GENE-HORMONE INTERACTION AND RISK OF BREAST CANCER
Z Mara
Wake Forest University Health Sciencescity: Winston-salem country: United States (us)
Grant 5R01CA149135-02 from National Cancer Institute
Abstract: Hormone Therapy (HT) is commonly used to relieve the symptoms associated with menopause. Recent studies show HT is associated with an increased risk of breast cancer and cardiovascular disease (CVD). However, some women may have differing degrees of susceptibility to these HT-related risks, based on genetic background. The overall hypothesis of this study is that common genetic variants can be used to classify women into low or neutral risk groups for developing breast cancer due to HT use (gene-hormone interaction). We specially hypothesize that 1) a subset of genetic variants account for individual differences in risk of developing breast cancer upon HT use (E+P or E only) on breast cancer risk, 2) those SNPs may or may not alter the risk of developing CVD upon HT use. We will identify the genetic variants using data and samples from the Hormone Therapy Trial (HT) of the Women´s Health Initiative (WHI) study, a large randomized, double-blind, placebo-controlled clinical trial, and perform a replication study in the WHI Observational Study (OS). To test these hypotheses, we have four specific aims. Aim 1 is to identify SNPs that account for individual differences in risk of developing breast cancer upon HT use (SNP-HT interactions). Aim 2 is to confirm the top significant SNPs identified in Aim 1 among women in the OS arm. Aim 3 is to evaluate the SNP-HT interaction with other phenotypes (primarily CVD) among women in the OS arm. Aim 4 is to estimate the individual absolute risk of developing breast cancer upon HT use among women in the OS arm. We expect to identify a subset of SNPs that alter the risk of developing breast cancer upon HT use Results from this study could benefit millions of women who suffer from menopausal symptoms. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and may potentially improve clinical decision making for HT use. Individual HT-breast cancer risk assessment is important for identifying women for whom the benefits may outweigh the risks versus those women in whom the risks outweigh the benefits. Hormone therapy (HT), the most commonly used approach to treat the symptoms associated with menopause, has been dropped because of the concerns of increased breast cancer and other health risk. Genetic variants which interact with hormone therapy can be used as markers to classify women into low or neutral risk groups for developing breast cancer with HT use. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and improve clinical decision making for HT use
Keywords: Accounting; Adverse effects; Affect; Age; arm; base; Benefits and Risks; Biological; Breast Cancer Risk Assessment Tool; cancer risk; Candidate Disease Gene; Cardiovascular Diseases; cardiovascular disorder prevention; Clinical; clinical decision-making; Confounding Factors (Epidemiology); Controlled Clinical Trials; Coronary heart disease; cost effective; Data; Disease; disease phenotype; Double-Blind Method; Drops; Estrogen Receptor Status; Estrogens; Exposure to; Genes; Genetic; Genetic Markers; genetic variant; genome wide association study; Genotype; Health; hormone therapy; Hormones; improved; Individual; Individual Differences; Logistic Regressions; malignant breast neoplasm; Menopausal Symptom; Menopause; Nested Case-Control Study; Observational Study; Outcome; Phenotype; Placebo Control; Placebos; Population Study; Postmenopause; Predisposition; Progestins; public health relevance; Quality of life; Race; Randomized; Randomized Clinical Trials; Regression Analysis; Research; Research Design; Risk; Risk Assessment; Risk Factors; Sampling; SNP genotyping; Staging; stroke; Symptoms; Testing; Time; United States; Vasomotor; Venous; Woman; Women`s Health
Relevance: Narrative Hormone therapy (HT), the most commonly used approach to treat the symptoms associated with menopause, has been dropped because of the concerns of increased breast cancer and other health risk. Genetic variants which interact with hormone therapy can be used as markers to classify women into low or neutral risk groups for developing breast cancer with HT use. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and improve clinical decision making for HT use
Project start date: 2011-03-01
Project end date: 2014-02-28
Budget start date: 1-MAR-2012
Budget end date: 28-FEB-2013
5R01CA149135-02 (2012): $598207
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Z Mara
GENE-HORMONE INTERACTION AND RISK OF BREAST CANCER
Z Mara
Wake Forest University Health Sciencescity: Winston-salem country: United States (us)
Grant 1R01CA149135-01A1 from National Cancer Institute
Abstract: Hormone Therapy (HT) is commonly used to relieve the symptoms associated with menopause. Recent studies show HT is associated with an increased risk of breast cancer and cardiovascular disease (CVD). However, some women may have differing degrees of susceptibility to these HT-related risks, based on genetic background. The overall hypothesis of this study is that common genetic variants can be used to classify women into low or neutral risk groups for developing breast cancer due to HT use (gene-hormone interaction). We specially hypothesize that 1) a subset of genetic variants account for individual differences in risk of developing breast cancer upon HT use (E+P or E only) on breast cancer risk, 2) those SNPs may or may not alter the risk of developing CVD upon HT use. We will identify the genetic variants using data and samples from the Hormone Therapy Trial (HT) of the Women´s Health Initiative (WHI) study, a large randomized, double-blind, placebo-controlled clinical trial, and perform a replication study in the WHI Observational Study (OS). To test these hypotheses, we have four specific aims. Aim 1 is to identify SNPs that account for individual differences in risk of developing breast cancer upon HT use (SNP-HT interactions). Aim 2 is to confirm the top significant SNPs identified in Aim 1 among women in the OS arm. Aim 3 is to evaluate the SNP-HT interaction with other phenotypes (primarily CVD) among women in the OS arm. Aim 4 is to estimate the individual absolute risk of developing breast cancer upon HT use among women in the OS arm. We expect to identify a subset of SNPs that alter the risk of developing breast cancer upon HT use Results from this study could benefit millions of women who suffer from menopausal symptoms. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and may potentially improve clinical decision making for HT use. Individual HT-breast cancer risk assessment is important for identifying women for whom the benefits may outweigh the risks versus those women in whom the risks outweigh the benefits. Hormone therapy (HT), the most commonly used approach to treat the symptoms associated with menopause, has been dropped because of the concerns of increased breast cancer and other health risk. Genetic variants which interact with hormone therapy can be used as markers to classify women into low or neutral risk groups for developing breast cancer with HT use. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and improve clinical decision making for HT use
Keywords: Accounting; Adverse effects; Affect; Age; Apoplexy; arm; base; Benefits and Risks; Biological; brain attack; Breast Cancer Gail Model; Breast Cancer Gail Model Risk Assessment Tool; Breast Cancer Risk Assessment Tool; Cancer of Breast; cancer risk; Candidate Disease Gene; Candidate Gene; cardiac disease prevention; cardiovascular disease prevention; Cardiovascular Diseases; cardiovascular disorder; cardiovascular disorder prevention; Cerebral Stroke; cerebral vascular accident; Cerebrovascular accident; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Change of Life, Female; Chemotherapy-Hormones/Steroids; Clinical; clinical decision-making; Confounding Factor, Epidemiologic; Confounding Factors (Epidemiology); Confounding Variables; Controlled Clinical Trials; Corlutina; Corluvite; Coronary Disease; coronary disorder; Coronary heart disease; cost effective; Cyclogest; Data; Disease; disease phenotype; disease/disorder; Disorder; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Drops; Endocrine Gland Secretion; Endocrine Therapy; ER Status; Estrogen Receptor Status; Estrogenic Agents; Estrogenic Compounds; Estrogens; Exposure to; Female Health; Gail model; Genes; Genetic; Genetic Markers; genetic variant; genome wide association scan; genome wide association studies; genome wide association study; genome-wide scan; genomewide association scan; genomewide association studies; genomewide association study; genomewide scan; Genotype; Gestagenic Agents; Gestagens; Gestiron; Gestone; GWAS; Health; Hormonal Therapy; hormone therapy; Hormones; improved; Individual; Individual Differences; Lipo-Lutin; Logistic Regressions; Luteohormone; Lutocyclin; Lutocylin M; Lutogyl; Lutromone; malignant breast neoplasm; Malignant neoplasm of breast; Malignant Tumor of the Breast; menopausal; Menopausal Symptom; Menopause; Nested Case-Control Study; Observational Study; Outcome; PBO; Phenotype; Placebo Control; Placebos; Population Study; post-menopausal; Post-menopausal Period; Post-Menopause; postmenopausal; Postmenopausal Period; Postmenopause; Predisposition; Progestagenic Agents; Progestasert; Progestational Agents; Progestational Compounds; Progestational Hormones; Progesterone Agents; Progestins; Progestogel; Progestogens; Progestol; Progeston; Prolidon; Proluton; public health relevance; QOL; Quality of life; Race; Racial Group; randomisation; randomization; Randomized; Randomized Clinical Trials; randomly assigned; Regression Analyses; Regression Analysis; Regression Diagnostics; Research; Research Design; Risk; Risk Assessment; Risk Factors; Sampling; sham therapy; Sham Treatment; side effect; SNP genotyping; Staging; Statistical Regression; Stocks, Racial; stroke; Stroke; study design; Study Type; Susceptibility; Symptoms; Syngesterone; Testing; Therapeutic Estrogen; Therapeutic Hormone; Therapeutic Progestin; therapy adverse effect; Time; treatment adverse effect; Treatment Side Effects; United States; Utrogestan; Vascular Accident, Brain; Vasomotor; Venous; whole genome association studies; whole genome association study; Woman; Women`s Health
Relevance: Narrative Hormone therapy (HT), the most commonly used approach to treat the symptoms associated with menopause, has been dropped because of the concerns of increased breast cancer and other health risk. Genetic variants which interact with hormone therapy can be used as markers to classify women into low or neutral risk groups for developing breast cancer with HT use. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and improve clinical decision making for HT use
Project start date: 2011-03-01
Project end date: 2014-02-28
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-10-067
1R01CA149135-01A1 (2011): $658280