We published a paper describing the kin-cohort method in detail and showing estimates for penetrance when phenotype is described as the earlier of breast or ovary cancer. We published a paper that used an extension of the kin-cohort method to show from the Washington Ashkenazi Study that survival after diagnosis of breast cancer did not differ appreciably between carriers and non-carriers of BRCA1 and BRCA2 mutations. We published a paper that described the prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jews as a function of personal and family history. We are studying the effect of modifying factors and family history on penetrance. We are collaborating with Israeli scientists on a case-control study of cancer of the ovary to identify factors that modify the effects of BRCA1 and BRCA2. We published or prepared several manuscripts on human papillomavirus (HPV) and its relation to cervical dysplasia. One showed that cytologically normal women who tested positive for HPV DNA at enrollment were almost 4 times more likely to develop low grade squamous intraepithelial lesions (SIL) and almost 13 times more likely to develop high-grade (SIL) during follow up than women who were initially HPV-negative. In a population-based study of 8460 women, cervicography was compared to cytologic testing. Particularly for women above age 50, cytologic testing had higher sensitivity for detecting high-grade SIL or cancer than did cervicography. We also showed that using a cut-point of 1.0 pg/ml using the Hybrid Capture II (HC II) test detected 100% of cancers and 88% of high grade SIL. Higher detection thresholds (>=10pg/ml) were insensitive; lower levels of detection (<= 1 pg/ml) proved clinically non-specific with no additional sensitivity. We are planning a trial of a vaccine against HPV infection in Costa Rica; the clinical outcome will be development of dysplasia. In a cohort of 1293 healthy nondisabled older people, higher interleukin-6 levels and higher C-reactive protein levels were associated with overall mortality as well as cardiovascular and non-cardiovascular causes of death. Several studies are currently underway to study the role of endogenous hormones for reproductive cancers. We conducted assay reliability studies to determine which laboratories perform well and to assess the precision and usefulness of hormone assays for epidemiologic studies. We examined the variability and reproducibility of nine androgen assays at four laboratories using serum from both male and female serum. We also examined the variability and reproducibility of insulin like growth factors at three laboratories. The reproducibility and validity of radio immunoassays for urinary hormones and metabolites were evaluated. Measurements of sex hormones in serum using radioimmunoassay and mass spectrometry were compared. We haveparticipated in the design and evaluation of quality control as study samples were assayed for endogenous hormones and micronutrients including androgens, estrogens, growth factors, carotinoids and fatty acids. In a large case control study, serum homocysteine was found to be a predictor of invasive cervical cancer. Compared with women in the lowest homocysteine quartile, women with higher homocysteine levels had two to three times the risk of invasive cervical cancer. The influence of cancer stage and treatment of serum on red blood folate measurements was evaluated in this case control study of cervical cancer. A ten-year cohort study of 145 men with chronic hepatitis from hepatitis B virus in Qidong, Jaingsu Province,China revealed that those with elevations of aflatoxin metabolite M1 in the urine had an increased risk of hepatocellular carcinoma. Infection with hepatitis C virus also increased the risk of hepatocellular carcinoma.
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