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The efficacy of calcium with vitamin D supplementation in preventing hip and other fractures in healthy postmenopausal women remains equivocal. In this Women's Health Initiative trial, 36,282 such women received calcium with vitamin D or placebo, with an average follow-up of seven years. Calcium with vitamin D supplementation moderately but significantly improved hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. In healthy postmenopausal women, calcium with vitamin D supplementation moderately but significantly improved hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. Osteoporosis, a major cause of injury, loss of independence, and death, 1 , 2 contributes to more than 300,000 hip fractures in the United States annually. 3 Observational evidence 4 and data from randomized clinical trials 5 , 6 suggest that calcium or vitamin D supplements or both may slow bone loss 5 , 6 and reduce the risk of falls 7 , 8 in postmenopausal and elderly women. However, evidence from trials, 5 , 9 – 19 observational studies, 20 , 21 and meta-analyses 6 , 22 , 23 of calcium and vitamin D supplementation with respect to hip and other fractures is limited. In two recent randomized trials, calcium plus vitamin D supplements (1000 mg of . . .

Supplemental calcium and vitamin D have been associated with a reduced risk of colorectal cancer in epidemiologic and polyp-prevention studies, but evidence from randomized trials was lacking. Although the long latency involved in colorectal cancer may be relevant, this Women's Health Initiative trial involving 36,282 postmenopausal women showed that daily calcium plus vitamin D supplementation for an average of seven years had no effect on the incidence of colorectal cancer. Although the long latency involved in colorectal cancer may be relevant, this trial involving postmenopausal women showed that daily calcium plus vitamin D supplementation for an average of seven years had no effect on the incidence of colorectal cancer. As the second leading cause of death from cancer in the United States, 1 colorectal cancer is the focus of considerable preventive effort. 2 Most observational studies have associated increased calcium and vitamin D intake with a decreased risk of colorectal cancer 3 – 6 and recurrent polyps. 7 , 8 Although the results are somewhat mixed, one pooled analysis of 10 cohort studies that assessed dietary consumption and total calcium intake (diet plus supplements) reported a reduction in the incidence of colorectal cancer of 10 to 15 percent, 9 whereas an earlier pooled analysis found no effect. 10 The suggestion that increased calcium intake helped prevent colorectal . . .

Recent clinical trials have found that the combination of conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect on the incidence of type 2 diabetes. To determine the effect of CEO alone on the incidence of diabetes mellitus in postmenopausal women, we analysed the results of the Women's Health Initiative oestrogen-alone trial. The Women's Health Initiative is a randomised, double-masked trial comparing the effect of daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739 postmenopausal women who were aged 50-79 years and had previously had a hysterectomy. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin and lipoproteins were measured in an 8.6% random sample of study participants, at baseline and at 1, 3 and 6 years. The cumulative incidence of treated diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow-up, a significant fall in insulin resistance (homeostasis model assessment of insulin resistance) in actively treated women compared with the control subjects (Year 1 baseline between-group difference -0.53) was seen. However, there was no difference in insulin resistance at the 3- or 6-year follow-up. Postmenopausal therapy with oestrogen alone may reduce the incidence of treated diabetes. The effect is smaller than that seen with oestrogen plus progestin. CEO should not, however, be used with the intention of preventing diabetes, as its well-described adverse effects preclude long-term use for primary prevention.

Background:Germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome colon cancers. Less understood is the risk of colon cancer associated with common polymorphisms in MMR genes and the potential interacting role of lifestyle factors known to damage DNA.Methods:A study was conducted to examine whether MLH1 (-93G>A and Ile219Val) and MSH6 (Gly39Glu) polymorphisms were associated with risk of colon cancer in data from 1609 colon cancer cases and 1972 controls. Genotype data were further stratified by microsatellite instability status, smoking, alcohol, Western diet, alcohol and obesity, to investigate potential heterogeneity.Results:The MSH6 39Glu allele was associated with increased risk of colon cancer among men (Gly/Glu or Glu/Glu vs Gly/Gly, OR 1.27; 95% CI 1.04 to 1.54). Neither MLH1 polymorphism was associated with colon cancer risk overall. When stratified by microsatellite stability status, however, the MLH1 -93A allele was associated with a more than doubling in microsatellite instability (MSI)-positive colon cancer risk (AA vs GG, OR 2.47; 95% CI 1.48 to 4.11); no associations were observed between the MMR polymorphisms examined and MSI-negative colon cancer. Statistically significant interactions were observed between: MLH1 -93G>A and smoking (MSI-negative colon cancer only, p value interaction: 0.005); and MLH1 Ile219Val and Western diet (p value interaction: 0.03).Conclusions:The MSH6 Gly39Glu and MLH1 -93G>A polymorphisms were associated with risk of overall colon and MSI-positive colon cancers, respectively. Risk for colon cancer, stratified by MMR genotype, was further modified by smoking and Western diet.

OBJECTIVE: To investigate the risks of height, weight and body fat distribution associated with colon cancer in subcategories of gender, age and site in the colon. Interaction with family history of colorectal cancer is also examined. DESIGN: Case-control study of diet, anthropometry and colon cancer risk. SUBJECTS: Nineteen hundred and eighty-three colon cancer cases (age 30-79 y) and 2400 age and gender matched population controls. MEASUREMENTS: Height, weight and waist and hip circumferences were obtained by trained interviewers. Body Mass Index (BMI) and Waist-Hip Ratio (WHR) were calculated. RESULTS: Of all anthropometric measurements examined, only BMI was consistently associated with an increased risk of colon cancer. The test for trend for BMI was significant for men and women overall and for the majority of subgroups examined. In younger persons those with a family history of colorectal cancer had a greater risk of colon cancer associated with BMI (Men odds ratio (OR) = 7.76, 95% confidence interval (CI) 2.60, 23.1; Women OR = 4.85, 95% CI 2.33, 10.12) comparing the third tertile to the first, than those with no family history (Men OR = 1.70 95% CI 1.25, 2.32; Women OR = 1.53 95% CI 1.22, 1.92). WHR, after controlling for BMI was not associated with colon cancer in men, and was associated with a slight increase in women (primarily in those with distal tumors). CONCLUSION: This study contributes to mounting evidence that excess weight is associated with an increased risk of colon cancer.

Background In the Women’s Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer ( P  = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components. Methods In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P -values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score. Results HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components ( n  = 10,639), HR 1.09, 95% CI 0.63–1.87; with 1–2 MS components ( n  = 30,948), HR 0.80, 95% CI 0.62–1.02; with 3–4 MS components ( n  = 4,246), HR 0.31, 95% CI 0.14–0.69 (interaction P  = 0.01). Conclusions While postmenopausal women with 3–4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk. Registry ClinicalTrials.gov (NCT00000611).

Background Body composition from computed tomography (CT) scans is associated with cancer outcomes including surgical complications, chemotoxicity, and survival. Most studies manually segment CT scans, but Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) software automatically segments muscle and adipose tissues to speed analysis. Here, we externally evaluate ABACS in an independent dataset. Methods Among patients with non‐metastatic colorectal (n = 3102) and breast (n = 2888) cancer diagnosed from 2005 to 2013 at Kaiser Permanente, expert raters annotated tissue areas at the third lumbar vertebra (L3). To compare ABACS segmentation results to manual analysis, we quantified the proportion of pixel‐level image overlap using Jaccard scores and agreement between methods using intra‐class correlation coefficients for continuous tissue areas. We examined performance overall and among subgroups defined by patient and imaging characteristics. To compare the strength of the mortality associations obtained from ABACS's segmentations to manual analysis, we computed Cox proportional hazards ratios (HRs) and 95% confidence intervals (95% CI) by tertile of tissue area. Results Mean ± SD age was 63 ± 11 years for colorectal cancer patients and 56 ± 12 for breast cancer patients. There was strong agreement between manual and automatic segmentations overall and within subgroups of age, sex, body mass index, and cancer stage: average Jaccard scores and intra‐class correlation coefficients exceeded 90% for all tissues. ABACS underestimated muscle and visceral and subcutaneous adipose tissue areas by 1–2% versus manual analysis: mean differences were small at −2.35, −1.97 and −2.38 cm2, respectively. ABACS's performance was lowest for the <2% of patients who were underweight or had anatomic abnormalities. ABACS and manual analysis produced similar associations with mortality; comparing the lowest to highest tertile of skeletal muscle from ABACS versus manual analysis, the HRs were 1.23 (95% CI: 1.00–1.52) versus 1.38 (95% CI: 1.11–1.70) for colorectal cancer patients and 1.30 (95% CI: 1.01–1.66) versus 1.29 (95% CI: 1.00–1.65) for breast cancer patients. Conclusions In the first study to externally evaluate a commercially available software to assess body composition, automated segmentation of muscle and adipose tissues using ABACS was similar to manual analysis and associated with mortality after non‐metastatic cancer. Automated methods will accelerate body composition research and, eventually, facilitate integration of body composition measures into clinical care.

Objective: To prospectively examine the association between non-steroidal anti-inflammatory drugs (NSAIDs) use (including dose and dosage schedule) and the recurrence of colorectal adenomas among individuals who were diagnosed with an adenoma at entry into a clinical trial. Methods: For this analysis, participants who completed the full follow-up (n = 1905) for the Polyp Prevention Trial (PPT) were evaluated. Information on current use and dose of NSAIDs and other drugs was obtained at baseline and at each subsequent study visit over the duration of the trial. The study endpoint was the recurrence of colorectal adenomas in the 3 years between the 1-year trial colonoscopy (T1) and the end of the trial colonoscopy (T4). Results: There was a significant reduction in overall adenoma recurrence among NSAIDs users (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.63-0.95), with the greatest effect seen in advanced polyps (OR = 0.51; CI: 0.33-0.79). Among aspirin users, we observed a significant dose response for overall adenoma recurrence, with a 40% reduction in the OR association (OR = 0.56; 95% CI: 0.31-0.99) among those taking more than 325 mg per day. Conclusion: This prospective study provides further evidence that NSAIDs may play an important role in the chemoprevention of recurrent colorectal adenomas, even those with advanced features.

Objective: In this study we examine the combined effects of Western diet, age at diagnosis, and genetic susceptibility. Methods: We use data collected as part of an incident case-control study of colon cancer. Family history of colorectal cancer, N-acetyltransferase (NAT2), and gluathione-S-transferase (GSTM-1) are studied with Western diet and age at diagnosis. Results: A significant interaction between age at time of diagnosis, Western dietary pattern, and family history of colorectal cancer (p for interaction = 0.03) was detected. Those with a family history of colorectal cancer who ate a predominantly Western diet were at increased risk of colon cancer (OR 14.0, 95% CI 3.9-50.1 for ≤55 years; OR 7.7, 95% CI 2.0-29.1 for 56-66 years; OR 1.6, 95% CI 0.8-3.2 for ≥67 years) compared to those without a family history of colorectal cancer and low levels of a Western diet. Associations with the Western diet were stronger than individual components of the dietary pattern. Neither NAT2 nor GSTM-1 showed significant interaction with Western diet. Conclusion: The extent to which diet comprising a Western dietary pattern influences risk of colon cancer is dependent on age. This dietary pattern also appears to modulate the colon cancer risk associated with a family history of colon cancer.