Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations.

BACKGROUND & AIMS: To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. METHODS: Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. RESULTS: Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. CONCLUSIONS: High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

Waterpipe Tobacco Smoking and Gastric Cancer Risk among Vietnamese Men.

BACKGROUND: The association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested. METHODS: A hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003-2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models. RESULTS: The group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4-0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3-2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2-6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2-11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk. CONCLUSION: The present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men.

Life expectancy and healthy life expectancy of Japan: the fastest graying society in the world.

BACKGROUND: We appraised time trends of Japanese life expectancy (LE) and healthy life expectancy (HALE) by gender, LE-HALE and (LE-HALE)/LE figures, along with the women-men's differences. METHODS: Using the Japanese LE and HALE values from 1990 through 2013 by gender in the article by the GBD 2013 DALYs and HALE Collaborators, we examined trends of LE and HALE, and their 5- or 3-year changes. We also probed LE-HALE and (LE-HALE)/LE values, and the women-men's differences. RESULTS: LE consistently elongated as reported 76.0, 76.5, 77.6, 78.7, 79.3 and 80.1 years for men from 1990 to 2013; and 82.0, 82.8, 84.3, 85.5, 86.1 and 86.4 years for women, respectively. Both time trends demonstrated a significant linear increase (p for trend < 0.001). LE changes were 0.4, 1.1, 1.1, 0.7 and 0.7 years for men, and 0.9, 1.5, 1.2, 0.6 and 0.3 years for women. The trends were statistically significant (p < 0.001), except for 2010-2013 partly due to 3-year interval. HALE also steadily lengthened as seen 68.1, 68.4, 69.1, 69.9, 70.8 and 71.1 years for men from 1990 through 2013; and 72.2, 72.9, 74.0, 74.8, 75.4 and 75.6 years for women. Both time trends showed almost a linear increase (p < 0.05). HALE changes were 0.4, 0.6, 0.8, 0.9 and 0.3 years for men, and 0.7, 1.0, 0.8, 0.6 and 0.2 years for women, without statistical significant trends. LE-HALE values were 8.0, 8.0, 8.5, 8.8, 8.6 and 8.9 years for men; and 9.7, 9.9, 10.4, 10.7, 10.7 and 10.8 years for women. (LE-HALE)/LE figures were 10.5, 10.5, 10.9, 11.1, 10.8 and 11.2% for men, and 11.9, 12.0, 12.3, 12.5, 12.4 and 12.5% for women. LE women-men's differences were 5.9, 6.4, 6.8, 6.8, 6.8 and 6.3 years, and the HALE figures were 4.2, 4.5, 4.9, 4.9, 4.6 and 4.5 years. CONCLUSIONS: LE and HALE consistently linearly elongated for both sexes over the study period. Not only LE-HALE but also (LE-HALE)/LE values were still growing for both sexes. Public health measures, nursing-care/services as well as social security schemes are called for to further elevate longevities, HALE in particular, and enhance quality of life and well-being.

Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening.

The discoveries and application of prostate-specific antigen (PSA) have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa) patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (∼30%). There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1) adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2) improving test performance using doubling time, density, and ratio of free: total PSA; and 3) fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1) examinations of cell proliferation and cell cycle markers in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally, considering the uncertainty that exists in medicine, risk communication on PSA-based screening is indeed due.

Changes in blood biochemical markers before, during, and after a 2-day ultramarathon.

We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker - triglyceride - decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries.

Rare Helicobacter pylori Infection May Explain Low Stomach Cancer Incidence: Ecological Observations in Bali, Indonesia.

The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be strikingly lower than that in Japan. We conducted an on-site ecological study to investigate the association between the stomach cancer incidence and Helicobacter pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155 women) from the general population in Bali, Indonesia, we conducted a urea breath test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect chronic atrophic gastritis and urine analysis to estimate sodium and potassium excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and 7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0-3) for men and 3% (0-5) for women, significantly lower than the respective values in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4) for women, also significantly lower than the Japanese figures. Computed values for daily salt excretion were 13.3±4.1 g (mean ± SD) for men and 11.1±3.1 g for women, as high as corresponding Japanese consumption values. Moreover, the estimated potassium excretion was 3.2±0.7 g for men and 2.8±0.6 g for women in Bali, significantly higher than the figures in Japan. There were no associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be due to the rare H. pylori infection. Namely, the bacterium infection seems to be a critical factor for gastric cancer rather than host or other environmental factors.

Dietary n-3/long-chain n-3 polyunsaturated fatty acids for prevention of sporadic colorectal tumors: a randomized controlled trial in polypectomized participants.

To address preventive effects of n-3 PUFAs/LC n-3 PUFAs on CRTs, a randomized controlled trial was conducted. One-hundred four experimental group participants were advised to increase intake of n-3 PUFAs, including fish/shell fish, fish oil supplements and perilla oils, and to decrease consumption of n-6 PUFAs and fats/oils as a whole for 24 months. One-hundred one control group participants were only cautioned to reduce consumption of fats/oils as a whole. Random allocation was satisfactorily attained, and participants sufficiently complied with our regimen. Intakes, plasma concentrations, and compositions of the RBC and sigmoid colon membranes of n-3 PUFAs, LC n-3 PUFAs, EPA and DHA increased, and the ratios of n-6 PUFAs/n-3 PUFAs and AA/LC n-3 PUFAs decreased without any adverse response. Twenty-four months after the intervention, the multivariate-adjusted hazard ratio (95% confidence intervals) was estimated to be 0.805 (0.536-1.209) with a signal towards the reduced CRT incidence.

The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial.

OBJECTIVE: To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. DESIGN: A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. PARTICIPANTS: 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. RESULTS: The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were non-smokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in non-smokers was 0.37 (CI 0.21 to 0.68, p<0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. CONCLUSIONS: Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. THE CLINICAL TRIAL REGISTRY WEBSITE AND THE CLINICAL TRIAL NUMBER: http://www.umin.ac.jp (number UMIN000000697).

Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial.

There are several reports of clinical trials of aspirin in sporadic colon cancer. However, only one double-blind trial of aspirin in patients with familial adenomatous polyposis (FAP) has been reported to date. This double-blind, randomized, placebo-controlled clinical trial was therefore performed to evaluate the influence of low-dose aspirin enteric-coated tablets (100 mg/day for 6-10 months) in 34 subjects with FAP (17 each in the aspirin and placebo groups). The increase in mean diameter of colorectal polyps tended to be greater in the placebo group compared with the aspirin group, which showed a response ratio, that is, aspirin response rate (number of subjects with reduced polyps/total)/placebo response rate (number of subjects with reduced polyps/total), of 2.33 (95% confidence interval: 0.72-7.55). Subgroup analysis revealed that the number of subjects with a mean baseline polyp diameter of ≤2 mm, and the diameter and number of polyps after intervention showed a significant reduction in the aspirin group. Adverse effects of aspirin, such as anastomotic ulcer, aphtha in the large intestine, and progression of anemia, occurred in three subjects. Moreover, none of the subjects developed colorectal cancer. The results thus indicated a potential for aspirin to reduce colorectal adenoma development in patients with FAP, but careful follow-up is needed to avoid or rapidly counter severe adverse effects.

Usual dietary intakes of selected trace elements (Zn, Cu, Mn, I, Se, Cr, and Mo) and biotin revealed by a survey of four-season 7-consecutive day weighed dietary records in middle-aged Japanese dietitians.

We aimed to identify food sources of selected trace elements (Zn, Cu, Mn, I, Se, Cr, Mo) and biotin in the Japanese diet and to assess usual dietary intakes based on the ratios of within-person to between-person variance. Subjects were 98 middle-aged dietitians living in central Japan who participated in a survey of four-season 7 consecutive day weighed diet records. Based on the latest Standard Tables of Food Composition in Japan published in 2010, food sources of selected nutrients were located according to a contribution analysis, and computed usual dietary intakes. Dietary intakes were checked with the Dietary Reference Intakes for Japanese 2010. Prevalence of inadequacy in a group was determined using the Estimated Average Requirement cut-point method. The major contributors to selected trace elements and biotin were not only meat and milk, but also traditional Japanese food items, including rice, tofu and tofu products, fish, seaweed, chicken eggs, fermented soy bean seasonings, and green tea. Medians of usual intakes were estimated for Zn (men 8.9 mg, women 8.4 mg), Cu (1.32 mg, 1.21 mg), Mn (3.73 mg, 3.76 mg), I (312 µg, 413 µg), Se (97 µg, 94 µg), Cr (10 µg, 9 µg), Mo (226 µg, 184 µg), and biotin (51.7 µg, 47.6 µg). The prevalence of inadequacy of dietary intakes was high for Zn, Cu and Cr. Regarding I, the proportion above the Tolerant Upper Level was overestimated based on the crude mean value. We first identified food sources of selected trace elements and biotin in the Japanese diet, and assessed the usual intakes.

Relationship of living conditions with dietary patterns among survivors of the great East Japan earthquake.

BACKGROUND: During the year after the Great East Japan Earthquake on March 11, 2011, the health conditions and lifestyles of survivors were extensively surveyed. We examined the relationship between living conditions and dietary pattern among survivors. METHODS: A total of 10 466 survivors aged 18 years or older (25% of the population of that age in the area) participated in a survey of Iwate Prefecture. The average frequency of daily consumption of 8 food groups was determined by questionnaire. After excluding staple foods, which were consumed 3 times a day by 85% of participants, factor analysis was performed on 7 food groups among 9789 people (3795 men, 5994 women). RESULTS: Factor analysis identified 2 dietary patterns-prudent and meat. The prudent dietary pattern is characterized by high intakes of fish and shellfish, soybean products, vegetables, fruit, and dairy products and was more evident among older participants and women. The meat dietary pattern is characterized by high intakes of meat and eggs and was more evident among younger participants and men. Age-adjusted multiple logistic regression analyses showed that male and female current smokers and men and women living in difficult conditions were likely to have a lower prudent dietary pattern score; male current smokers and male daily alcohol drinkers were likely to have a higher meat dietary pattern score. CONCLUSIONS: During the year after the earthquake, the prudent dietary pattern was associated with better living conditions among survivors, whereas the meat dietary pattern was not.

[Validity and reproducibility of a physical activity questionnaire used for health surveying among victims of the Great East Japan Earthquake].

OBJECTIVES: This study was performed to assess the validity and reproducibility of a questionnaire on physical activity status used for health surveying among victims of the Great East Japan Earthquake. METHODS: Seventy-four residents (21 men and 53 women) living in temporary housing in Kamaishi City, Iwate Prefecture, participated in this study. The physical activity status questionnaire was composed of 4 questions regarding the frequency of performing domestic and occupational physical activities, the frequency of leaving their residence, walking duration per day, and sedentary time. The physical activity level for 2 weeks was measured using a tri-accelerometer to validate the responses to the questionnaire. Test-retest reproducibility was examined at 2-week intervals. RESULTS: The physical activity levels were 4,521 +/- 2,266 steps/day for men and 4,533 +/- 2,070 steps/day for women. There was a significant difference in step count between those responding differently to the 3 options in the questionnaire regarding average walking duration per day: those who reported walking for > or = 60 min, 30-60 min, or < or = 30 min had step counts of 5,343 +/- 1,757, 4,760 +/- 1,752, and 3,063 +/- 1,772 steps/day, respectively (P < 0.05). When the response options for 3 questions (excluding those for sedentary time) were given scores (a higher score for a higher physical activity level), there were significant correlations between question score and step count (r = 0.486, P < 0.05) and the amount of moderate to vigorous physical activity (r = 0.342, P < 0.05). The test-retest trial showed a moderate degree of reproducibility, with weighted K coefficients of 0.41-0.65. CONCLUSION: Three questions on physical activity levels may allow assessment of an individual's physical activity level, with a moderate degree of reproducibility.

Ovarian cancer mortality among women aged 40-79 years in relation to reproductive factors and body mass index: latest evidence from the Japan Collaborative Cohort study.

OBJECTIVE: This study mainly aimed to investigate the association of ovarian cancer mortality with reproductive factors and body mass index among Japanese women aged 40-79 years. METHODS: The source of the data was the Japan Collaborative Cohort (JACC) study which covered the period of 1988 to 2009. A representative sample of 64,185 women was used. Cox model was used to estimate the relative risk (RR) and 95% confidence interval (CI). RESULTS: The total number of ovarian cancer deaths was 98, with a mortality rate of 9.30 per 100,000 person-years. Women with single marital status revealed significantly higher age-adjusted RR (RR, 4.11; 95% CI, 1.66 to 10.23; p=0.005) as compared to married women. The effect of single marital status was stronger among older women aged 50+ years (RR, 4.58; 95% CI, 1.65 to 12.72; p=0.003) than younger women. An elevated risk was found for both nulliparous and nullipregnant women. Similarly, an increased risk of ovarian cancer mortality was estimated among overweight among aged 50 years or less. CONCLUSION: Out of many factors only single marital status indicated a higher risk for ovarian cancer mortality. All other factors provided inconclusive results, which imply further epidemiological investigations.

Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

Obesity/weight gain and breast cancer risk: findings from the Japan collaborative cohort study for the evaluation of cancer risk.

BACKGROUND: We analyzed data from the Japan Collaborative Cohort Study (36 164 women aged 40-79 years at baseline in 1988-1990 with no previous diagnosis of breast cancer and available information on weight and height) to examine the association between baseline body mass index (BMI)/weight gain from age 20 years and breast cancer risk in a non-Western population. METHODS: The participants were followed prospectively from enrollment until 1999-2003 (median follow-up: 12.3 years). During follow-up, breast cancer incidence was mainly confirmed through record linkage to population-based cancer registries. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs for the association between breast cancer risk and body size. RESULTS: In 397 644.1 person-years of follow-up, we identified 234 breast cancer cases. Among postmenopausal women, the adjusted HR increased with BMI, with a significant linear trend (P < 0.0001). Risk was significantly increased among women with a BMI of 24 or higher (HR: 1.50, 95% CI: 1.09-2.08 for BMI of 24-28.9, and 2.13, 1.09-4.16 for BMI ≥ 29) as compared with women with a BMI of 20 to 23.9. Weight gain after age 20 years and consequent overweight/obesity were combined risk factors for postmenopausal breast cancer risk. This combined effect was stronger among women aged 60 years or older. However, the HRs were not significant in premenopausal women. CONCLUSIONS: Our findings support the hypothesis that weight gain and consequent overweight/obesity are combined risk factors for breast cancer among postmenopausal women, particularly those aged 60 years or older.