This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le Marchand, L. Articles by Lyu, L.-C. Search for Related Content PubMed PubMed Citation Articles by Le Marchand, L. Articles by Lyu, L.-C.

Independent and Joint Effects of Family History and Lifestyle on Colorectal Cancer Risk: Implications for Prevention¹

Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813

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.

This article has been cited by other articles:

				L. Le Marchand The Predominance of the Environment over Genes in Cancer Causation: Implications for Genetic Epidemiology Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1037 - 1039. [Full Text] [PDF]

				E. Fernandez, S. Gallus, C. La Vecchia, R. Talamini, E. Negri, and S. Franceschi Family History and Environmental Risk Factors for Colon Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 658 - 661. [Abstract] [Full Text] [PDF]

				T. Otani, M. Iwasaki, S. Yamamoto, T. Sobue, T. Hanaoka, M. Inoue, and S. Tsugane Alcohol Consumption, Smoking, and Subsequent Risk of Colorectal Cancer in Middle-Aged and Elderly Japanese Men and Women: Japan Public Health Center-based Prospective Study Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1492 - 1500. [Abstract] [Full Text] [PDF]

				A. M. Easson, M. Cotterchio, J. A. Crosby, H. Sutherland, D. Dale, M. Aronson, E. Holowaty, and S. Gallinger A Population-Based Study of the Extent of Surgical Resection of Potentially Curable Colon Cancer Ann. Surg. Oncol., May 1, 2002; 9(4): 380 - 387. [Abstract] [Full Text] [PDF]

				C. S. Fuchs, W. C. Willett, G. A. Colditz, D. J. Hunter, M. J. Stampfer, F. E. Speizer, and E. L. Giovannucci The Influence of Folate and Multivitamin Use on the Familial Risk of Colon Cancer in Women Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 227 - 234. [Abstract] [Full Text] [PDF]

				L. Le Marchand, J. H. Hankin, L. R. Wilkens, L. M. Pierce, A. Franke, L. N. Kolonel, A. Seifried, L. J. Custer, W. Chang, A. Lum-Jones, et al. Combined Effects of Well-done Red Meat, Smoking, and Rapid N-Acetyltransferase 2 and CYP1A2 Phenotypes in Increasing Colorectal Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1259 - 1266. [Abstract] [Full Text] [PDF]

				L. L. Marchand Combined Influence of Genetic and Dietary Factors on Colorectal Cancer Incidence in Japanese Americans J Natl Cancer Inst Monographs, December 1, 1999; 1999(26): 101 - 105. [Abstract] [Full Text]

				F. P. Li and A. S. Whittemore Genetically Tailored Preventive Strategies: an Effective Plan for the Twenty-first Century? Cancer Epidemiol. Biomarkers Prev., August 1, 1999; 8(8): 649 - 658. [Abstract] [Full Text]