MERIT Award Recipient: Laurence Kolonel, M.D., Ph.D.
Multiethnic Cohort Study of Diet and Cancer
Despite a growing body of evidence that a major fraction of cancer incidence is attributable to diet and the related factors of obesity and physical activity, few specific relationships are established. Earlier research by the Kolonel Laboratory on migrant Japanese showed that the risk of developing common cancers is largely determined by environmental factors (including diet and other lifestyle factors) rather than by the inheritance of rare, highly penetrant genes. On the other hand, certain striking discrepancies in the findings (such as lung cancer rates that were higher than expected among Native Hawaiians and lower than expected among Japanese) suggested an interaction between multiple exposures or between exposures and inherited characteristics. Such characteristics could include relatively common, low penetrant genetic variants involved in the metabolism of exogenous or endogenous substances, such as chemical constituents in foods or circulating hormones.
The goal of the research supported by this grant is to advance knowledge in this complex area by examining the effects of dietary variables and genetic make-up in a multiethnic population that provides a wider range of exposures than is usually available in nutritional epidemiologic studies. The study population is a cohort of 215,000 men and women representing five different ethnic groups (whites, African Americans, Japanese Americans, Latinos and Native Hawaiians) who enrolled in 1993-1996 by filling out a detailed questionnaire. The questionnaire obtained considerable detail about diet, as well as information on ethnic background, use of medications, past medical conditions, physical activity, solar exposure, smoking, and, in women, reproductive history and use of hormones. By means of careful surveillance on these participants (entailing personal contact, as well as linkage to population-based tumor registries in Hawaii and California), the Kolonel Laboratory is identifying all incident cases of cancer and will test a variety of etiologic hypotheses related to diet and cancer (such as increased risk of prostate cancer due to particular fatty acids found in animal products; decreased risk of lung cancer from flavonoids contained in certain fruits and vegetables; lower risk of selected cancers from moderate levels of regular physical activity, independent of obesity).
The Kolonel Laboratory is also collecting blood and urine samples, so that they will be able to examine genetic variants and biochemical markers of dietary exposures in the cohort participants. By exploring gene-environment interactions, the Kolonel Laboratory hopes to identify the basis for differences among individuals and among ethnic groups in their risks for developing cancer. For example, they will determine the effect on colorectal cancer risk of variant forms of genes such as some that are responsible for metabolizing the heterocyclic amines and polycyclic hydrocarbons that form in well-done meats. Such studies should help to clarify relationships that have been elusive until now. Since diet is a modifiable risk factor, the results of these studies, if confirmed by others, could lead to public health programs for primary prevention of cancer, and, ultimately, to a reduction in the cancer burden in the U.S. and elsewhere.