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Obesity and components of energy imbalance, i.e., excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included: 1) mechanisms associated with obesity and energy balance that influence cancer progression; 2) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; 3) associations between obesity and cancer risk, recurrence, and mortality; 4) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and 5) future directions.

Background: Colorectal cancer, the third most common cancer in the United States, has a natural history that usually encompasses several decades. Dietary components have been implicated in the etiology of colorectal cancer, perhaps through their effect on inflammation.Methods: We examined the ability of the dietary inflammatory index (DII) to predict colorectal cancer in the Iowa Women's Health Study. The DII was computed based on dietary intake assessed by a 121-item food frequency questionnaire in this cohort of 34,703 women, ages 55 to 69 years, free of any self-reported prior malignancy at enrollment in 1986. Incident colorectal cancer cases were identified through linkage with the State Health Registry of Iowa (a Surveillance, Epidemiology, and End Results program member). Cox proportional hazards regression was used to estimate HRs. Through the end of 2010, 1,636 incident colorectal cancers were identified, including 1,329 colon and 325 rectal cancers.Results: Multivariable analysis, adjusting for body mass index, smoking status, pack-years of smoking, hormone replacement therapy, education, diabetes, and total energy intake, revealed positive associations between higher DII and colorectal cancer risk [HR for DII continuous : 1.07 per unit increase in DII (corresponding to 0.5 SD unit increase); 95% confidence interval (CI), 1.01-1.13; HR for DII quintiles : Q5 vs. Q1 ¼ 1.20; 95% CI, 1.01-1.43]. HRs for DII were similar for colon cancer and rectal cancer, though not statistically significant for rectal cancer.Conclusions: These results indicate that a proinflammatory diet, as indicated by higher DII scores, was associated with higher risk of developing colorectal cancer.Impact: Proinflammatory diets are associated with increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(11); 2383-92. Ó2014 AACR.

Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression.

APOE epsilon4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among epsilon2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.

Obesity exerts adverse effects on breast cancer survival, but the means have not been fully elucidated. We evaluated obesity as a contributor to breast cancer survival according to tumor molecular subtypes in a population-based case–cohort study using data from the Surveillance Epidemiology and End Results (SEER) program. We determined whether obese women were more likely to be diagnosed with poor prognosis tumor characteristics and quantified the contribution of obesity to survival. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated via Cox multivariate models. The effect of obesity on survival was evaluated among 859 incident breast cancers (subcohort; 15% random sample; median survival 7.8 years) and 697 deaths from breast cancer (cases; 100% sample). Obese women had a 1.7- and 1.8-fold increased risk of stage III/IV disease and grade 3/4 tumors, respectively. Obese women with Luminal A- and Luminal B-like breast cancer were 1.8 (95% CI 1.3–2.5) and 2.2 (95% CI 0.9–5.0) times more likely to die from their cancer compared to normal weight women. In mediation analyses, the proportion of excess mortality attributable to tumor characteristics was 36.1% overall and 41% and 38% for Luminal A- and Luminal B-like disease, respectively. Obesity was not associated with breast cancer-specific mortality among women who had Her2-overexpressing or triple-negative tumors. Obesity may influence hormone-positive breast cancer-specific mortality in part through fostering poor prognosis tumors. When tumor biology is considered as part of the causal pathway, the public health impact of obesity on breast cancer survival may be greater than previously estimated.

Many epidemiologic studies, although not all, have shown an inverse relation between non-steroidal anti-inflammatory drug (NSAID) use and risk of incident breast cancer, but the possible influence of NSAID use on breast cancer survival has not been evaluated. We examined the association between self-reported NSAID use and survival after invasive breast cancer diagnosis among 591 postmenopausal women in a prospective study. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer death as well as all-cause mortality associated with NSAID use. There was an indication of reduced risk of breast cancer mortality and all-cause mortality for women reporting any versus no use of NSAIDs, with multivariate-adjusted HRs of 0.64 (95% CI 0.39-1.05) and 0.57 (95% CI 0.40-0.81), respectively. There was no trend of decreasing risk of death with increasing frequency of NSAID use per week. While the results from this exploratory analysis are preliminary, there is biological plausibility for such an association. Further studies should consider whether NSAIDs, which have biological activity affecting tumor promotion and progression and appear to protect against breast cancer incidence, may be associated with better prognosis after a diagnosis of invasive breast cancer.

Scope Diet in relation to breast cancer etiology has been studied widely, but results have remained inconsistent. Various dietary components including fruits, vegetables, and meat have been implicated through their effects on inflammation. Using data from the Iowa Women’s Health Study we examine prospectively the association between the dietary inflammatory index (DII) and breast cancer incidence. Methods and results DII scores were computed based on baseline dietary intake assessed by a validated 121-item food frequency questionnaire in a cohort of 34,700 women, aged 55-69 years at recruitment in 1986 and followed for incident breast cancer. During the 25-year follow-up period (1986-2011), 2910 incident breast cancer cases were identified. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI). We found positive associations between DII scores and breast cancer risk (HR for DIItertiles: T3vsT1=1.11; 95% CI 1.00, 1.22), with stronger associations in obese women (HR for DIIcontinuous: 1.05 per unit increase in DII; 95%CI 1.02,1.12; HR for DIItertiles: T3vsT1=1.35; 95%CI 1.10, 1.66, p-value for interaction=0.02). Conclusion A pro-inflammatory diet, as indicated by higher DII scores, appears to increase the risk of developing breast cancer, especially in obese postmenopausal women.