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IMPORTANCE Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).OBJECTIVE To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.EXPOSURES Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use. MAIN OUTCOMES AND MEASURES Self-reported diagnosis of endometrial cancer.RESULTS Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Later age at menarche, parity (Ն1 live births), and hormonal contraceptive use (Ն1 year) were associated with a lower risk of endometrial cancer. No. (%) of Women Incidence Hazard Ratio (95% CI) With Available Data Diagnosed With Endometrial Cancer Incidence per 100 Person-Years Difference (95% CI) Age at menarche ≥13 Years 639 70 (11) 0.27 −0.04 (−0.15 to 0.05) 0.70 (0.44 to 1.11) <13 Years (reference) 454 57 (12.6) 0.31 Risk per year 0.85 (0.73 to 0.99) Parity ≥1 Live births 815 88 (10.8) 0.25 −0.18 (−0.32 to −0.04) 0.21 (0.10 to 0.42) Nulliparous (reference) 278 40 (14.4) 0.43 Hormonal contraceptive use ≥1 Year 803 70 (8.7) 0.22 −0.23 (−0.36 to −0.11) 0.39 (0.23 to 0.64) <1 Year (reference) 297 57 (19.2) 0.45 Risk per year 0.93 (0.89 to 0.97)There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use. CONCLUSIONS AND RELEVANCEFor women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer.

Background: Recent updates to physical activity guidelines highlight the importance of reducing sedentary time. However, at present, only general recommendations are possible (ie, “Sit less, move more”). There remains a need to investigate the strength, temporality, specificity, and dose–response nature of sedentary behavior associations with chronic disease, along with potential underlying mechanisms. Methods: Stemming from a recent research workshop organized by the Sedentary Behavior Council themed “Sedentary behaviour mechanisms—biological and behavioural pathways linking sitting to adverse health outcomes,” this paper (1) discusses existing challenges and scientific discussions within this advancing area of science, (2) highlights and discusses emerging areas of interest, and (3) points to potential future directions. Results: A brief knowledge update is provided, reflecting upon current and evolving thinking/discussions, and the rapid accumulation of new evidence linking sedentary behavior to chronic disease. Research “action points” are made at the end of each section—spanning from measurement systems and analytic methods, genetic epidemiology, causal mediation, and experimental studies to biological and behavioral determinants and mechanisms. Conclusion: A better understanding of whether and how sedentary behavior is causally related to chronic disease will allow for more meaningful conclusions in the future and assist in refining clinical and public health policies/recommendations.

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997–2012, except those identified as high-risk e.g. Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR=2.73; 95% CI: 1.30–5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR=4.16; 95% CI: 2.80–6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.

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This study aimed to assess vertical bone augmentation with simultaneous implant placement in rabbit tibiae using particulate mineralized bone/fibrin glue/mesenchymal stem cell. Bone marrow was aspirated from tibiae of five 10-week-old New Zealand White male rabbits. Right and left tibiae of each rabbit were prepared, and a 3-mm protruding implant from tibial bone was placed in each side. Particulate allogenic bone/fibrin glue/mesenchymal stem cell combination was placed around test implants and particulate bone graft/fibrin glue around controls. Two months postoperatively, the animals were euthanized, and sections were prepared for histological analysis. The mean amount of vertical bone length was higher in the experimental group than the control group (2.09 mm vs 1.03 mm; P < .05). New supracrestal trabecular bone formation was also significantly higher in the test group (28.5 ± 4.5% vs 4.3 ± 1.8%; P < .05). Mesenchymal stem cell/particulate allograft/fibrin glue appears to be a promising combination for vertical bone augmentation around simultaneously inserted implants in rabbit tibia.

Background People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol consumption and colorectal cancer. Results Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (standard deviation) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 grams/day and >28 grams/day were associated with increased colorectal cancer risk (HR, 1.50; 95%CI, 1.09–2.07 and 1.69; 95%CI, 1.07–2.65 respectively; P-trend=0.05), and colon cancer risk (HR, 1.78; 95%CI, 1.27–2.49 and 1.94; 95%CI, 1.19–3.18 respectively; P-trend=0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusion Our data suggests that alcohol consumption, particularly more than 28 grams/day of ethanol (~2 standard drinks of alcohol in the US), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk.