Among the highlights of research activities by members of the Adult Cancer Core have been the research activities related to bladder, lung and colon cancer etiology, as well as ongoing methodologic research to enhance the ability to further assess environmental risk factors for cancer, both overall and in conjunction with genetic risk factors.

Many chemical components of hair dyes are bladder carcinogens in animals, and hairdressers (who are occupationally exposed to hair dyes) are known to experience increased bladder cancer risk. During the past year, this research provided the first set of epidemiological data that convincingly link personal use of permanent hair dyes to bladder cancer development (Gago-Dominguez et al., 2001a, 2001b). It was also shown that, contrary to expectations, women have higher smoking related bladder cancer risk than men (i.e., for a given amount and duration of smoking, women have higher risk) and this observation was confirmed with biomarker data, showing that for a given amount of smoking, women have higher levels of both 3- and 4-ABP hemoglobin adducts than men (Castelao et al., 2002).

Isothiocyanates (ITCs) are potent chemopreventive agents against lung cancer in animals. Humans are exposed to ITCs primarily through intake of cruciferous vegetables. These researchers previously had played key roles in the development and validation of a urinary biomarker of ITC for use in epidemiological studies (Chung et al., 1998; Seow et al., 1998). The researchers then provided the first set of human data linking exposure to ITC with protection against lung cancer and showed that risk was substantially modified by GSTM1 genotype (London et al., 2000). In the last year, the first observation in Chinese men in Shanghai to lung cancer was extended in Chinese women of Singapore (Zhao et al., 2001).

The relationships were evaluated between several dietary risk factors, genetic risk factors and the interrelationships of these in modifying risk of colorectal adenomas, which are precursor lesions for colorectal cancer (Cortessis et al., 2001; Ingles et al., 2000; Wang et al., 2001; Levine et al., 2001, Liu et al., in press). In particular what was shown was the risk modifying effect of glutathione transferases in modifying the protective effect of broccoli (?ITCs) on risk (Lin et al., in press) and of epoxide hydrolase in modifying risk of smoking and meat consumption (?HAAs) on risk of colorectal adenomas.

In terms of methodology, an efficient semi-automated methodology for SNP (single nucleotide polymorphism) genotyping (Makridakis and Reichardt, 2001) was published. The latter may be of significance in molecular epidemiologic investigations with large numbers of samples to be genotyped for multiple SNPs.

The MS.AP-PCR technique was used to analyze methylation alterations at GC rich regions in the genome in metachronous tumors and their derived cell lines from patients with transitional cell carcinoma of the bladder (Markl et al., 2000). The methylation status of the majority of evaluable sequences (83%) remained unchanged in the tumors from both patients relative to a panel of normal urothelium samples obtained from individuals free of bladder disease). Surprisingly, few additional changes were observed in methylation patterns in cell lines derived from the tumors. The investigation provided the first serial as well as parallel quantitation of the global epigenetic stability in two independent bladder cancer cell genomes over the course of progression and in culture. In addition, the investigation provided the first direct comparison of the epigenetic and genetic patterns on a global scale showing, quite surprisingly, that the epigenetic pattern was quite stable in vivo and in vitro over time in an individual.