Multi-ethnic Study of Genetic Control of Plasma Hormones

Institution: University of Southern California
Investigator(s): Heather Feigelson, Ph.D., M.P.H. -
Award Cycle: 1998 (Cycle IV) Grant #: 4KB-0147 Award: $141,639
Award Type: New Investigator Awards
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle



Initial Award Abstract (1998)
A large and compelling body of scientific evidence indicates that estrogens play a major role in causing breast cancer. We have been investigating three genes that are involved in the production of estrogens in the body and have found that one gene, called CYP17, is associated with a 2.5 times increased risk of advanced breast cancer. We have also found that CYP17 may, in part, be responsible for the genetic control of hormone levels occurring naturally in the body.

<>In this study, we propose to expand this work by examining the association between CYP17 and a second gene, HSD17B1, and plasma levels of several steroid hormones in healthy, postmenopausal women. We will also examine the relationships between these genes and important known risk factors for breast cancer including body weight, age at menarche, age at first birth, number of children the woman has borne, age at menopause, and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) among healthy postmenopausal women.

The study will include 170 randomly selected women from each of four racial-ethnic groups: African-American, Japanese, Latina and White, resulting in a total sample size of 680. These women are part of a larger on-going study of cancer.

This study could have several important consequences. In the field of cancer prevention, there is likely to be substantial interest in the interaction between these genes and exogenous estrogen use, i.e., OCs and HRT. As a genetic marker of risk, these genotypes may provide new tools for identifying high risk groups of women for prevention and treatment protocols. Finally, understanding the genetic control of steroid hormone biosynthesis can provide new insights into reproductive biology and endocrinology.


Final Report (1999)
Estrogens and other hormones play an important role in causing breast cancer. We have been investigating two genes that are involved in the synthesis of estrogens in the body. We previously showed that one of these genes, called CYP17, is associated with a 2.5 times increased risk for advanced breast cancer. We have also shown that in young, healthy women, CYP17 is associated with the levels of estrogen and progesterone in the body.

The purpose of this study was to expand our earlier work by examining the association between CYP17 and a second gene, called HSD17B1, and plasma levels of steroid hormones in healthy, postmenopausal women. We also wanted to determine if these genes influenced other important risk factors for breast cancer including body weight, use of hormone replacement therapy (HRT), age at menarche and age at first birth.

This grant was terminated early (September 1, 1999) after 14 months of funding due to a change in the PI status. However, we accomplished a great deal in this short time. We provided preliminary evidence that both CYP17 and HSD17B1 influence the levels of hormones in the body. Although these findings do not reach statistical significance, on average, levels of androstenedione and estrone are 5-9% higher in women who carry the "higher risk" type of either of these two genes. The results for estradiol were less consistent.

We also provided the first evidence that CYP17 influences a modifiable breast cancer risk factor. We showed that depending on CYP17 genotype, some women were twice as likely to be current users of HRT. These findings were recently published and suggest that CYP 17 genotype may provide an important piece of information for women seeking advice on HRT use, and that the actual risk of breast cancer associated with HRT use may be higher than previously reported. These results were consistent across all four ethnic groups (African-American, Japanese, Latina and White) included in our study.

Cytochrome P450c17alpha gene (CYP17) polymorphism predicts use of hormone replacement therapy
Periodical:Cancer Research
Index Medicus: Cancer Res
Authors: Feigelson HS, McKean-Cowdin R, Pike MC, Coetzee GA, Kolonel LN, Nomura AM, et al.
Yr: 1999 Vol: 59 Nbr: 16 Abs: Pg:3908-10

A polymorphism in CYP17 gene increases the risk of breast cancer
Periodical:Cancer Research
Index Medicus: Cancer Res
Authors: Feigelson HS, Coetzee GA, Kolonel LN, Ross RK, Henderson BE
Yr: 1997 Vol: 57 Nbr: 6 Abs: Pg:1063-5