Cancer genetics Information from almost 60,000 men and women who participated in genome-wide association studies underscores the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset events. Genetic variation in lipid metabolism genes, ALOXE3 rs3027208 and terbufos, in Agricultural Health Study (AHS) may modify pesticide associations with prostate cancer;the results require replication. Because genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC), a model to predict a patient's probability of SVR based on both IL28B genotype and clinical variables had improved prediction using HALT-C Trial data. Genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance showed evidence of a supra-additive (quadratic) model using data from the Urban Health Study. A pooled analysis of 26 observational studies on the survival of women with epithelial ovarian cancer having a germline mutation in BRCA1or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. Endogenous Hormone A prospective casecontrol study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found that more extensive 2-hydroxylation of parent estrogens is associated with lower risk and less extensive methylation of potentially genotoxic 4-hydroxylation pathway catechols, and is associated with higher risk of postmenopausal breast cancer. An investigation of how estrogens/estrogen metabolites relate to Westernization using 12-h urines from premenopausal luteal and postmenopausal Chinese, Japanese, and Filipino women from a case-control study found that estrogen metabolism decreased 2-hydroxylation, rather than total estrogen production, which may explain the elevated risk of breast cancer in Western, compared to Asian, societies. Lung Cancer A case-control study of 198 lung cancer deaths and 562 incidence density-sampled controls found that diesel exhaust exposure causes lung cancer in humans based on quantitative historical exposure data with control for smoking and other confounders. Esophageal Cancer Pooling of 12 case-control studies from the Barretts Esophagus and Esophageal Adenocarcinoma Consortium examined how delivery rate of alcohol and smoking modifies the strength of odds ratio (OR) of cancer trends with total exposure. Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases. Environmental Exposures. Three studies initiated in the 1970s had continued long-term follow-up of women exposed in utero to diethylstilbestrol (DES) and unexposed controls. 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Two cohort and two nested case-control studies of childhood cancer survivors were pooled and found that radiation dose-related RRs of thyroid cancer increased approximately linearly for 10 Gy, leveled off at 10-15-fold for 10-30 Gy then declined, but remained elevated for doses 50 Gy. A nested case-control study conducted in a cohort of Ukrainian cleanup workers for the 1986 Chernobyl nuclear power plant accident found that exposure to low doses and low-dose-rates of radiation was associated with an increase in risk of leukemia, and CLL and non-CLL appear equally radiosensitive. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides that were missing from incomplete response to a second questionnaire in the AHS. Multiple imputation reduced bias and increased precision over other missing data approaches. Several insecticides were observed to increase the risk of aggressive prostate cancer in the AHS. Future follow-up will be needed to confirm these results and to understand how each chemical impacts prostate carcinogenesis. Kidney Cancer US Kidney Cancer Case-Control Study found smoking to be associated with kidney cancer only in nonobese individuals and those with no history of hypertension. Colorectal Cancer Data from SEER program is used to illustrate development of a prognostic model to predict the absolute risk of mortality from colorectal cancer and from other causes for an individual with specific covariates. It incorporates previously developed methods for competing risk modeling along with an imputation method for missing causes of death and evaluates the model discriminatory and calibration accuracy by time-dependent area under the receiver operating characteristic curve and calibration plot. Microbiota From a small pilot study it was determined that reproducibility of the distal gut microbiota, -glucuronidase and -glucosidase bioactivities for epidemiologic or clinical studies requires a sufficient quantity of rapidly chilled or frozen specimens collected in phosphate buffered saline at pH70. A pilot study assessed reproducibility and associations of microbial diversity and composition in faecal microbial DNA. Collecting samples with two Polymedco and two Sarstedt devices for various parts of a stool, both devices provided good reproducibility on overall microbial diversity and classification for the major phyla, but not for minor phyla. Cancer Screening and History Several biomarkers that had been shown to be predictive of ovarian cancer with CA 125 in prediagnostically collected sera, however, in postdiagnostically collected sera, the addition of the biomarkers with CA 125 did not improve diagnosis beyond CA 125 alone using PLCO data. 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010184-10
Application #
8565446
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2012
Total Cost
$1,838,536
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Lubin, Jay H; De Stefani, Eduardo; Abnet, Christian C et al. (2014) Mate drinking and esophageal squamous cell carcinoma in South America: pooled results from two large multicenter case-control studies. Cancer Epidemiol Biomarkers Prev 23:107-16
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