Le Marchand L, Wilkens L R, Hankin J H, Kolonel L N, Lyu L C
Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
Cancer Epidemiol Biomarkers Prev. 1999 Jan;8(1):45-51.
It has been suggested that, for a substantial proportion of "sporadic" colorectal cancers (CRCs), inheritance determines individual susceptibility and that lifestyle determines which susceptible individuals express cancer. Because the genetic basis of this inherited susceptibility remains undefined, we used family history of the disease as a proxy for a genetic predisposition to examine its interactions with a variety of lifestyle factors in a large population-based case-control study of CRC. The subjects were 698 male and 494 female Japanese, Caucasian, Filipino, Hawaiian, and Chinese patients diagnosed with CRC in Hawaii during 1987-1991 and 1192 population controls matched to cases on age, sex, and ethnicity. Fourteen percent of the cases and 6% of the controls reported a family history of CRC among parents or siblings. After adjusting for other covariates, significant interactions with family history were found for beef and ethanol intakes in males (P = 0.03). Relative to men without a family history and whose intake fell in the lower third, odds ratios (ORs) for CRC for men with a family history and in the upper tertile of intake were 10.8 [95% confidence interval (CI), 4.2-27.6] and 7.5 (CI, 3.1-18.2) for beef and ethanol, respectively. The corresponding ORs for men without a family history and in the upper tertile were 1.5 (CI, 1.0-2.3) and 1.4 (CI, 1.0-1.9), respectively. No interactions were detected in women. Using a summary measure of lifestyle, we found that family history was not associated with CRC among men who were at the lower-risk tertile for all of the lifestyle risk factors. In contrast, the OR for men with a family history and at the higher-risk tertile for all of the lifestyle variables was 11.7 (CI, 5.8-23.9). In the absence of a family history, this OR was 4.8 (CI, 3.2-7.2). These data suggest that family history increases the risk of sporadic CRC in men mainly through its interaction with lifestyle exposures, primarily a high beef and ethanol intake, and are consistent with recent reports of effect modifications of dietary associations by metabolic genes. Computation of population attributable risks also suggested that a comprehensive reduction in exposure to lifestyle risk factors--and more specifically to ethanol and beef for individuals with a familial predisposition for the disease--may have a large beneficial effect on CRC incidence.
有人提出，对于相当一部分“散发性”结直肠癌（CRC）而言，遗传决定个体易感性，而生活方式决定哪些易感个体患癌。由于这种遗传易感性的基因基础尚不清楚，我们在一项基于人群的大型CRC病例对照研究中，以疾病家族史作为遗传易感性的替代指标，来研究其与多种生活方式因素的相互作用。研究对象为1987年至1991年期间在夏威夷被诊断为CRC的698名男性和494名女性日本、高加索、菲律宾、夏威夷和中国患者，以及1192名在年龄、性别和种族上与病例匹配的人群对照。14%的病例和6%的对照报告其父母或兄弟姐妹中有CRC家族史。在对其他协变量进行调整后，发现男性中牛肉和乙醇摄入量与家族史存在显著相互作用（P = 0.03）。相对于无家族史且摄入量处于下三分之一的男性，有家族史且摄入量处于上三分位的男性患CRC的优势比（OR），牛肉为10.8 [95%置信区间（CI），4.2 - 27.6]，乙醇为7.5（CI，3.1 - 18.2）。无家族史且摄入量处于上三分位的男性相应OR分别为1.5（CI，1.0 - 2.3）和1.4（CI，1.0 - 1.9）。女性中未检测到相互作用。使用生活方式的综合衡量指标，我们发现对于所有生活方式风险因素处于低风险三分位的男性，家族史与CRC无关。相比之下，对于所有生活方式变量处于高风险三分位且有家族史的男性，OR为11.7（CI，5.8 - 23.9）。在无家族史的情况下，该OR为4.8（CI，3.2 - 7.2）。这些数据表明家族史主要通过与生活方式暴露（主要是高牛肉和乙醇摄入量）的相互作用增加男性散发性CRC的风险，这与近期关于代谢基因对饮食关联的效应修正的报道一致。人群归因风险的计算还表明，全面减少生活方式风险因素的暴露——更具体地说，对于有家族性疾病易感性的个体减少乙醇和牛肉的暴露——可能对CRC发病率产生很大的有益影响。
