THE SINGAPORE COHORT STUDY OF DIET AND CANCER

申请者描述(由申请人提供)：申请继续资助1993至1998年间在新加坡居住的63,257名中年及以上(45-74岁)的华裔男女。这项基于人群的长期队列研究的主要目标是阐明饮食及其与遗传因素的相互作用在人类癌症病因中的作用。在招募时，每个研究对象都由一名训练有素的面试者进行面谈，使用结构化问卷，强调通过有效的165项食物频率问卷评估的当前饮食。 从1994年4月开始，随机抽取3%的队列参与者，要求他们提供血液或口腔细胞，以及现场尿样。从2000年1月开始，我们将这一生物标本收集扩展到所有幸存的队列参与者。截至2004年5月，已联系了所有幸存的队列受试者，并从31,318名受试者中收集了生物检材，同意率约为60%。我们还要求从1994年4月开始的所有女性乳腺癌和结直肠癌病例的血液/口腔/尿液样本。到目前为止，诊断前或诊断后的癌症病例总数为686例(304例女性乳房，223例结肠癌，159例直肠)。 在1999年7月至2003年12月期间，重新联系了所有幸存的队列受试者，以获得同意接受电话采访，以更新有关选定接触情况和病史的信息。完成了对52,326名受试者的访问，同意率超过90%。 通过与新加坡人口癌症登记处和新加坡出生和死亡登记处的定期记录联系，被动地跟踪队列的死亡和癌症发生情况。队列中观察到的癌症发病率和死亡人数与基于新加坡所有华人的年龄性别特定发病率的相应预期数字相当。 我们将继续利用这一队列来检查潜在的癌症保护性饮食因素，这些因素在经过充分研究的西方人群中很少消费。我们未来5年的具体目标是：(1)评估茶的摄入量在癌症预防中的作用，同时考虑喝茶的类型(绿茶和红茶)以及个体易感因素，包括控制茶多酚的三个主要排泄途径(O-甲基化、葡萄糖醛酸化、硫酸盐化)的关键多态基因；以及(2)评估参与DNA损伤修复和细胞周期调控的基因在改变茶以及其他已确定的饮食保护因素与癌症之间的联系方面的潜在作用。

DESCRIPTION (provided by applicant): 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.