Publication list via PubMed

General Research Interests

My research focuses on the association of dietary constituents with the risk of cancer, and the interaction of diet and nutrition with other external factors (infectious agents, exogenous hormones) and host factors (steroid hormones, genetic polymorphisms, growth factors, weight) on cancer development.

Ongoing Research Activities

Studies of human papillomavirus. Human papillomavirus infection has been identified as a primary causal agent in (uterine) cervical dysplasia and carcinoma, but the virus is also detected with some frequency among women who are cytologically normal, and high-grade dysplasia and cancer occur only among a fraction of infected women. Of critical scientific and public health importance is whether the presently "established" risk factors for cervical neoplasia, such as sexual activity and tobacco smoking, are HPV cofactors that modify the progression of HPV infection to cancer or are simply correlated with viral infection. Prompted by the availability of a new HPV DNA amplifying technique, polymerase chain reaction, we initiated our first case-control study of risk factors for pre-malignant changes in cervical epithelium in the early 1990s, with a special emphasis on diet. Our results support existing evidence that high plasma levels of antioxidants may reduce the risk of cervical dysplasia independent of HPV infection, and that women with high CYP1A1 gene inducibility or low GSTM1 activity may be at greater risk of cervical dysplasia. Most recently, we found that an increase in viral copy number among women infected with intermediate- and high-risk HPV types may be important to the development and progression of cervical disease. We are presently establishing a multiethnic cohort of 1,150 HPV-positive women for long-term follow-up to identify factors that influence the persistence or resolution of HPV infection of the uterine cervix. The project's specific aims are to study the association of the dietary intake of fruits and vegetables and the plasma levels of carotenoids, tocopherols, and vitamin C with HPV persistence; and to examine the role of HPV type, viral quantity, and multiple HPV infections in HPV persistence. The identification of these factors may provide insight into the natural history of HPV infection and may improve the ability to characterize women who are at greatest risk for developing HPV-associated neoplasia.

Studies of hormone-dependent cancers. The biological interplay between hormones, diet, and metabolism on the risk of cancer in women has been a longstanding interest of our research team, including etiologic investigations of ovarian and uterine cancers, and a dietary intervention study of breast cancer. In a case-control study of endometrial cancer we found a positive association between dietary fat intake (all components) and risk, but only among women who were above the median body mass index. High-fat foods were positively associated with risk, whereas cereals, legumes, vegetables and fruits were inversely associated with risk. Consistent with these dietary findings, higher levels of cholesterol oxidation products were found in the plasma of endometrial cancer cases compared with matched controls. In a separate analysis, fiber consumption (whether from cereals, vegetables or fruits) was inversely associated with risk, as was consumption of soy products and other legumes, suggesting a possible protective effect of phytoestrogens.

We have recently completed a multi-center case-control study of diet and ovarian cancer in collaboration with the University of Southern California among the various ethnic groups in the two geographic areas. Our objective is to determine whether the substantial ethnic differences in ovarian cancer incidence reflect ethnic variation in known risk factors, such as pregnancy history and oral contraceptive use; or whether differences in dietary exposure to fat or lactose, or genetic susceptibility, are also important determinants of this disease. The establishment of enzyme susceptibility markers for ovarian cancer would have implications for cancer screening activities and the understanding of the biology of this fatal disease. In this study we will test the relation between ovarian cancer risk and genetic defects in enzymes responsible for the metabolism of galactose.

Through a sub-contract, we are participating in the Women's Intervention and Nutrition Study, a dietary intervention trial to determine whether dietary fat reduction in post-menopausal women with breast cancer will decrease the relapse rate and prolong disease-free survival.

Hawaii Tumor Registry activities. Our group administers the Hawaii Tumor Registry, which has been part of the Surveillance Epidemiology and End Results (SEER) Program of the National Cancer Institute since its inception in 1973. The registry provides complete cancer reporting for the entire state and serves as a resource for nearly all epidemiologic research activity and cancer control activities in Hawaii. This racially diverse database has been invaluable in demonstrating ethnic variations in cancer incidence and survival.