An epidemiologic study of mammographic density measures and common polymorphisms in genes of lipoproteins metabolism and the growth hormone-insulin like growth factor I axis.
Published: 2005
Language: eng
Number of pages: 217
Description: Both polymorphism of GH1 were associated with percent density and non-dense area in all women, and had borderline association with these traits in the menopausal subgroups. Homozygous GH1 -57T and GH1 -75A subjects had less non-dense area and greater percent density. GH1 -75AA subjects had significantly greater serum GH.A cross-sectional study was used to identify common polymorphisms associated with mammography density, a strong and heritable risk factor for breast cancer. These polymorphisms were tested for association with other breast cancer risk factors, including anthropometric measures, serum lipoproteins, sex hormones, growth hormones and factors, and markers of oxidative stress. The polymorphisms selected were paraoxonase 1 (PON1) Q192R; apolipoprotein E (APOE) isoforms; low-density lipoprotein receptor ( LDLR) exon 12 C>T (detectable with Hinc II), pituitary growth hormone (GH1) -57 G>T and -75 G>A; and growth hormone releasing hormone receptor (GHRHR) A57T.Participants were recruited from mammography units in three Toronto hospitals. Blood was collected at home visits to measure biochemical traits and to extract DNA. Epidemiologic information and anthropometric measures were obtained by a trained interviewer. Genotypes were determined by PCR-based methods. Mammograms were digitized and measured using a computer-based method. Associations were assessed using analysis of covariance, results are reported adjusted for age, body mass index (BMI), ethnicity, and menopausal status.These findings suggest that mammographic measures are determined in part by common genetic polymorphisms that influence lipid metabolism and GH-IGF1 axis. These polymorphisms are also associated with breast cancer risk factors including anthropometric measures, serum malondialdehyde, and insulin.APOE isoform genotype was significantly associated with total breast area in all women, and had a borderline association among pre- and postmenopausal women. Subjects who had at least one copy of the  APOE E2 allele had lower total breast area, lower serum insulin, greater growth hormone, and lower serum TC, LDL-C and apo B.Postmenopausal PON1 R192 carriers had significantly greater dense area and lower serum malondialdehyde (MDA), a marker of oxidative stress. Among Caucasian postmenopausal women the PON1 R192 carriers also has lower progesterone, increased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B) than other subjects.
Notes: Thesis (Ph.D.)--University of Toronto, 2005.

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Source: Dissertation Abstracts International, Volume: 66-06, Section: B, page: 2965.