This is a request for continued funding of a residential cohort of 63,257 middle-aged and older (45-74 years) Singapore Chinese men and women accrued between 1993 and 1998. The primary goal of this long-term, population-based cohort study is to elucidate the role of diet and its interaction with genetic factors in the causation of human cancer. At recruitment, each study subject was interviewed in person by a trained interviewer using a structured questionnaire that emphasized current diet assessed via a validated, 165-item food frequency questionnaire. Beginning in April 1994, a random 3% sample of cohort participants were asked to provide blood or buccal cell, and spot urine samples. We extended this biospecimen collection to all surviving cohort participants starting in January 2000. By May 2004, all surviving cohort subjects had been contacted, and biospecimens were collected from 31,318 subjects, representing a consent rate of about 60%. We also asked for blood/buccal/urine specimens from all incident cases of female breast and colorectal cancers beginning in April 1994. To date, the number of cancer cases with pre- or post-diagnostic biospecimens totals 686 (304 female breast, 223 colon, 159 rectum). Between July 1999 and December 2003, all surviving cohort subjects were recontacted for consent to a telephone interview to update information on selected exposures and medical history. Interviews were completed on 52,326 subjects, representing a consent rate of over 90%. The cohort has been passively followed for death and cancer occurrence through regular record linkage with the population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths. The observed numbers of incident cancers and deaths within the cohort are comparable to corresponding expected numbers based on age-sex-specific incidence rates for all Chinese in Singapore. We will continue to take advantage of this cohort to examine potential cancer protective dietary factors that are rarely consumed among the well-studied occidental populations. Our specific aims for the next 5 years are: (1) to assess the role of tea intake in cancer protection, with consideration for the type of tea drunk (green vs. black tea) and for individual susceptibility factors including key polymorphic genes controlling the 3 major excretion pathways (O-methylation, glucuronidation, sulfation) for tea polyphenols; and (2) to assess the potential roles of genes involved in repair of DMA damage and in cell cycle regulation in modifying a given association between tea as well as other identified dietary protective factors and cancer.