Metabolites. Obesity and lifestyle exposures, such as poor diet, physical inactivity, and smoking have been implicated in carcinogenesis, but underlying molecular mechanisms remain, in many cases, unclear. To study these molecular mechanisms, we have performed metabolic profiling on individuals with colorectal, prostate, gastric, and breast cancer, in addition to matched controls. Using advanced high dimensional methods, we have started to develop metabolic signatures of disease development and diagnosis. Furthermore, detailed analysis of metabolite variability has provided details on how to correctly design future epidemiological studies, in terms of number of individuals and measurements needed to detect realistic effect sizes. Body weight,Physical Activity and Nutrition. A systematic review of reported hazard ratios (HRs) of all-cause mortality for overweight and obesity relative to normal weight in the general population was conducted among 97 studies, providing a combined sample size of about 2.88 million individuals. Relative to normal weight, both obesity (all grades) and grades 2 and 3 obesity were associated with significantly higher all-cause mortality, grade 1 obesity overall was not associated with higher mortality, and overweight was associated with significantly lower all-cause mortality. Associations between 24-hour recall energy consumed in beverages and a variety of meal and dietary attributes to quantify the contribution of beverage consumption to the energy content of diets in free-living individuals consuming their self-selected diets were examined in the NHANES 2003-2008. Higher 24-hour beverage energy intake was related to higher energy intake from nonbeverage foods, quality of food selections, and distribution of 24-hour energy into main meal and snack episodes. In the Weight Loss Maintenance Trial, estrogen hormone levels decreased less after weight loss for obese black women than for obese white women. In a pooled analysis of 654,827 individuals, more leisure time physical activity was associated with longer life expectancy across a range of activity levels and body mass index (BMI) groups. Endogenous Hormones. A study of associations of green tea intake with urinary estrogens and estrogen metabolites in a cross-sectional sample of healthy Japanese American women (n= 119 pre- and n= 72 postmenopausal women) found that intake of green tea may modify estrogen metabolism or conjugation. In data from the NIH-AARP Diet and Health Study and the PLCO, risk factors for ovarian cancer differed between nulliparous and parous women. Multiple Myeloma. A study of 9,399 multiple myeloma Swedish patients found that the development of thrombosis was associated with significantly poorer survival. Lung Cancer. In the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (PLCO), the use of a lung cancer risk model was more sensitive than simple NLST criteria for lung-cancer detection. In PLCO, an inflammation score developed using 4 serum inflammatory markers increased lung cancer risk stratification beyond that from using smoking and other epidemiologic risk factors. Sex-smoking interaction in association with lung cancer risk within a population-based case-control study, the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study, was assessed. A higher female susceptibility to tobacco-related lung cancer was not found. In EAGLE it was found that the role for reproductive and hormonal factors in the etiology of lung cancer in women who continue to produce estrogens have a lower lung cancer risk. Liver Cancer. There has been a dramatic decrease in liver cancer incidence Qidong City, China, where hepatitis B prevalence is above 10%. A reduction in exposure to aflatoxin as a result of dietary changes from corn to rice is a likely cause of the current reductions in liver cancer incidence. Environmental Exposures. We developed a machine-learning algorithm for determining diesel exposure, and developed an efficient sampling plan for validating the algorithm against expert exposure assessors. An evaluation of differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident found long term differential gene expression in relation to individual I-131 doses and identifies a set of genes potentially important in radiation carcinogenesis. Kidney Cancer The US Kidney Cancer Case-Control Study (KCCS) and a European case-control study were used study risk factors by subtype of renal cancer carcinoma (RCC). Results showed distinct age, sex and racial distributions for renal cancer subtypes and that that the obesity RCC association differs by histology. The KCCS was used to investigate RCC risk in relation to chronic renal failure. Chronic renal failure was found to be a strong risk factor for RCC, particularly among black and non-diabetics. HPV. Among men and women aged 14 to 69 years in the US National Health and Nutrition Examination Survey 2009-10, the overall prevalence of oral HPV infection was 6.9%, and the prevalence was higher among men than among women and variety by with a peak 30-34 yrs and 60-64 yrs. In the Costa Rica Vaccine Trial (CRVT), anal HPV is common among young women, even those who report no anal sex, and was associated with cervical HPV infection. The association of human papillomavirus type 16 (HPV16) DNA methylation with age, viral load, viral persistence and risk of incident and prevalent high grade CIN (CIN2+) in serially collected specimens from the Guanacaste, Costa Rica cohort was studied. Elevated levels of HPV16 DNA methylation may be useful to predict concurrently diagnosed as well as future CIN2+. In 388 unvaccinated women in the control arm of the CRVT HPV16 seropositivity was measured using three serological assays. Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, with differing cutoffs for immune protection. Anal Cancer. In the US HIV/AIDS Cancer Match Study the impact of the HIV epidemic on trends on the increasing anal cancer incidence during 1980-2005 was found strongly influenced by the HIV epidemic in males but not in females. Multiple Cancers. Using the Transplant Cancer Match Study and nonparametric competing risk methods for cumulative incidence of cancer after transplantation for 2 periods (1987-1999 and 2000-2008), it was found that subgroups of transplantation recipients have a high absolute risk of some cancers and may benefit from targeted prevention or screening. In a US record linkage study with incident cancers and deaths in 372 364 people with AIDS (1980-2006), deaths with AIDS and cancer were mostly attributable to cancer. Cancer risk after blood transfusion evaluated in a US case-control study using 552,951 elderly cases and 100,000 controls, was elevated 0 to 12 months after blood transfusion and associated with multiple transfusions, possibly due to reverse causation. About 203 tagging SNPs of 22 genes on 9p21.3 were examined in 8 cancers from case-control studies and found that genetic variants in CDKN2A, and possibly nearby genes, may be associated with oesophageal squamous cell carcinoma and several other tumors.
|Meulepas, Johanna M; Hauptmann, Michael; Lubin, Jay H et al. (2018) Is there Unmeasured Indication Bias in Radiation-Related Cancer Risk Estimates from Studies of Computed Tomography? Radiat Res 189:128-135|
|Flegal, Katherine M; Graubard, Barry I; Yi, Sang-Wook (2017) Comparative effects of the restriction method in two large observational studies of body mass index and mortality among adults. Eur J Clin Invest 47:415-421|
|Nyante, S J; Graubard, B I; Li, Y et al. (2012) Trends in sex hormone concentrations in US males: 1988-1991 to 1999-2004. Int J Androl 35:456-66|