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The multiethnic cohort study: exploring genes, lifestyle and cancer risk

Key Points

  • Asian migrants to the United States have shown major changes in rates of several important cancers. An understanding of the reasons for these changing rates provides an important insight into cancer causation.

  • The Multiethnic Cohort (MEC) Study was established to use variations in specific rates of disease in different ethnic groups to characterize the environmental and genetic contributions to certain common cancers.

  • In the MEC, breast cancer rates are highest among native Hawaiians and Japanese. Differences in established breast cancer risk factors do not explain these high risks.

  • Prostate cancer rates are highest in African Americans. Because only age and family history are additional known risk factors for prostate cancer, systematic research is underway to identify cancer-associated variants in the androgen growth factor and in as yet unidentified gene families.

  • Variation in coding and regulatory regions of various genes contributes to susceptibility to many chronic diseases, such as cancer. Clarifying this variation using population-based protocols necessitates the careful characterization of each gene. For association studies, large and well-characterized populations of diseased and matched non-diseased individuals are crucial to minimize the limitations that have applied to many studies published so far.

  • Variation in disease-associated alleles by race and ethnic group is a key strength of the MEC and other such large population-based studies.

Abstract

The search for the causes of cancer and means of cancer prevention has entered a new era as recent developments allow correlation of environmental and behavioural exposures, genetic variation and patient outcomes. The Multiethnic Cohort Study was designed to take advantage of these advances to prospectively explore the roles of lifestyle and genetic susceptibility in the occurrence of cancer. The ethnic diversity of the cohort in this study provides a wide range of dietary exposures and genetic variation, thereby providing a unique dimension to this research.

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Figure 1: Cancer incidence in Japanese migrants to Hawaii.
Figure 2: Average annual (1994–1999) cancer incidence rates by racial/ethnic group in the MEC Study.
Figure 3: Main candidate contributors to breast cancer risk and selected genomic changes in breast epithelial cells.
Figure 4: The prostate cancer candidate genes in the androgen and growth-factor pathways.

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Author information

Authors and Affiliations

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Correspondence to Brian E. Henderson.

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Related links

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DATABASES

Cancer.gov

breast cancer

colorectal cancer

lung cancer

prostate cancer

Entrez Gene

BRCA1

BRCA2

CYP17

CYP19

ERBB2

HSD17B1

SRD5A2

TP53

FURTHER INFORMATION

International HapMap Project

Glossary

PROSTATE-SPECIFIC ANTIGEN

(PSA). A serine protease that is secreted by prostatic epithelial cells and found in the serum. As it is almost exclusively a product of prostate cells, measurement in blood has proved to be useful as a tumour marker for diagnosis of prostate cancer and monitoring the effectiveness of treatment.

LINKAGE DISEQUILIBRIUM

The preferential association of a particular allele — for example, a mutant allele for a disease — with a specific allele at a nearby locus more frequently than would be expected by chance.

PENETRANCE

The proportion of affected individuals among the carriers of a particular mutation. If most individuals with a mutated disease gene show the disease phenotype, then the disease is said to be 'highly penetrant'.

ADMIXTURE MAPPING

Mapping of the gene flow between differentiated populations.

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Kolonel, L., Altshuler, D. & Henderson, B. The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nat Rev Cancer 4, 519–527 (2004). https://doi.org/10.1038/nrc1389

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