, p trend  = 0.03; last birth, HR = 3.10 for ≥ 35 vs. ≤ 29 years, p trend  = 0.01). A shorter time since last birth was associated with the risk of death among receptor-positive patients (HR = 5.72 for ≤ 4 vs. ≥ 10 years, p trend  = 0.004)., Conclusion: The results indicate that the timing of menarche and parity have significant effects on patient survival, providing clues for understanding the association between women's life course and breast cancer outcome.

Objectives: Because of the increasing number of detected diminutive colorectal adenomas, the "diagnose-and-do-not-resect" approach has recently attracted attention as an alternative to resection. We evaluated the cumulative incidence of advanced colorectal neoplasia (ACN) in individuals with untreated diminutive adenomas and compared this incidence in individuals without adenomas., Methods: Data from 1,378 individuals who underwent first screening colonoscopy (CS) and at least one follow-up CS without polypectomy were analyzed. Patients with no adenomas or with only nonadvanced diminutive adenomas (<5 mm) diagnosed by magnifying image-enhanced endoscopy were scheduled to undergo a follow-up CS within 5 years after the initial CS without treatment. The participants were divided into 2 groups: those with untreated diminutive adenomas (group A) and those with no adenomas (group B). The cumulative incidence of ACN and the hazard ratio were assessed using Gray's test and the Fine and Gray model., Results: During the median follow-up period of 60.9 months, 21 ACNs were detected. The 5-year cumulative incidences of ACN in group A (n = 361) and group B (n = 1,017) were 1.4% (95% confidence interval [CI]: 0.5-3.4) and 0.8% (95% CI: 0.3-1.7), respectively, without a statistically significant difference (P = 0.23). No ACNs developed from unresected adenomas. The smoking status was significantly associated with the incidence of ACN, and the hazard ratio for ACN in group A vs group B adjusted for smoking status was 1.43 (95% CI: 0.52-3.90; P = 0.48)., Discussion: The low 5-year cumulative incidence of ACN suggests the potential to adopt the "diagnose-and-do-not-resect" strategy as an alternative option for diminutive adenomas not requiring excessive surveillance.

Background: Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening., Methods: Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed., Results: ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m 2 , and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of < 3, ≥ 3 to < 5, and ≥ 5, respectively. The c-statistic of the scoring model was 0.70 (95% confidence interval, 0.67-0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]., Conclusions: We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.

Cigarette smoking and alcohol drinking may affect the prognosis of stomach cancer, but evidence has been inconsistent. We investigated the associations between pretreatment smoking and alcohol drinking and the risk of all-cause and stomach cancer death among 1,576 patients with histologically confirmed stomach cancer diagnosed during 1997-2010 at a single hospital in Japan. Histories of smoking and alcohol drinking were assessed using a self-administered questionnaire. The patients were followed until December 31, 2013. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 9,625.1 person-years, 670 all-cause and 419 stomach cancer deaths were documented. Among the patients overall, ever-drinking was significantly associated with an increased risk of all-cause death (HR: 1.25; 95% CI: 1.03-1.51), but not stomach cancer death. Positive linear associations with the frequency of drinking (p trend  = 0.02) and the amount of alcohol consumed per day (p trend  = 0.03) were observed for the risk of all-cause death. Ever-smoking was not related to either the risk of all-cause or stomach cancer death. Conversely, among the patients who underwent curative resection, a significant positive association was found between ever-smoking and the risk of stomach cancer death (HR: 2.44; 95% CI: 1.17-5.08). A positive association was also found for earlier age at start of smoking (p trend  = 0.0046). Pretreatment smoking and alcohol drinking have significant effects on stomach cancer survival. Lifestyle adjustments throughout life may improve survival., (© 2018 UICC.)

Alcohol consumption is a risk factor for breast cancer in Western countries, but few studies have evaluated the risk for Japanese women, who have a relatively low alcohol intake. This case-control study investigated the association of alcohol consumption with breast cancer risk according to estrogen-receptor and progesterone-receptor (ER/PgR) status in Japanese women. From female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2011, 1,256 breast cancer cases (669 ER+/PgR+, 162 ER+/PgR-, 21 ER-/PgR+, 305 ER-/PgR-, and 99 missing) and 2,933 controls were selected. Alcohol-related measures were assessed using a self-administered questionnaire. Unconditional logistic regression analysis was performed. Alcohol-related measures were not associated with breast cancer risk among the women overall. Moreover, no association was observed between ever drinking and the risk of a concordant receptor subtype (ER+/PgR+ or ER-/PgR-). Conversely, ever drinking was inversely associated with the risk of discordant subtype (ER+/PgR-, odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.41-0.95; ER-/PgR+, OR = 0.44, 95% CI: 0.14-1.42). For ER+/PgR-, an inverse association with the amount of alcohol consumed per day was observed (P for trend = 0.04), and this inverse association was limited to premenopausal women. Alcohol consumption may have differential effects on concordant and discordant receptor subtypes of breast cancer. In view of the low frequency of discordant subtype in Japanese women and their relatively low alcohol intake, our findings may provide a clue for elucidating the etiology of breast cancer rather than for preventing discordant subtype.

The utility of capsule endoscopy (CE) for the surveillance of small intestinal lesions in familial adenomatous polyposis (FAP) patients has been reported. However, few studies have investigated the safety of CE in FAP patients who have undergone colon surgery. We aimed to assess the safety of surveillance CE in post-colectomy FAP patients and the endoscopic findings associated with small intestinal lesions. We assessed the safety of CE surveillance of small intestinal lesions in 41 FAP patients who had undergone colectomies. Forty-two CEs were performed in 41 patients at our facility from April 2012 to July 2014. CE was conducted safely and none of the capsules were retained, despite the inclusion of patients who had undergone several abdominal surgeries previously. Thirty-nine out of 42 capsules (93 %) were retrieved within the examination timeframe; hence, the retrieval rate was favorable. The findings from this study indicate that surveillance CE can be safely conducted in post-colectomy FAP patients.

It has long been hypothesized that personality is associated with breast cancer risk and survival. The present population-based prospective cohort study in Japan tested this hypothesis. To investigate the association of personality with breast cancer risk, a total of 15,107 women aged 40-64 years who completed the Eysenck Personality Questionnaire-Revised (EPQ-R) Short Form were followed from 1990 to 2007. To assess the association of personality with survival after breast cancer, 250 identified cases were further followed up from the date of diagnosis to 2008, and 45 all-cause deaths were documented. Study subjects were categorized into four groups based on the quartile points of scores ranging between 0 and 12 on each EPQ-R subscale (extraversion, neuroticism, psychoticism, and lie), and the hazard ratio (HR) for each category was computed using the lowest category as reference. Multivariate analysis revealed no association between any of the four personality subscales and the risk of breast cancer. In the analysis on survival, no significant association was found between any of these subscales and the risk of death, although breast cancer cases with a higher score of extraversion tended to have a lower risk of death (P for trend = 0.07; HR for highest score level = 0.38). Exclusion of 32 cases diagnosed in the first 3 years of follow-up did not largely change the results with regard to either breast cancer risk or survival. The present findings suggest that personality does not impact significantly on the development and progression of breast cancer.

Colonoscopic evaluation of mucosal tissues after allogeneic hematopoietic stem cell transplantation (HSCT) is very useful in evaluating pathogenesis and diagnosis of intestinal graft-versus-host disease (GVHD). However, information on the timing and sites of biopsies and the immunohistological evaluation of mucosal tissues for diagnosing intestinal GVHD, especially following reduced-intensity (RIC) regimens, remains very limited. A total of 33 patients with histologically proven GVHD after allogeneic HSCT with RIC (n = 23) and myeloablative conditioning (MAC, n = 10) regimens were enrolled in the present study. Colonoscopy was performed due to gastrointestinal symptoms, especially diarrhea and anorexia. Sites of biopsies with the worst histopathological grading were the terminal ileum in 67 % of patients. In the RIC group, the onset of diarrhea prior to colonoscopy examination was later (median: RIC, 57 vs. MAC, 27 days) and the number of patients who developed abdominal pain tended to be higher (RIC, 70 % vs. MAC, 30 %). A lower number of CD4+ cells and a higher ratio of Foxp3+ cells to CD4+ cells were detected in the involved lesions of intestinal GVHD following RIC. These differences in the RIC and MAC groups suggest that regimen-specific therapeutic strategies are required for diagnosing intestinal GVHD.

Background: Body mass index (BMI) may be an important factor affecting breast cancer outcome. Studies conducted mainly in Western countries have reported a relationship between higher BMI and a higher risk of all-cause death or breast cancer-specific death among women with breast cancer, but only a few studies have been reported in Japan so far. In the present prospective study, we investigated the associations between BMI and the risk of all-cause and breast cancer-specific death among breast cancer patients overall and by menopausal status and hormone receptor status., Methods: The study included 653 breast cancer patients admitted to a single hospital in Japan, between 1997 and 2005. BMI was assessed using a self-administered questionnaire. The patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to quartile points of BMI categories, respectively: <21.2, ≥21.2 to <23.3 (reference), ≥23.3 to <25.8 and ≥25.8 kg/m2., Results: During the follow-up period, 136 all-cause and 108 breast cancer-specific deaths were observed. After adjustment for clinical and confounding factors, higher BMI was associated with an increased risk of all-cause death (HR = 2.61; 95% CI: 1.01-6.78 for BMI ≥25.8 vs. ≥21.2 to <23.3 kg/m²) among premenopausal patients. According to hormonal receptor status, BMI ≥25.8 kg/m² was associated with breast cancer-specific death (HR = 4.95; 95% CI: 1.05-23.35) and BMI <21.2 kg/m2 was associated with all-cause (HR = 2.91; 95% CI: 1.09-7.77) and breast cancer-specific death (HR = 7.23; 95% CI: 1.57-33.34) among patients with ER + or PgR + tumors. Analysis by hormonal receptor status also showed a positive association between BMI and mortality risk among patients with ER + or PgR + tumors and with BMI ≥21.2 kg/m² (p for trend: 0.020 and 0.031 for all-cause and breast cancer-specific death, respectively)., Conclusions: Our results suggest that both higher BMI and lower BMI are associated with an increased risk of mortality, especially among premenopausal patients or among patients with hormonal receptor positive tumors. Breast cancer patients should be informed of the potential importance of maintaining an appropriate body weight after they have been diagnosed.

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.

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.

The incidence of breast cancer among Japanese women is substantially increasing. This population-based prospective cohort study in Japan evaluated the associations of reproductive factors and exogenous female hormone use with breast cancer risk, both overall and separately among premenopausal and postmenopausal women. A total of 24,064 women aged 40-64 were followed from 1990 to 2003. During 309,424 person-years of follow-up, 285 breast cancer cases were documented. In overall evaluation, nulliparity was significantly associated with an increased risk of breast cancer. There was a significant decrease in risk with increasing parity number among parous women (trend P = 0.008). No association was observed between age at menarche or age at first birth and breast cancer risk. Neither oral contraceptive (OC) use nor the use of exogenous female hormones other than OC was associated with breast cancer risk. The evaluation according to menopausal status revealed that nulliparity and parity number were significantly related to breast cancer risk only among postmenopausal women. Later age at natural menopause was associated with an increased risk of breast cancer among postmenopausal women (trend P = 0.02). Our findings suggest that parity number and age at menopause have great effects on breast cancer risk among Japanese women.