Publications by authors named "Bette J Caan"

238 Publications

Abdominal adipose tissue radiodensity is associated with survival after colorectal cancer.

Am J Clin Nutr 2021 Sep 12. Epub 2021 Sep 12.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: Adipose tissue radiodensity may have prognostic importance for colorectal cancer (CRC) survival. Lower radiodensity is indicative of larger adipocytes, while higher radiodensity may represent adipocyte atrophy, inflammation, or edema.

Objectives: We investigated associations of adipose tissue radiodensity and longitudinal changes in adipose tissue radiodensity with mortality among patients with nonmetastatic CRC.

Methods: In 3023 patients with stage I-III CRC, radiodensities of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from diagnostic computed tomography (CT) images. There were 1775 patients with follow-up images available. Cox proportional hazards models and restricted cubic splines were used to examine associations of at-diagnosis values and of longitudinal changes in VAT and SAT radiodensities with risks of death after adjusting for potential confounders, including body size and comorbidities.

Results: VAT and SAT radiodensities were linearly associated with all-cause mortality: the HRs for death per SD increase were 1.21 (95% CI, 1.11-1.32) for VAT radiodensity and 1.18 (95% CI, 1.11-1.26) for SAT radiodensity. Changes in adipose tissue radiodensity had curvilinear associations with risks of death. The HR for an increase in VAT radiodensity of at least 1 SD was 1.53 (95% CI, 1.23-1.90), while the HR for a decrease of at least 1 SD was nonsignificant at 1.11 (95% CI, 0.84-1.47) compared with maintaining radiodensity within 1 SD of baseline. Similarly, increases (HR, 1.88; 95% CI, 1.48-2.40) but not decreases (HR, 1.20; 95% CI, 0.94-1.54) in SAT radiodensity significantly increased the risk of death compared with no change in radiodensity.

Conclusions: In patients with nonmetastatic CRC, adipose tissue radiodensity is a novel risk factor for total mortality that is independent of BMI and changes in body weight.
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http://dx.doi.org/10.1093/ajcn/nqab285DOI Listing
September 2021

Individual- and neighborhood-level socioeconomic status and risk of aggressive breast cancer subtypes in a pooled cohort of women from Kaiser Permanente Northern California.

Cancer 2021 Aug 20. Epub 2021 Aug 20.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures.

Methods: This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES.

Results: In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [OR ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (OR , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype.

Conclusions: nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA.
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http://dx.doi.org/10.1002/cncr.33861DOI Listing
August 2021

Sarcopenia in the Older Adult With Cancer.

J Clin Oncol 2021 Jul 27;39(19):2068-2078. Epub 2021 May 27.

Division of Research, Kaiser Permanente, Oakland, CA.

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http://dx.doi.org/10.1200/JCO.21.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260902PMC
July 2021

The Role of Home-Based Exercise in Maintaining Skeletal Muscle During Preoperative Pancreatic Cancer Treatment.

Integr Cancer Ther 2021 Jan-Dec;20:1534735420986615

MD Anderson Cancer Center, Houston, TX, USA.

Loss of skeletal muscle and inferior muscle quality are associated with poor prognosis in patients undergoing preoperative treatment for pancreatic cancer, so maintaining skeletal muscle health before surgery may help accelerate patients' functional recovery and improve their quality of life following surgery. While exercise helps maintain or increase skeletal muscle in individuals undergoing cancer treatment, its efficacy during pancreatic cancer treatment is unclear. Accordingly, in this study we compared changes in skeletal muscle quantity (skeletal muscle index [SMI]) and quality (skeletal muscle density [SMD]) during preoperative pancreatic cancer treatment in participants in a home-based exercise program (EP) and a historical cohort of patients who received the usual care (UC) with no formal exercise programming. Recommendations for the EP cohort included both aerobic and resistance exercise. We assessed changes in SMI and SMD using computed tomography scans administered at treatment planning (T0, prior to EP enrollment) and preoperative restaging (T1) for 33 EP and 64 UC patients and compared changes between groups. The UC patients had statistically significant SMI decreases from T0 to T1 (-1.4 ± 3.8 cm/m;  = .005), while the EP patients did not (0.2 ± 3.2 cm/m;  = .7). The SMI loss was significantly worse for the UC than for the EP patients ( = .03). Neither group demonstrated statistically significant changes in SMD from T0 to T1, nor did the groups differ in the amount of change in SMD. An adjusted linear regression model demonstrated that EP participation was significantly associated with better SMI maintenance ( = .02). These results suggest that participation in a home-based EP during preoperative treatment may help improve skeletal muscle health and clinical and quality of life outcomes for pancreatic cancer survivors.
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http://dx.doi.org/10.1177/1534735420986615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056559PMC
April 2021

Weight stability masks changes in body composition in colorectal cancer: a retrospective cohort study.

Am J Clin Nutr 2021 06;113(6):1482-1489

Dana-Farber Cancer Institute, Boston, MA, USA.

Background: There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion.

Objectives: We aimed to determine whether body weight stability is associated with skeletal muscle depletion and whether skeletal muscle depletion is prognostic of death independently of change in body weight.

Methods: This retrospective cohort included 1921 patients with stage I-III colorectal cancer. Computed tomography (CT)-based skeletal muscle characteristics and body weight were measured at diagnosis and after a mean 15.0-mo follow-up. Body weight stability was defined as weight change less than ±5% during follow-up. Sarcopenia and myosteatosis were defined using established thresholds for patients with cancer. Multivariable-adjusted logistic and flexible parametric proportional hazards survival models were used to quantify statistical associations.

Results: At follow-up, 1026 (53.3%) patients were weight stable. Among patients with weight stability, incident sarcopenia and myosteatosis occurred in 8.5% (95% CI: 6.3%, 10.6%) and 13.5% (95% CI: 11.1%, 15.9%), respectively. Men were more likely to be weight stable than were women (56.7% compared with 49.9%; P = 0.04). Weight-stable men were less likely to develop incident sarcopenia (5.4% compared with 15.4%; P = 0.003) and myosteatosis (9.3% compared with 20.8%; P = 0.001) than weight-stable women. Among all patients, the development of incident sarcopenia (HR: 1.40; 95% CI: 1.02, 1.91) and of myosteatosis (HR: 1.41; 95% CI: 1.05, 1.90) were associated with a higher risk of death, independently of change in body weight. Patient sex did not modify the relation between skeletal muscle depletion and death.

Conclusions: Body weight stability masks clinically meaningful skeletal muscle depletion. Body composition quantified using clinically acquired CT images may provide a vital sign to identify patients at increased risk of death. These data may inform the design of future cachexia trials.
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http://dx.doi.org/10.1093/ajcn/nqaa440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168363PMC
June 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Gut 2021 Jul 25;70(7):1325-1334. Epub 2021 Feb 25.

Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

Results: We identified 13 loci that reached genome-wide significance (p<5×10) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223655PMC
July 2021

Alignment of Dietary Patterns With the Dietary Guidelines for Americans 2015-2020 and Risk of All-Cause and Cause-Specific Mortality in the Women's Health Initiative Observational Study.

Am J Epidemiol 2021 05;190(5):886-892

Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women's Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015-2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.
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http://dx.doi.org/10.1093/aje/kwaa268DOI Listing
May 2021

Recruitment strategies and design considerations in a trial of resistance training to prevent dose-limiting toxicities in colon cancer patients undergoing chemotherapy.

Contemp Clin Trials 2021 02 7;101:106242. Epub 2020 Dec 7.

Penn State Cancer Institute, The Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA. Electronic address:

Low muscle is associated with an increased risk of chemotherapy-related dose limiting toxicities (DLT) in cancer patients. Resistance training (RT) improves muscle mass; however, the effects of RT on preventing DLTs and dose reductions in colon cancer patients has not been investigated. FOcus on Reducing dose-limiting toxicities in Colon cancer with resistance Exercise (FORCE) is a multicenter, randomized clinical trial examining the effects of RT on relative dose intensity (RDI; primary outcome) and moderate and severe chemotoxicities (primary outcome) in non-metastatic colon cancer patients receiving adjuvant chemotherapy. Patients (N = 180) will be recruited from Kaiser Permanente Northern California, Dana-Farber Cancer Institute, and Penn State Cancer Institute. This paper describes recruitment strategies and design considerations. Patients will be randomized in equal numbers to RT intervention or control. Patients have baseline and post completion of chemotherapy visits where information on anthropometry, physical function, body composition, quality of life, physical activity and dietary behaviors, and inflammatory blood markers will be collected. Patient-reported outcomes of chemotherapy side effects will be collected around the time of chemotherapy throughout the duration of the trial. Intervention participants will be prescribed a progressive RT program consisting of 4-6 visits with a certified exercise trainer, delivered either in-person or remotely by video conference, and will be asked to engage twice weekly in-home training sessions. Control patients at the end of the study receive a consult with a FORCE exercise trainer, an online exercise RT training program and a set of resistance bands. Results of this trial will provide information on the benefit of resistance exercise as a treatment to increase RDI.
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http://dx.doi.org/10.1016/j.cct.2020.106242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954871PMC
February 2021

Authors Response.

J Acad Nutr Diet 2021 02 13;121(2):210-212. Epub 2020 Nov 13.

Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.

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http://dx.doi.org/10.1016/j.jand.2020.10.015DOI Listing
February 2021

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

Cancer 2021 02 5;127(4):598-608. Epub 2020 Nov 5.

Department of Oncology, Barbara Ann Karmanos Cancer Institute at Wayne State University, Detroit, Michigan.

Background: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer.

Methods: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival.

Results: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42).

Conclusions: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation.

Lay Summary: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.
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http://dx.doi.org/10.1002/cncr.33295DOI Listing
February 2021

Association of Prediagnostic Frailty, Change in Frailty Status, and Mortality After Cancer Diagnosis in the Women's Health Initiative.

JAMA Netw Open 2020 09 1;3(9):e2016747. Epub 2020 Sep 1.

Division of Research, Kaiser Permanente Northern California, Oakland.

Importance: Understanding changes in frailty in relation to cancer diagnosis can inform optimal selection of cancer treatments and survivorship care.

Objective: To investigate associations of prediagnostic frailty and change in frailty status with mortality after a cancer diagnosis.

Design, Setting, And Participants: This multicenter, prospective cohort study included 7257 community-dwelling, postmenopausal women in the United States who had frailty assessed at the Women's Health Initiative (WHI) enrollment (1993-1998) and the 3-year visit who were subsequently diagnosed as having invasive cancer. The data were analyzed from January 7, 2019, to June, 8, 2020.

Exposure: Frailty scores were defined from validated questionnaire items conceptually aligned with the Fried frailty phenotype, including at least 3 of the following characteristics: self-reported unintentional weight loss, exhaustion, low physical activity, and muscle weakness or impaired walking. Physical function components of the frailty score were updated a median of 10 (range, 1-18) times.

Main Outcomes And Measures: Using multivariable-adjusted Cox proportional hazards models, this study examined associations of prediagnostic frailty (at the 3-year visit, before cancer diagnosis) and prediagnostic changes in frailty (from enrollment to the 3-year visit) with mortality. Women were followed up beginning from cancer diagnosis for mortality outcomes through March 2018. In linear mixed-effects models with frailty scores as a function of time since cancer diagnosis, this study evaluated whether the time slope, ie, the rate of change in frailty score, increased after cancer diagnosis.

Results: This study included 7257 women in the WHI cohort who completed frailty assessments at enrollment and the 3-year WHI visit before cancer diagnosis and subsequently developed cancer. Cancer cases included 2644 breast cancers (36%), 822 lung cancers (11%), 691 colorectal cancers (10%), 445 endometrial cancers (6%), and 286 ovarian cancers (4%). At the 3-year visit, prior to cancer diagnosis, the mean (SD) age was 63 (7) years, and 1161 of 7257 (16%) of participating women met criteria for frailty; 2129 of 7257 (29%) were prefrail, and 3967 of 7257 (55%) were nonfrail. Over a median follow-up of 5.8 years after cancer diagnosis (range, 1 day to 19.9 years), 3056 women died. After multivariable adjustment, women who were frail (vs nonfrail) before cancer diagnosis had an increased risk of mortality after cancer diagnosis (hazard ratio [HR], 1.40; 95% CI, 1.26-1.55; P for trend <.001). Sustained frailty (21% [1537 of 7257] of women) or worsening frailty (22% [1578 of 7257]) vs being consistently nonfrail (45% [3266 of 7257]) before cancer diagnosis increased the risk of mortality after cancer diagnosis (HR, 1.25; 95% CI, 1.14-1.38 and 1.22; 95% CI, 1.11-1.34, respectively; P for trend <.001). In linear mixed-effects models, the rate of increase in physical frailty over time was statistically significantly higher after cancer diagnosis.

Conclusions And Relevance: Sustained and worsening frailty before cancer diagnosis was associated with an increased risk of mortality after cancer diagnosis in postmenopausal women. Furthermore, the rate of decline in physical function accelerated after cancer diagnosis. Frailty assessment could provide valuable information and perhaps prompt interventions to reduce and preempt worsening of physical frailty after cancer diagnosis.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.16747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490646PMC
September 2020

Deep learning method for localization and segmentation of abdominal CT.

Comput Med Imaging Graph 2020 10 14;85:101776. Epub 2020 Aug 14.

School of Engineering Science, Simon Fraser University, Canada.

Computed Tomography (CT) imaging is widely used for studying body composition, i.e., the proportion of muscle and fat tissues with applications in areas such as nutrition or chemotherapy dose design. In particular, axial CT slices from the 3rd lumbar (L3) vertebral location are commonly used for body composition analysis. However, selection of the third lumbar vertebral slice and the segmentation of muscle/fat in the slice is a tedious operation if performed manually. The objective of this study is to automatically find the middle axial slice at L3 level from a full or partial body CT scan volume and segment the skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) on that slice. The proposed algorithm includes an L3 axial slice localization network followed by a muscle-fat segmentation network. The localization network is a fully convolutional classifier trained on more than 12,000 images. The segmentation network is a convolutional neural network with an encoder-decoder architecture. Three datasets with CT images taken for patients with different types of cancers are used for training and validation of the networks. The mean slice error of 0.87±2.54 was achieved for L3 slice localization on 1748 CT scan volumes. The performance of five class tissue segmentation network evaluated on two datasets with 1327 and 1202 test samples. The mean Jaccard score of 97% was achieved for SM and VAT tissue segmentation on 1327 images. The mean Jaccard scores of 98% and 83% are corresponding to SAT and IMAT tissue segmentation on the same dataset. The localization and segmentation network performance indicates the potential for fully automated body composition analysis with high accuracy.
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http://dx.doi.org/10.1016/j.compmedimag.2020.101776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803471PMC
October 2020

Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery.

JAMA Surg 2020 10;155(10):942-949

Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.

Importance: Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification.

Objective: To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer.

Design, Setting, And Participants: This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020.

Exposures: Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images.

Main Outcomes And Measures: Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality.

Results: The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04).

Conclusions And Relevance: Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.
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http://dx.doi.org/10.1001/jamasurg.2020.2497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424546PMC
October 2020

Dietary Intakes of Women's Health Initiative Long Life Study Participants Falls Short of the Dietary Reference Intakes.

J Acad Nutr Diet 2020 09 14;120(9):1530-1537. Epub 2020 Jul 14.

Background: Understanding how nutrient intake in older women compares with recommendations is important. The Academy of Nutrition and Dietetics position statement summarizes the nutrient needs of older adults (aged ≥60 years) based on a systematic review.

Objective: The objective of this study was to compare nutrient intake of Women's Health Initiative Long Life Study participants to the Dietary Reference Intakes for nutrients reviewed in the Academy of Nutrition and Dietetics position statement.

Design: The study is a cross-sectional analysis.

Participants/setting: Participants (n=7,875) were mailed the General Nutrition Assessment Food Frequency Questionnaire during 2012-2013, of whom 77% (n=6,095) completed it, and 5,732 were included in the analytic sample after exclusion for implausible energy intakes.

Main Outcome Measures: Mean intake of energy and protein, calcium, fiber, folate, potassium, sodium, vitamins B-12, D, E, and K were described overall and compared with recommendations.

Statistical Analyses Performed: Demographic and lifestyle characteristics were summarized using descriptive statistics. The proportion of participants meeting recommendations was computed.

Results: Mean age of completers was 79±7 years and 53.5% were non-Hispanic white, 30% were non-Hispanic black, and 16.5% were Hispanic/Latina. Only one-third of women consumed ≥21 g/day fiber, whereas fewer met the Recommended Dietary Allowance for calcium (18.6%), vitamin E (16.9%), and vitamin D (1.7%). Just more than half (56%) of participants met the Recommended Dietary Allowance for protein of 0.8 g/kg body weight/day, and just less than half (47.0%) met potassium guidelines.

Conclusions: These findings suggest older women within the Women's Health Initiative were generally not achieving recommended intake for several key nutrients highlighted by the Academy of Nutrition and Dietetics position statement. These findings underscore the need to identify effective approaches for improving the nutrient density of dietary intake in older women.
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http://dx.doi.org/10.1016/j.jand.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566285PMC
September 2020

Myocardial infarction accelerates breast cancer via innate immune reprogramming.

Nat Med 2020 09 13;26(9):1452-1458. Epub 2020 Jul 13.

NYU Cardiovascular Research Center, Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA.

Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity or surgery, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6C monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6C monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.
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http://dx.doi.org/10.1038/s41591-020-0964-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789095PMC
September 2020

American Cancer Society guideline for diet and physical activity for cancer prevention.

CA Cancer J Clin 2020 07 9;70(4):245-271. Epub 2020 Jun 9.

Cancer Control, American Cancer Society, Atlanta, Georgia.

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
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http://dx.doi.org/10.3322/caac.21591DOI Listing
July 2020

Evaluation of automated computed tomography segmentation to assess body composition and mortality associations in cancer patients.

J Cachexia Sarcopenia Muscle 2020 10 20;11(5):1258-1269. Epub 2020 Apr 20.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

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 cm , 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.
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http://dx.doi.org/10.1002/jcsm.12573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567141PMC
October 2020

Prediagnosis social support, social integration, living status, and colorectal cancer mortality in postmenopausal women from the women's health initiative.

Cancer 2020 04 23;126(8):1766-1775. Epub 2020 Jan 23.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: We evaluated associations between perceived social support, social integration, living alone, and colorectal cancer (CRC) outcomes in postmenopausal women.

Methods: The study included 1431 women from the Women's Health Initiative who were diagnosed from 1993 through 2017 with stage I through IV CRC and who responded to the Medical Outcomes Study Social Support survey before their CRC diagnosis. We used proportional hazards regression to evaluate associations of social support (tertiles) and types of support, assessed up to 6 years before diagnosis, with overall and CRC-specific mortality. We also assessed associations of social integration and living alone with outcomes also in a subset of 1141 women who had information available on social ties (marital/partner status, community and religious participation) and living situation.

Results: In multivariable analyses, women with low (hazard ratio [HR], 1.52; 95% CI, 1.23-1.88) and moderate (HR, 1.21; 95% CI, 0.98-1.50) perceived social support had significantly higher overall mortality than those with high support (P [continuous] < .001). Similarly, women with low (HR, 1.42; 95% CI, 1.07-1.88) and moderate (HR, 1.28; 95% CI, 0.96-1.70) perceived social support had higher CRC mortality than those with high social support (P [continuous] = .007). Emotional, informational, and tangible support and positive interaction were all significantly associated with outcomes, whereas affection was not. In main-effects analyses, the level of social integration was related to overall mortality (P for trend = .02), but not CRC mortality (P for trend = .25), and living alone was not associated with mortality outcomes. However, both the level of social integration and living alone were related to outcomes in patients with rectal cancer.

Conclusions: Women with low perceived social support before diagnosis have higher overall and CRC-specific mortality.
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http://dx.doi.org/10.1002/cncr.32710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297047PMC
April 2020

Sustained Weight Loss and Risk of Breast Cancer in Women 50 Years and Older: A Pooled Analysis of Prospective Data.

J Natl Cancer Inst 2020 09;112(9):929-937

Department of Epidemiology.

Background: Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk.

Methods: Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up.

Results: Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5-<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight.

Conclusions: These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.
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http://dx.doi.org/10.1093/jnci/djz226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492760PMC
September 2020

Body Composition, Adherence to Anthracycline and Taxane-Based Chemotherapy, and Survival After Nonmetastatic Breast Cancer.

JAMA Oncol 2020 02;6(2):264-270

Division of Research, Kaiser Permanente Northern California, Oakland.

Importance: Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence.

Objectives: To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality.

Design, Setting, And Participants: An observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019.

Exposures: Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis.

Main Outcomes And Measures: The primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method.

Results: The mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55).

Conclusions And Relevance: Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.
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http://dx.doi.org/10.1001/jamaoncol.2019.4668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902178PMC
February 2020

Guideline-concordant endometrial cancer treatment and survival in the Women's Health Initiative Life and Longevity After Cancer study.

Int J Cancer 2020 07 31;147(2):404-412. Epub 2019 Oct 31.

Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH.

In the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) cohort, we examined predictors of guideline-concordant treatment among endometrial cancer (EC) survivors and associations between receipt of guideline-concordant treatment and survival. Receipt of guideline-concordant EC treatment was defined according to year-specific National Comprehensive Cancer Network (NCCN) guidelines. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of guideline-concordant treatment receipt. We estimated multivariable-adjusted hazard ratios (HRs) and 95% CIs for relationships between guideline-concordant treatment and overall survival using Cox proportional hazards regression. We included 629 women with EC, of whom 83.6% (n = 526) received guideline-concordant treatment. Receipt of guideline-concordant treatment was less common among women with nonendometrioid histology (OR = 0.24, 95% CI = 0.13-0.45) but was more common among women living in the Midwest (OR = 2.09, 95% CI = 1.06-4.12) or West (OR = 3.02, 95% CI = 1.49-6.13) compared to the Northeast. In Cox regression models adjusted for age, histology and stage, receipt of guideline-concordant EC treatment was borderline associated with improved overall survival (HR = 0.80, 95% CI = 0.60-1.01) in the overall population. Guideline-concordant treatment was also linked with better overall survival among women with low-grade uterine-confined endometrioid EC or widely metastatic endometrioid EC. Guideline-concordant treatment varies by some patient characteristics and those women in receipt of guideline-concordant care had borderline improved survival. Studies evaluating regional differences in treatment along with randomized clinical trials to determine appropriate treatment regimens for women with aggressive tumor characteristics are warranted.
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http://dx.doi.org/10.1002/ijc.32740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160046PMC
July 2020

Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis.

Int J Gynecol Cancer 2019 11 26;29(9):1361-1371. Epub 2019 Aug 26.

Division of Epidemiology, The Ohio State University College of Public Health, Columbus, OH, USA

Purpose: Weight cycling, defined as intentional weight loss followed by unintentional weight regain, may attenuate the benefit of intentional weight loss on endometrial cancer risk. We summarized the literature on intentional weight loss, weight cycling after intentional weight loss, bariatric surgery, and endometrial cancer risk.

Methods: A systematic search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases published between January 2000 and November 2018. We followed Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) guidelines. We qualitatively summarized studies related to intentional weight loss and weight cycling due to the inconsistent definition, and quantitatively summarized studies when bariatric surgery was the mechanism of intentional weight loss.

Results: A total of 127 full-text articles were reviewed, and 13 were included (bariatric surgery n=7, self-reported intentional weight loss n=2, self-reported weight cycling n=4). Qualitative synthesis suggested that, compared with stable weight, self-reported intentional weight loss was associated with lower endometrial cancer risk (RR range 0.61-0.96), whereas self-reported weight cycling was associated with higher endometrial cancer risk (OR range 1.07-2.33). The meta-analysis yielded a 59% lower risk of endometrial cancer following bariatric surgery (OR 0.41, 95% CI 0.22 to 0.74).

Conclusions: Our findings support the notion that intentional weight loss and maintenance of a stable, healthy weight can lower endometrial cancer risk. Strategies to improve awareness and maintenance of weight loss among women with obesity are needed to reduce endometrial cancer risk.
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http://dx.doi.org/10.1136/ijgc-2019-000728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832748PMC
November 2019

Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors.

J Clin Oncol 2019 10 1;37(28):2528-2536. Epub 2019 Aug 1.

Kaiser Permanente Northern California, Oakland, CA.

Purpose: Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer.

Methods: Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors.

Results: Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]).

Conclusion: Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.
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http://dx.doi.org/10.1200/JCO.19.00286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001794PMC
October 2019

The Association of Abdominal Adiposity With Mortality in Patients With Stage I-III Colorectal Cancer.

J Natl Cancer Inst 2020 04;112(4):377-383

Dana-Farber Cancer Institute, Boston, MA.

Background: The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex.

Methods: This cohort included 3262 stage I-III colorectal cancer patients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values.

Results: Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P = .02); risk was flat to a threshold (∼260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P < .001); risk was higher at extreme (<50 cm2) but lower at intermediate values (>50 to ≤560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (Pinteraction = .049) and subcutaneous adipose tissue (Pinteraction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P = .003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P = .008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P = .01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P < .001).

Conclusions: Visceral and subcutaneous adipose tissue were prognostic of mortality in patients with colorectal cancer; the shape of these associations were often nonlinear and varied by patient sex. These results offer insight into the potential biological mechanisms that link obesity with clinical outcomes in patients with cancer, suggesting that the dysregulated deposition of excess adiposity is prognostic of mortality.
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http://dx.doi.org/10.1093/jnci/djz150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156926PMC
April 2020

Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal Women.

JAMA Netw Open 2019 07 3;2(7):e197337. Epub 2019 Jul 3.

Department of Epidemiology, College of Public Health, University of Iowa, Iowa City.

Importance: Current public health guidelines for obesity prevention and control focus on promoting a normal body mass index (BMI), rarely addressing central obesity, which is reflected by high waist circumference (WC) and common in the general population. Studies of the association of normal-weight central obesity with long-term health outcomes are sparse.

Objective: To examine associations of normal-weight central obesity with all-cause and cause-specific mortality in postmenopausal women in the United States.

Design, Setting, And Participants: A nationwide prospective cohort study of 156 624 postmenopausal women enrolled in the Women's Health Initiative at 40 clinical centers in the United States between 1993 and 1998. These women were observed through February 2017. Data analysis was performed from September 15, 2017, to March 13, 2019.

Exposures: Different combinations of BMI (calculated as weight in kilograms divided by height in meters squared; normal weight: BMI, 18.5-24.9; overweight: BMI, 25.0-29.9; and obesity: BMI, ≥30) and WC (normal: WC, ≤88 cm and high: WC, >88 cm).

Main Outcomes And Measures: Mortality from all causes, cardiovascular disease, and cancer.

Results: Of the 156 624 women (mean [SD] age, 63.2 [7.2] years), during 2 811 187 person-years of follow-up, 43 838 deaths occurred, including 12 965 deaths from cardiovascular disease (29.6%) and 11 828 deaths from cancer (27.0%). Compared with women with normal weight and no central obesity and adjusted for demographic characteristics, socioeconomic status, lifestyle factors, and hormone use, the hazard ratio for all-cause mortality was 1.31 (95% CI, 1.20-1.42) among women with normal weight and central obesity, 0.91 (95% CI, 0.89-0.94) among women with overweight and no central obesity, 1.16 (95% CI, 1.13-1.20) for women with overweight and central obesity, 0.93 (95% CI, 0.89-0.94) for women with obesity and no central obesity, and 1.30 (95% CI, 1.27-1.34) for women with obesity and central obesity. Compared with normal weight without central obesity, normal-weight central obesity was associated with higher risk of cardiovascular disease mortality (hazard ratio, 1.25; 95% CI, 1.05-1.46) and cancer mortality (hazard ratio, 1.20; 95% CI, 1.01-1.43).

Conclusions And Relevance: Normal-weight central obesity in women was associated with excess risk of mortality, similar to that of women with BMI-defined obesity with central obesity. These findings underscore the need for future public health guidelines to include the prevention and control of central obesity, even in individuals with normal BMI.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.7337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659146PMC
July 2019

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility.

Int J Cancer 2020 01 4;146(2):363-372. Epub 2019 Jul 4.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.
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http://dx.doi.org/10.1002/ijc.32516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301215PMC
January 2020

Muscle segmentation in axial computed tomography (CT) images at the lumbar (L3) and thoracic (T4) levels for body composition analysis.

Comput Med Imaging Graph 2019 07 9;75:47-55. Epub 2019 May 9.

School of Engineering Science, Simon Fraser University, Canada.

In diseases such as cancer, patients suffer from degenerative loss of skeletal muscle (cachexia). Muscle wasting and loss of muscle function/performance (sarcopenia) can also occur during advanced aging. Assessing skeletal muscle mass in sarcopenia and cachexia is therefore of clinical interest for risk stratification. In comparison with fat, body fluids and bone, quantifying the skeletal muscle mass is more challenging. Computed tomography (CT) is one of the gold standard techniques for cancer diagnostics and analysis of progression, and therefore a valuable source of imaging for in vivo quantification of skeletal muscle mass. In this paper, we design a novel deep neural network-based algorithm for the automated segmentation of skeletal muscle in axial CT images at the third lumbar (L3) and the fourth thoracic (T4) levels. A two-branch network with two training steps is investigated. The network's performance is evaluated for three trained models on separate datasets. These datasets were generated by different CT devices and data acquisition settings. To ensure the model's robustness, each trained model was tested on all three available test sets. Errors and the effect of labeling protocol in these cases were analyzed and reported. The best performance of the proposed algorithm was achieved on 1327 L3 test samples with an overlap Jaccard score of 98% and sensitivity and specificity greater than 99%.
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http://dx.doi.org/10.1016/j.compmedimag.2019.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620151PMC
July 2019

Body Composition and Cardiovascular Events in Patients With Colorectal Cancer: A Population-Based Retrospective Cohort Study.

JAMA Oncol 2019 Jul;5(7):967-972

Dana-Farber Cancer Institute, Boston, Massachusetts.

Importance: Patients with colorectal cancer (CRC) are up to 4-fold more likely than individuals without a history of cancer to develop cardiovascular disease. Clinical care guidelines recommend that physicians counsel patients with CRC regarding the association between obesity (defined using body mass index [BMI] calculated as weight in kilograms divided by height in meters squared) and cardiovascular disease risk; however, this recommendation is based on expert opinion.

Objective: To determine which measures of body composition are associated with major adverse cardiovascular events (MACEs) in patients with CRC.

Design, Setting, And Participants: Population-based retrospective cohort study of 2839 patients with stage I to III CRC diagnosed between January 2006 and December 2011 at an integrated health care system in North America.

Exposures: The primary exposures were BMI and computed tomography-derived body composition measurements (eg, adipose tissue compartments and muscle characteristics) obtained at the diagnosis of CRC.

Main Outcomes And Measures: The primary outcome was time to the first occurrence of MACE after diagnosis of CRC, including myocardial infarction, stroke, and cardiovascular death.

Results: In this population-based cohort study of 2839 participants with CRC (1384 men and 1455 women), the average age (SD) was 61.9 (11.5) years (range, 19-80 years). A substantial number of patients were former (1127; 40%) or current smokers (340; 12%), with hypertension (1150; 55%), hyperlipidemia (1389; 49%), and type 2 diabetes (573; 20%). The cumulative incidence of MACE 10 years after diagnosis of CRC was 19.1%. Body mass index was positively correlated with some computed tomography-derived measures of body composition. However, BMI was not associated with MACE; contrasting BMI categories of greater than or equal to 35 vs 18.5 to 24.9, the hazard ratio (HR) was 1.23 (95% CI, 0.85-1.77; P = .50 for trend). Visceral adipose tissue area was associated with MACE; contrasting the highest vs lowest quintile, the HR was 1.54 (95% CI, 1.02-2.31; P = .04 for trend). Subcutaneous adipose tissue area was not associated with MACE; contrasting the highest vs lowest quintile, the HR was 1.15 (95% CI, 0.78-1.69; P = .65 for trend). Muscle mass was not associated with MACE; contrasting the highest vs lowest quintile, the HR was 0.96 (95% CI, 0.57-1.61; P = .92 for trend). Muscle radiodensity was associated with MACE; contrasting the highest (ie, less lipid stored in the muscle) vs lowest quintile, the HR was 0.67 (95% CI, 0.44-1.03; P = .02 for trend).

Conclusions And Relevance: Visceral adiposity and muscle radiodensity appear to be risk factors for MACE. Body mass index may have limited use for determining cardiovascular risk in this patient population.
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http://dx.doi.org/10.1001/jamaoncol.2019.0695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537811PMC
July 2019

Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.

Int J Cancer 2020 02 7;146(3):861-873. Epub 2019 Jun 7.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
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http://dx.doi.org/10.1002/ijc.32377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819207PMC
February 2020
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