||5R01CA095790-04 Interpret this number
||Fred Hutchinson Cancer Research Center
||Persistent Organochlorines and Testicular Cancer Risk
The incidence of testicular germ cell carcinoma (TGCC), the most common
malignancy developing in young men, has increased several-fold since the 1950s.
Experimental and observational studies in animal systems have raised concern
that the increasing rates are due in part to population-wide, persistent
exposure to endocrine disrupting compounds from industrial and agricultural
applications. Whether human exposure to such chemicals is associated with TGCC
risk has not been directly studied. We propose to determine whether the risk of
TGCC is related to serum levels of persistent organochlorines, focusing on
p,p'-DDE, polychlorinated biphenyls (PCBs), and other compounds (e.g.,
dieldrin, hexachlorocyclohexanes, hexachlorobenzene). We also will examine
whether the risk of TGCC associated with these compounds is modified by genetic
susceptibility to mechanisms through which these compounds may alter TGCC risk.
For example, we will determine whether TGCC risk is related to interactions
between 1) elevated serum p,p'-DDE and polyglutamine repeat tract polymorphisms
in the androgen receptor (AR) gene, and 2) elevated serum PCB levels and
polymorphisms in oxidative stress defense enzyme genes.
To address these aims, we will conduct an ancillary investigation to the Male
Androgen Research Study (MARS), a recently-initiated, NCI-funded,
population-based case-control study of molecular genetic risk factors for TGCC.
MARS funding includes standard population-based case and control ascertainment
and recruitment, a detailed in-person interview, blood draw, and molecular
genetic analyses of polymorphisms in androgen synthesis, metabolism, and
signaling genes (including AR). The ancillary study will include approximately
250 cases of TGCC and 750 controls recruited as part of MARS. Funding for the
ancillary study will provide for 1) a rapid case ascertainment and recruitment
system to minimize effects of chemotherapy on serum measures of organochlorine
residues among TGCC patients; 2) assay of organochlorine pesticides and PCBs by
high resolution gas chromatography/isotope dilution high resolution mass
spectometry; and 3) assays for common polymorphisms in genes involved in
oxidative stress defense systems (manganese superoxide dismutase, glutathione
S-transferases M1, M3, T1, and P1). There will be adequate statistical power to
detect relatively weak overall associations, as well as less than 3-fold
interaction effects. The results should add significant new information to our
understanding of the role of environmental contaminants to the pathogenesis of
Serum organochlorine pesticide residues and risk of testicular germ cell carcinoma: a population-based case-control study.
, Davis M.D.
, Eaton D.L.
, Weiss N.S.
, Barr D.B.
, Doody D.R.
, Fish S.
, Needham L.L.
, Chen C.
, Schwartz S.M.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Aug; 17(8), p. 2012-8.