Major Areas of Emphasis - Genetic Epidemiology
Interdisciplinary Studies in the Genetic Epidemiology of Cancer
Gene-environment Interactions: The Odyssey Cohort
Kathy J. Helzlsouer, M.D., M.H.S.
Johns Hopkins School of Medicine
Baltimore, Md.
Polymorphisms of many genes controlling metabolism of xenobiotic compounds
and DNA repair processes are associated with susceptibility to cancer
as well as other chronic diseases. Studies are needed that are more holistic
in design and provide insights into the net effect on health of having
specific genotypes.
The researchers will conduct a population-based cohort study to examine
the broad impact of genetic variation in candidate genes and their interaction
with environmental exposures on cancer incidence and survival specifically,
and health and aging more generally. Participants (N=8395) of two blood
and data specimen banks CLUE I (1974) and CLUE II (1989) comprise the
study cohort (Odyssey Cohort). The cohort has been followed prospectively
for 24 years, and information on environmental factors such as smoking,
education, and housing are available as far back as 1963. DNA will be
extracted from buffy coat specimens obtained from participants in 1989
and stored at -70 C.
The researchers will investigate polymorphisms in genes coding for enzymes
that:
- metabolize nutrients and hormones (MTHFR, VDR, CYP17, CYP1B1, COMT,
CYP3A4);
- metabolize carcinogens (ADH, GSTM1, NAT1, ans NAT2, NOS, CYP1A1, CYP1B1,
EH); and
- control DNA repair processes (XRCC1, XRCC3, XPD).
In this cohort, power is greater than 90% to detect a relative risk of
2 for main effects of genotypes on mortality and cancer incidence, and
at least 80% to detect gene-environment and gene-gene interactions of
2-fold for the major cancer sites (such as breast, prostate, and colorectal)
and 3- to 5-fold for less common cancers (such as endometrial and bladder
cancer).
As additional polymorphisms in candidate genes with potential relevance
to the major health outcomes are identified, the researchers will be able
to investigate their impact on health and survival.
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