Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies

Genkinger, Jeanine M.; Kitahara, Cari M.; Bernstein, Leslie; González, Amy Berrington de; Brotzman, Michelle; Elena, Joanne W.; Giles, Graham G.; Hartge, Patricia; Singh, Pramil N.; Stolzenberg‐Solomon, Rachael Z.; Weiderpass, Elisabete; Adami, Hans Olov; Anderson, Kristin E.; Freeman, Laura E. Beane; Buring, Julie E.; Fraser, Gary E.; Fuchs, Charles S.; Gapstur, Susan M.; Gaziano, J. Michael; Helzlsouer, Kathy J.; Lacey, J.; Linet, Martha S.; Liu, J. J.; Park, Yikyung; Peters, Ulrike; Purdue, Mark P.; Robien, Kim; Schairer, Catherine; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Wolk, Alicja; Wolpin, Brian M.; Zeleniuch‐Jacquotte, Anne; Jacobs, Eric J.

doi:10.1093/annonc/mdv355

Cited by 134 publications

(94 citation statements)

References 59 publications

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“…15,16 Specifically, both central adiposity and an increased BMI, which is the most commonly used measure of obesity, are independently associated with PDAC-associated mortality. 17 One recent study also suggested that obesity is associated with worse survival following pancreaticoduodenectomy for PDAC. 15 One concern with utilizing BMI measurements as the sole measure of obesity is that it does not distinguish between visceral and subcutaneous fat.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Pancreatic Cancer–Associated Weight Loss and Nutritional Interventions

et al. 2017

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Objectives Pancreatic ductal adenocarcinoma (PDAC) is often accompanied by weight loss. We sought to characterize factors associated with weight loss and observed nutritional interventions, as well as define the effect of weight loss on survival. Methods Consecutive subjects diagnosed with PDAC (n = 123) were retrospectively evaluated. Univariate analysis was used to compare subjects with and without substantial (>5%) weight loss. Multivariate logistic regression was performed to identify factors associated with weight loss, and survival analyses were performed Kaplan-Meier curves and Cox survival models. Results Substantial weight loss at diagnosis was present in 71.5% of subjects, and was independently associated with higher baseline body mass index, longer symptom duration, and increased tumor size. Recommendations for nutrition consultation and pancreatic enzyme replacement therapy occurred in 27.6% and 36.9% of subjects, respectively. Weight loss (>5%) was not associated with worse survival on multivariate analysis (hazard ratio (HR) 1.32, 95% CI, 0.76–2.30), unless a higher threshold (>10%) was used (HR 1.77, 95% CI, 1.09–2.87). Conclusions Despite the high prevalence of weight loss at PDAC diagnosis, there are low observed rates of nutritional interventions. Weight loss based on current criteria for cancer cachexia is not associated with poor survival in PDAC.

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Section: Discussionmentioning

confidence: 99%

Predictors of Pancreatic Cancer–Associated Weight Loss and Nutritional Interventions

et al. 2017

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“…21,22 However, BMI is a limited measurement as it does not provide information on fat distribution, which is of importance as many of the complications associated with obesity have been shown to be closely related to abdominal obesity. 23,24 A recent pooled analysis of 20 prospective studies found that waist circumference is a risk factor for MM mortality and that BMI in early adulthood plays an important role later in life regarding MM mortality, particularly in women. 25 In addition, a recent cross-sectional study (n 5 72) found that patients recently diagnosed with MM had higher abdominal fat compared with patients with MGUS, indicating that this parameter might serve as a biomarker for progression from MGUS to MM.…”

Section: Introductionmentioning

confidence: 99%

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

et al. 2017

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Key Points• Obesity is not associated with MGUS or LC-MGUS.• High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.All multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases. Data from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (N 5 5764) were used. We performed serum protein electrophoresis and serum free light-chain assay on all subjects to identify MGUS and LC-MGUS cases. We included 11 different measures on current and previous obesity in our analysis. Logistic regression andCox proportional-hazard regression were used to analyze the associations. A total of 300 (5.2%) MGUS and 275 (4.8%) LC-MGUS cases were identified. During a median follow-up of 8 years, 18 had progressed to MM and 11 to other LP diseases. We found no association between the 11 obesity markers and MGUS or LC-MGUS (odds ratios 0.81 to 1.15 for all 11 variables in both conditions). Interestingly, we found that high midlife body mass index increased risk of progression to MM and other LP diseases (hazard ratio, 2.66; 95% confidence interval, 1.17-6.05). To conclude, obesity was not associated with MGUS. However, we found overweight/obesity to be a risk factor for progression from MGUS to MM and other LP diseases, suggesting that obesity plays a role in the transformation of MGUS to MM.

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“…Diabetes, obesity, and smoking are known risk factors for PDA (3–5). Large epidemiologic analyses have shown obesity is associated with higher risk of PDA in nonsmokers, however this association is weaker or absent in current smokers (4–6), suggesting obesity-related mechanisms may be of greater importance in the etiology of PDA in nonsmokers.…”

Section: Introductionmentioning

confidence: 99%

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

Nogueira

Newton

Pollak

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers. Methods We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate odds ratios (OR) and 95% confidence intervals (CI). Results Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per standard deviation OR=0.67, 95% CI 0.54, 0.84, p-interaction=0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR=0.43, 95% CI 0.23, 0.81), not associated in former smokers, and positively associated in smokers (OR=1.23, 95% CI 1.04, 1.45, p-interaction=0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers. Conclusion Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance explain associations in non-smokers. Impact Future studies of these biomarkers and PDA should examine results by smoking status.

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Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies

Abstract: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Cited by 134 publications

References 59 publications

Predictors of Pancreatic Cancer–Associated Weight Loss and Nutritional Interventions

Predictors of Pancreatic Cancer–Associated Weight Loss and Nutritional Interventions

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

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