DESCRIPTION (provided by applicant): There is considerable epidemiologic
evidence that alcohol intake is related to risk of breast cancer and that
intake of vegetables and fruits may reduce risk. Utilizing an existing case
control study, we propose to examine two etiological mechanisms, one-carbon
metabolism and/or oxidative stress and breast cancer. Our first aim is to
examine the relation of elements related to one-carbon metabolism with risk. We
propose a) to investigate genetic variation in enzymes important in one-carbon
metabolism (methylene tetrahydrofolate reductase (MTHFR), methionine synthase
(MS) and cystathione B-synthase (CBS)) in relation to risk and to investigate
interaction of these genetic factors with dietary folate and alcohol with
breast cancer risk; b) to investigate the association of dietary folate and
alcohol and these genetic factors with total p53 mutations and with particular
p53 mutations and c) to investigate the association of dietary folate and
alcohol and these genetic factors with hypermethylation of the p16 gene, the
BRCA1 gene and the estrogen receptor gene in breast tumors. Our second aim is
to examine elements related to oxidative stress and antioxidants with risk. We
propose to a) examine the relation of genetic variation in an enzyme important
in the control of oxidative balance (manganese superoxide dismutase (MnSOD))
and to examine interactions of this genetic factor with dietary factors both
oxidants and antioxidants; and b) to investigate the association between
dietary sources of oxidants and antioxidants with total and particular p53
mutations. By combining information on intake, genetic susceptibility and tumor
characteristics, it will be possible to make clearer inferences about the role
of these two mechanisms in breast cancer etiology, with potentially important
public health implications.
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