Among the highlights of research activities by members of the Adult Cancer Core have been our continued research activities related to colon and bladder cancer, several original findings related to diet and cancer, and observations on cancer occurrence in an important occupational group, California teachers.

Microsatellite instability (MSI) is now an accepted and important pathway in colon tumorigenesis, occurring in 10-15% of sporadic colon cancers and almost all hereditary nonpolyposis colon cancers. Little is known about possible environmental influences on MSI status in colon cancer. In a study of colon cancer we conducted in Los Angeles County, we found a positive association between cigarette smoking and risk of MSI+ tumors (Wu et al., Carcinogenesis, 2001). In addition, we found a significantly increased risk of MSI+ colon in association with dietary exposure to heterocyclic aromatic amines (HAA) as determined by two surrogates of high HAA exposure, preference for well-done red meat and high frequencies of certain cooking practices. These results provide a potential mechanism of linking HAA exposure and cigarette smoking to a specific subset of colon cancers.

Other than cigarettes, the main population source of potentially carcinogenic arylamines is permanent hair dyes. We earlier provided evidence that use of permanent hair dyes is a risk factor for bladder cancer, and this year demonstrated enhanced risk among individuals genetically deficient in detoxifying arylamines (Yu et al., 2002; Gago-Dominguez et al., Carcinogenesis, in press). We also provided evidence that arylamine exposure may also account for a sizable proportion of nonsmoking-related bladder cancer in the US (Skipper et al., CEBP, in press).

We provided strong evidence that dietary soy protects against breast cancer (Jakes et al., 2002; Wu et al., Carcinogenesis, 2002; Wu et al., CEBP, 2002), and may also protect against nonsmoking-related lung cancer (Seow et al., 2002). On the other hand, soy intake may lead to increased bladder cancer risk (Sun et al., 2002). We provided the first set of prospective data linking green tea intake to reduced risk of gastric and esophageal cancer (Sun et al., 2002). Earlier, we provided evidence that dietary isothiocyanates (derived almost exclusively from intake of cruciferous vegetables) protect against smoking-related, as well as nonsmoking-related lung cancer, especially among individuals genetically deficient in glutathione S-transferases (GSTs). We extended these observations on the cancer protective effect of isothiocyanates and the modifying effects of GSTs on diet-lung cancer association to colorectal cancer as well (Seow et al., Carcinogenesis, in press).

Teachers have long been suspected to be at high risk of breast cancer. The California Teachers Study (CTS) is a prospective study of 133,479 California female teachers and administrators, established in 1995-1996 with members of the California State Teachers Retirement System completing a detailed mailed questionnaire regarding possible risk factors for breast and other cancers. Cancer outcomes are identified by linkage with the California Cancer Registry. This year we demonstrated that CTS participants have a 51% higher age-standardized invasive breast cancer incidence rate and a 67% higher in-situ breast cancer incidence rate than would be expected based on race-specific statewide rates (Bernstein et al., Cancer Causes Control, 2002). CTS participants also have substantially elevated rates of endometrial cancer (rate ratio, RR = 1.72), ovarian cancer (RR = 1.28), melanoma (RR = 1.59), non-Hodgkin's lymphoma (RR = 1.53), and leukemia (RR = 1.28), but low rates of invasive cervix cancer (RR = 0.53) and lung cancer (RR = 0.66). We showed that late age at first birth can explain only a portion of the observed excess risk of breast cancer in this cohort. We are continuing to investigate what might explain the residual excess, including the possibility that some unique aspect of a teacher’s, work environment may contribute. The reasons for the excess risk of other cancers, including especially melanoma and NHL are also unknown, but being investigated.