Radiation studies We are conducting a thyroid screening study of Ukraine and Belarus residents exposed radioactive nuclides after the Chornobyl nuclear reactor accident, and a case-control study of clean-up workers exposed to radiation. In 71 leukemia cases and 501 controls, the excess relative risk (ERR) of total leukemia was 3.44/Gy; it was similar for CLL and non-CLL leukemia, ERR=4.09/Gy and 2.73/Gy, respectively. We found an increasing dose-response for incidence of acoustic neuroma in a cohort of 3112 individuals irradiated as children. Studies of pesticide exposures We evaluated permethrin, a widely used synthetic insecticide, and cancer incidence in the Agricultural Health Study, a cohort study of pesticide applicators in Iowa and North Carolina, and did not find associations between exposure and various cancers. Lung cancer We reported on the EAGLE study, a population-based case-control study in Lombardy, Italy that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer survival. A gene expression analysis of 135 fresh-frozen tissue samples of lung adenoma showed that mitotic genes known to be involved in cancer development are induced by smoking and affect survival. Testicular Cancer The US Servicemen's STEED case-control study of testicular germ-cell tumors (TGCTs) reported that exposure to endocrine-disrupting chemicals may increase TGCT. Using specimens from 28 TGCT patients, classic G-banding cytogenetic analysis and SKY were done on metaphase spreads of cultured peripheral blood lymphocytes. There was no association of cytogenetic abnormalities and TGCT. Non-Hodgkin lymphoma In a SEER-based case-control study of NHL, we found no association between use of antibiotics and risk of total NHL or any NHL subtype. Total number of surgeries and dental procedures were associated with increased risk of NHL. In a population-based case-control study of 24,728 NHL patients and 55,632 controls from Demark and Sweden, we associated personal history of systemic autoimmune diseases to increased NHL risk. Results suggested that shared susceptibility may explain a very small fraction of the increase. Studies of viruses We measured human herpesvirus-8 antibodies in 4166 children in NHANES III and found borderline associations with measures of crowding and low socioeconomic status. We showed the importance of persistence of cervical HPV infection in management strategies using data from the Natural History Study in Guanacaste, Costa Rica. We published a description of the fieldwork and rationale for a community-based, randomized clinical trial of an HPV 16 and 18 vaccine. We used samples from the Costa Rica Vaccine Trial to show that a novel PCR-based Chlamydia trachomatis detection and genotyping assay permits reliable detection of C. trachomatis serovars. Using data from ALTS, a clinical trial of women with ASCUS or low-grade squamous intraepithelial lesions (LSIL) Hybrid Capture 2, a clinical test for carcinogenic HPV DNA, cross-reacts with certain untargeted, noncarcinogenic HPV genotypes that are phylogenetically related to the targeted genotypes, but the degree of cross-reactivity may be less than previously reported. We found that cervical inflammation in the stroma and epithelium of cervical biopsies varied with HPV cofactors, type of HPV infection and risk of persistence and progression. We conducted a randomized phase 2 clinical trial of transdermal nicotine patches for classic Kaposi sarcoma (cKS). Treatment assignment was not associated with changes in cKS lesion area or elevation, HHV8 viral load or antibodies. We evaluated the association between HHV-8 and schistosomal and hepatitis C virus infections in Egypt using survey data from 965 rural households. The HHV-8 association with antischistosomal antibodies was were marginal for women, suggesting salivary and possible nosocomial HHV-8 transmission in rural Egypt. We conducted a case-cohort study of H. pylori seropositivity and esophageal and gastric cancers in Linxian, China. Risks of gastric cardia and non-cardia cancers increased with H. pylori exposure, whereas risk of esophageal squamous cell cancer was not affected. The associations between H. pylori exposure and gastric and non-cardia adenocarcinoma were comparable, in contrast to Western countries. We measured various biomarkers in HTLV-I carriers and non-carriers. Carriers had higher cleaved lymphocytes, WBCs and phosphorus levels. In carriers, antibody titer was positively correlated with lactate dehydrogenase and phosphorus levels. Provirus load among carriers was negatively correlated with hemoglobin and eosinophil proportion, and positively correlated with phosphorus. Stercoralis antibodies were not associated with HTLV-I status, antibody titer, or provirus load. Biomarkers We measured cytosine methylation (5-mC) content in genomic DNA in subjects from a bladder cancer case-control study. The lowest risk occurred in never smokers with the highest methylation, suggesting that global methylation in genomic DNA could be a useful biomarker. We examined genomic methylation of leukocyte DNA in women asymptomatic women for colorectal adenoma in the CONCeRN Study and implicated genomic methylation as a potential etiologic factor for an early stage disease. Cancer genetics Using data from the STEED study we found no evidence for an association between 15 specific 8q24 SNPs and TGCTs in heterozygotes or variant homozygotes, overall or by histology. Initial study findings from the Cancer Genetic Markers of Susceptibility genome-wide association study point to multiple loci with moderate effects associated with susceptibility to prostate cancer. We did not observed any substantial association of variations in ESR2 with prostate cancer risk in pooled data from the breast and prostate cancer cohort consortium. We found elevated gamma-glutamyltransferase (GGT) increased risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and hematopoietic cancers in a cohort of 92,843 Austrian women, including 4,884 incidence cancers. Analyses of BMI, physical activity, diet and nutrients We found increased risk of mortality in underweight women and in overweight or obese women based on BMI 10 years prior to start of follow-up in the BCDDP cohort of women. Pre-existing conditions and smoking did not modify the BMI and mortality relationship. We used data from two replicate measurements of serum nutrients in NHANES III to examine within-subject and between-subject variance. In Blacks, the within-subject to between-subject variance ratio for beta-cryptoxanthin concentration was higher relative to Whites and Mexican Americans, and the lutein + zeaxanthin ratio was higher relative to Mexican Americans. Higher income was associated with larger variance ratios for serum vitamin C and folate but smaller for vitamin A. Using PLCO data on 3,057 adenoma cases of the large bowel and 29,413 controls, we found risk of adenoma was lower in higher quintiles of total fruit intake. The protection occurred only for colon and not rectal adenoma. Diets rich in fruit and deep-yellow vegetables, dark-green vegetables, and onions and garlic reduced risk of colorectal adenoma. Using 1988 NHANES data , we found that alcohol quantity and frequency were independently associated with cause-specific mortality, including mortality from all-causes, cardiovascular disease, cancer, and other-causes. Ghana prostate cancer screening study We are investigating the contributions of genetics and lifestyle factors in prostate cancer etiology in a population-based screening study in Accra, Ghana. The study consists of 1,037 healthy men randomly selected from the population for screening with PSA testing and DRE.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP010184-06
Application #
7733740
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2008
Total Cost
$600
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lubin, Jay H; Cook, Michael B; Pandeya, Nirmala et al. (2012) The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Cancer Epidemiol 36:306-16
Kwon, Deukwoo; Vannucci, Marina; Song, Joon Jin et al. (2008) A novel wavelet-based thresholding method for the pre-processing of mass spectrometry data that accounts for heterogeneous noise. Proteomics 8:3019-29
Colbert, Lisa H; Graubard, Barry I; Michels, Karin B et al. (2008) Physical activity during pregnancy and age at menarche of the daughter. Cancer Epidemiol Biomarkers Prev 17:2656-62