Faculty Bibliography

Consumption of foods high in sugar promotes insulin production, which has been linked to endometrial carcinogenesis. We evaluated the impact of dietary intake of sugary foods and beverages, as well as added sugar and total sugar on endometrial cancer risk in a population-based case-control study, including 424 cases and 398 controls. Participants completed an interview and food frequency questionnaire, and provided self-recorded waist and hip measurements. Women in the highest quartile of added sugar intake had significantly increased endometrial cancer risk (OR = 1.84, 95 % CI 1.16-2.92). Among women with waist-to-hip ratio >/=0.85, risk was significantly higher for the highest versus lowest tertile of added sugar intakes (OR = 2.50, 95 % CI 1.38-4.52). The association with added sugar also became stronger when analyses were restricted to never users of hormone replacement therapy (OR = 2.03; 95 % CI 1.27-3.26, for highest versus lowest tertile). There was little evidence of effect modification by body mass index or physical activity. Given the high prevalence of intake of sugary foods and drinks in Western populations, additional research is warranted to confirm our findings on endometrial cancer.

Dietary variety is positively correlated with energy intake in most studies. However, the associations between dietary variety and measures of body adiposity are inconsistent in the literature, which limits the development of clear national nutrition recommendations regarding dietary variety. In the present systematic review, we critically evaluate the associations between dietary variety and measures of body adiposity among healthy adults within the existing literature. We conducted a systematic search of the MEDLINE and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to examine these associations. We identified twenty-six studies in total that investigated the associations between dietary variety and body adiposity measures. Total variety was non-significantly associated with body adiposity in most studies, while variety in recommended foods was either inversely associated (six out of ten studies) or non-significantly associated (three out of ten studies) with body adiposity. Conversely, variety in non-recommended foods (i.e. sources of added sugars and solid fats) increased the likelihood of excess adiposity in most studies (six out of nine studies). Definitions and measurement of dietary variety were inconsistent across studies and contributed to some of the discrepancies noted in the literature. In conclusion, among the studies that met the inclusion criteria for the present review, dietary variety was inconsistently associated with body adiposity in diverse populations. Using consistent and specific definitions of dietary variety may help provide further insight into the associations between dietary variety and excess adiposity before definitive public health messages are made.

Higher blood glucose is hypothesized to increase colorectal cancer risk. Longitudinal associations of hyperglycemia with incident colorectal cancer were investigated among the Framingham Heart Study Offsprings (n=4192; n events=136; 1971-2008). Fasting insulin and glucose were estimated from blood samples; demographic, smoking, activity and dietary information was obtained during interviews. Time-dependant survival analyses were used to compute hazard ratios (HR) and 95% confidence interval (CI) for colorectal cancer incidence, using SASv9.2. After adjusting for age, sex, smoking, alcohol and physical activity, hyperglycemia (>110 mg/dl) was associated with 2.2-fold increase in risk of incident colorectal cancer (HR: 2.21; CI:1.5-3.2). Risk was approximately 2-fold higher among persons with hyperinsulinemia (HR:2.1; CI:1.1-3.9) and poor long-term glycemic control measured by hemoglobin A1c (HR:2.2; CI: 1.1-4.5) for tertile 3 vs. 1 in adjusted models. Additionally, persons with 5-10y, 10-20y, 20+ y of hyperglycemia had a significant 1.8-, 2.5 and 3.5-fold increased risk of colorectal cancer, respectively. In conclusion, disturbances in glucose metabolism appear to increase risk of colorectal cancer. These data suggest that risk increases with the duration of exposure to hyperglycemia

Obesity-induced aberrations in glucose metabolism are associated with cancer risk. We investigated prospective associations of hyperglycemia with incidence of cancers associated with obesity, in the Framingham Heart Study Offsprings (n=4615; n events=787; 1971-2008; mean age 66.8y in 2008). Serum insulin and glucose were estimated from fasting blood; lifestyle and demographic information was obtained from in-person interviews. Time-dependant survival analyses were used to compute hazard ratios (HR) and 95% confidence interval (CI) of cancer incidence, using SAS. After adjusting for age, sex, smoking status, alcohol and physical activity, hyperglycemia (>110 mg/dl) was associated with 27% increased risk of overall obesity-related cancer incidence (HR:1.27; CI:1.1-1.5). Risk was 47% (CI:1.1-1.9) and 54% (CI:1.1-2.1) higher among persons with hyperinsulinemia and poor long-term glycemic control measured by hemoglobin A1c, respectively for tertiles 3 vs 1. Associations were stronger in "ever" smokers (HR:1.41; CI: 1.1-1.8). In gender stratified analyses, associations were stronger among females. Hyperglycemia for 10-20y and 20+y increased risk by 44% (CI: 1.1-1.6) and 86% (CI: 1.5-2.2) of overall obesity-related cancers, respectively. Hyperglycemia, particularly poor long-term glycemic control, is a 'high-risk' condition for obesity-related cancer incidence

OBJECTIVES: While diabetes has been linked to several cancers in the gastrointestinal (GI) tract, findings have been mixed for sites other than colorectal and liver cancer. We used the Women's Health Initiative (WHI) data and conducted a comprehensive assessment of associations between diabetes and GI malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal). METHODS: A total of 145,765 postmenopausal women aged 50-79 enrolled in the WHI were followed for a mean 10.3 years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between GI cancers and diagnosed diabetes, including its duration and treatment. RESULTS: Diabetes at enrollment was associated with increased risk of liver (HR = 2.97; 95 % CI, 1.66-5.32), pancreatic (HR = 1.62; 95 % CI, 1.15-2.30), colon (HR = 1.38; 95 % CI, 1.14-1.66), and rectal (HR = 1.87, 95 % CI: 1.22-2.85) cancer. Diabetes severity, assessed by duration or need for pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic, and rectal cancer, but not colon cancer. There was no statistically significant association of diabetes with biliary, esophageal, and stomach cancers. CONCLUSION: Type 2 diabetes is associated with a significantly increased risk of cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The suggestion that diabetes severity further increases these cancer risks requires future studies.

BACKGROUND: Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk. METHODS: We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case-control study. Cases were women with newly diagnosed epithelial ovarian cancer, older than 21 years, able to speak English or Spanish, and residents of six counties in New Jersey. Controls met same criteria as cases, but were ineligible if they had both ovaries removed. A total of 205 cases and 390 controls completed a phone interview, food frequency questionnaire, and self-recorded waist and hip measurements. Based on dietary data, we computed the number of servings of dessert foods, non-dessert foods, sugary drinks and total sugary foods and drinks for each participant. Total and added sugar intakes (grams/day) were also calculated. Multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for food and drink groups and total and added sugar intakes, while adjusting for major risk factors. RESULTS: We did not find evidence of an association between consumption of sugary foods and beverages and risk, although there was a suggestion of increased risk associated with sugary drink intake (servings per 1,000 kcal; OR=1.63, 95% CI: 0.94-2.83). CONCLUSIONS: Overall, we found little indication that sugar intake played a major role on ovarian cancer development.

Laboratory evidence suggests a plausible role for dietary fat in breast cancer pathophysiology. We conducted a systematic literature review to assess the epidemiological evidence on the impact of total dietary fat and fat subtypes, measured pre- and/or postcancer diagnosis, in relation to breast cancer-specific and all-cause mortality among breast cancer survivors. Studies were included if they were in English, had a sample size >/=200, and presented the hazard ratio/rate ratio for recurrence, diseasespecific mortality, or all-cause mortality (n = 18). Although the results are mixed, most studies suggested that higher saturated fat intake prediagnosis was associated with increased risk of breast cancer-specific and all-cause mortality. Postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of all-cause mortality. Higher monounsaturated fat intake before and after diagnosis was generally associated with increased risk of all-cause and breast cancer-specific mortality, albeit the majority of the studies were statistically nonsignificant. Two studies evaluating omega-3 fat intake suggested an inverse association with all-cause mortality. Although there were too few studies on fat subtypes to draw definitive conclusions, high consumption of saturated fat may exert a detrimental effect on breast cancer-specific and all-cause mortality, whereas omega-3 fat may be beneficial. The inconsistent and limited evidence warrants research to assess the impact of consumption of fat subtypes on breast cancer recurrence and mortality. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Although obesity is a well-known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colo-rectal cancer. We note that the evidence overrepresents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors.

The hypothesis is that fiber protects against colorectal cancer because of various biologic properties. Although several human studies have examined the relationship between fiber and colorectal carcinogenesis, the association remains unclear. This review evaluates key epidemiologic research in large populations conducted since 2003. With a combined analysis of 9 studies, results are mixed. Four studies show a statistically significant reduced risk of developing colorectal cancer with increased dietary fiber intake, and 5 studies show no association. On the basis of these equivocal findings, it cannot be concluded that a protective association exists between increased dietary fiber intake and reduced colorectal cancer risk.