||5R03CA080662-02 Interpret this number
||University Of Southern California
||Tobacco Metabolism Genes and Gastric Cancer
In a recently completed case-control study of gastric cancer funded by
the California Tobacco-Related Disease Research Program 3RT-0122), we
have collected extensive questionnaire data on lifestyle factors from
over 600 gastric cancers patients and an equal number of population
controls. Our results showed that active smoking significantly
increased the risk of gastric cancer, consistent with the conclusion of
several recent reviews on smoking and gastric cancer development.
However, the precise mechanism by which tobacco smoke induces gastric
cancer in humans is still unclear. There is increasing evidence that
genetic polymorphisms in enzyme systems including cytochrome P450 CYP1A1
(CYP1A1), myloperoxidase (MPO) and glutathione S-transferases (GSTs) are
involved in the metabolism of tobacco carcinogens and influence the
risks of lung and bladder cancers. We hypothesize that these
polymorphic genes also play a role in determining a smokers' risk of
To investigate the roles of a series of tobacco-carcinogen-metabolizing
genes in influencing gastric cancer risk, we will use materials and
information collected from our case-control study on gastric cancer
(3RT-0122). Buffy coats were collected from 350 gastric cancer cases
and 450 age-, sex- and race-matched population controls. We are seeking
support to process these buffy coats and DNA extraction and subsequent
genotyping assays on extracted DNA. Specifically, we will test the
hypotheses that the risk of gastric cancer is increased among
individuals who: a) possess the GSTM1 null, the GSTT1 null and/or the
GSTP1 GG genotypes; and b) carry mutant CYP1A1 alleles. We will also
test the hypothesis that risk of gastric cancer is decreased among
individuals homozygous for the mutant AA allele of the MPO gene. We will
determine the independent effects of these genetic loci and their
interactive effects, if any, on gastric cancer development. In
addition, we will investigate if the level of smoking exposure modifies
any of these gene-disease relationships.
A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders.
, Yang D.
, Pike M.C.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2000 Oct; 9(10), p. 1051-8.