The Adult Cancer Research Core published or has “in press” 46 papers pertinent to the Center in the past year, including several that were especially noteworthy for their public health significance. Twenty-five of these publications involved multiple core members.

Members of the Core (Ross, Yu, Coetzee), in collaboration with investigators at NIEHS (London) and elsewhere demonstrated in a prospective study in Shanghai, China (the Shanghai Cohort Study) that a urinary biomarker of isothiocyanate exposure predicts a reduction in lung cancer risk in middle-aged Chinese men. Core members had previously participated in the validation of this marker which measures a class of chemicals found in cruciferous vegetables, which are potent anti-cancer agents in animal models. This study also demonstrated convincingly that this protective effect is substantially modified by glutathione S transferase genotypes, which are involved in metabolism and excretion of isothiocyanates (London et al., Lancet 356:724, 2000).

A collaborative effort by Core members (Ross, Yu) in the past year provided epidemiologic evidence for the first time that non-steroidal anti-inflammatory drugs may reduce bladder cancer incidence, compatible with their effect on bladder cancer occurrence in animal models (Br J Cancer 82:1364, 2000). In the same study, this collaboration provided the most convincing evidence to date that regular use of permanent hair dyes may increase bladder cancer risk in women (Int J Cancer (in press)).

The Core made several other novel observations in the past year regarding gene-gene and gene-environment interventions. For example, we showed that the effect of estrogen replacement therapy on endometrial cancer risk can be substantially modified by CYP17 genotype (Coetzee, Pike, Henderson), which is involved in a critical step in estrogen biosynthesis. Dr. Sue Ingles laboratory in collaboration with the laboratory of Dr. Gerry Coetzee and in conjunction with other Core members (Ross, Yu), on the other hand, demonstrated preliminarily an interaction between androgen receptor genotype and PSA genotype, a gene transactivated by the androgen receptor in the prostate, in altering prostate cancer risk (Xue et al., Cancer Res 60:839, 2000).

Finally another critical observation made by a Core scientist (Mack) in the past year, based on observations related to patterns of breast cancer occurrence in twins, is that a substantial proportion of human breast cancer may show a different model of genetic susceptibility than the classic Knudsen “multihit” pattern of risk (Nat Genet 26:411, 2000).

The Core remains extremely well funded but two new grants, in particular, stand out as particularly important to achieving Core goals. One involving Core members Bernstein and Haile seeks to understand the potential interaction between mutations in the ataxia-telangectasia (AT) gene (involved in radiation damage repair) and radiation exposure to the breast and breast cancer risk. A second, for which we have received preliminary notification of funding, will collect blood samples on all consenting members of the African-American and Latino components of the Hawaii-Los Angeles Multiethnic Study, a prospective study which includes 100,000 combined members of these two racial-ethnic groups (Henderson, Pike, Coetzee, Ross). This sample collection will allow detailed investigations of “exposure” biomarkers, genetic predisposition and gene x environment interactions in the etiology of cancer and other chronic diseases in these two underserved populations. Both of these studies will be funded by the National Cancer Institute.