We published a paper with Israeli scientists on a case-control study of ovarian cancer to identify whether reproductive factors that reduce the risk in carriers are also protective in carriers. In non-carriers we found that oral contraceptives and parity reduce the risk of ovarian cancer, as expected. Among carriers, there was no evidence of protection from oral contraceptives, but there was support for reduction in risk with increasing parity. We published a paper that estimated the penetrance of BRCA1 and BRCA2 for breast cancer pooling data from studies of Ashkenazi Jews in Washington, New York, and Toronto. We showed how the kin-cohort approach can be extended to estimate residual familial correlation of the disease after accounting for effect of the measured genes. Application of the method on the Washington Ashkenazi Study revealed significant effect of family history among non-carriers of BRCA1/BRCA2 mutations. We prepared the protocol for a placebo-controlled trial of a virus-like particle and chimeric virus-like particle vaccine against HPV-16 (human papillomavirus, type 16) infection in Costa Rica; the clinical outcomes will be development of dysplasia and persistence of HPV-16 infection. The protocol was approved by several, but not yet all, of the required oversight committees. We published or prepared several manuscripts on human papillomavirus (HPV) and its relation to cervical dysplasia from our natural history study in Guanacaste, Costa Rica. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. Preexisting HPV-16 was generally associated with an increased risk for subsequent acquisition of other types. HPV-16 did not affect the persistence of concomitant infections, regardless of type. These findings suggest that the prevention or removal of HPV-16 is not likely to promote the risk of infection with other types, a theoretical concern with current vaccination efforts. Further, our data provide epidemiologic evidence, from a population-based study, that different HPV16 variants have different oncogenic potential. Combined with our previous finding that HPV16 infection (all variants combined) in our Guanacaste population is associated with a 710-fold increased risk of cervical cancer, the present finding that those infected with non-European-like (NE) variants of HPV16 are 11 times more likely than those infected with the prototype HPV16 virus to be diagnosed with cervical cancer suggests that the overall risk associated with infection with NE variants of HPV16 is indeed large. In a paper with a clinical focus based on our work in Costa Rica, we found that optimized Cervigram classification improved performance slightly over a single interpretation, suggesting the limits of static visual screening. We also found that among women positive for high-risk HPV types, 44% of HSIL/CA (high-grade squamous intraepithelial lesions or cancer) could be attributed to multiparity (>=3 pregnancies) and/or smoking. Among HPV-positive women, multiparity and smoking are risk factors for HSIL/CA. We submitted a paper that shows that in China, where the mean body mass index (BMI) is lower than in Western countries, higher levels of BMI, intake of animal proteins, height and inactivity independently predict waist-hip ratio, and therefore, may be predictors of diabetes, cardiovascular disease, and cancer. A case-control study at five study sites in the US found that women with higher levels of serum homocysteine, as measured at least six months after the end of chemotherapy. Had a higher risk of invasive cervical cancer. A case-control study of prostate cancer in Shanghai, China, where rates are low, found evidence that higher levels IGF-I, IGFBF-3, and IGFBP-1, but not IGF-II, are related to risk. We submitted the results of a meta-analysis that in suggests that the GSTM1 null genotype may be related to a moderate increase in risk of bladder cancer. We reported that GSTT1 null, GSTM1 null, and CYP1A1 462Val genotypes involved in tobacco metabolism did not increase risk of oral cancer in Puerto Rico, although for GSTM1 null the risk of oral cancer associated with tobacco use was modified. In the same study, we reported that folate intake was associated with a reduction in the risk of oral cancer, almost entirely due to consumption of fruit, with no effect of methionine intake, serum homocysteine or MTHFR genotype. We published the results of a study describing the ability of laboratories to reproduce findings of SV40 virus in tumor tissue. In a small study of postmenopausal women and premenopausal women in either the mid-follicular or mid-luteal phase of the menstrual cycle, we showed that a single sample of androstanediol glucuronide, dehydroepiandrosterone, dehydroepiandrosterone sulfate and androsterone glucuronide can be used to determine mensutrual phase or menopausal status of women. A laboratory reproducibility study of sex hormone binding globulin (SHBG) and bioavailable testosterone and estradiol found poor reproducibility over time. Another study, however, found that SHBG measurement in EDTA plasma markedly increased reproducibility. Using data from controls in a case-control study of Asian women living in California and Hawaii, we found that levels of estrogen and SHBG did not differ between women born in Asia and born in the West; however, Asian-born women has higher levels of DHEA. Results of a laboratory study in men suggested that a single sample can be used to discriminate between levels of some male hormones in a way that is useful in case-control studies; however, improvements in measurements are required before assays for other hormones will be useful.
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