||5R01CA077973-03 Interpret this number
||Er Gene Polymorphisms and Breast and Endometrial Cancer
Our objective is to test, in an ethnically homogenous population, the
hypothesis that individual variation in the sensitivity to estrogens-
caused by polymorphism in the estrogen receptor (ER) gene-affects a
woman's risk of breast and endometrial cancer. Several polymorphisms
in the ER gene have recently been described, but no study has
adequately assessed their significance for malignant transformation.
Our approach is uniquely cost-effective since it builds on two recently
completed, coordinated, nationwide, population-based case-control
studies of breast and endometrial cancer in Sweden (funded by NIH and
American Cancer Society, respectively) encompassing women aged 50-74
with newly diagnosed breast cancer (n=3,900), endometrial cancer
(n=l,000), and controls (n=3,500). Detailed information on reproductive
factors and use of exogenous hormones allows the study proposed here
to focus on never-users and long-term users. We will randomly select
900 breast cancer cases, 900 endometrial cancer cases, and 1,034
Controls (expecting 900 with a uterus). For analyses within categories
of menopausal hormone use, this sample will be enriched with additional
controls and cancer cases who were long-term users of menopausal
hormones, for a total sample of 3,394 subjects. DNA for genetic
analysis will be obtained in the cases from non-malignant cells in the
tissue specimens, and among the controls from leucocytes in blood
samples. The genetic analyses will assess polymorphisms in Xba I and
Pvu II restriction sites in intron 1, a dinucleotide repeat
polymorphism upstream Of the gene, and two polymorphisms in exons 3 and
4. The overall associations of these genetic variants on the risk of
breast and endometrial cancer will be assessed in the random sample,
with careful control for exogenous hormone use and breast cancer risk
factors. Additional analyses within strata of menopausal hormone use
and other risk factors will be conducted to explore differences in the
effect of the polymorphisms. The study population will be large enough
to ensure detection of relative risks under 2.0 in most of the overall
analyses, and for most analyses among never-users of menopausal
Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.
, Lovmar L.
, Humphreys K.
, Magnusson C.
, Melhus H.
, Syvänen A.C.
, Kindmark A.
, Landegren U.
, Fermér M.L.
, Stiger F.
, et al.
Breast cancer research : BCR, 2004; 6(4), p. R437-49.