Vitamin D Receptor Gene and Breast Cancer Risk

Institution: University of Southern California
Investigator(s): Sue Ann  Ingles , DrPH -
Award Cycle: 1997 (Cycle III) Grant #: 3IB-0089 Award: $241,803
Award Type: IDEA
Research Priorities
Etiology>Environment and gene/environment interactions: nature vs. nurture



Initial Award Abstract (1997)
Previous evidence suggests that vitamin D, by interacting with vitamin D receptors in the breast and other tissues, prevents cancer. The vitamin D receptor (VDR) plays a key role in this process, and occurs in at least two different genetic types. Individuals who inherit the "weak" type of VDR gene from both parents may be at increased risk of breast cancer. Treatment with vitamin D or modified forms of vitamin D might be useful for prevention of breast cancer or its progression in these individuals.

We plan to study several VDR genetic markers as well as blood vitamin D levels in women with and without breast cancer. This information may help us to understand how "weak" VDR genes influence cancer risk and may help us create better tests for the "weak" VDR gene. If we are able to demonstrate that "weak" VDR genes are associated with breast cancer risk, we may be able to identify susceptible individuals who are candidates for prevention studies. Improvement of vitamin D status may have an especially large impact in the African-American population, which is known to be more susceptible to vitamin D deficiency due to less efficient production of vitamin D precursors by sunlight in darker skinned individuals. Because the high-risk form of the VDR gene is relatively common in all ethnic groups, this work could lead to a significant reduction in the economic and human cost of breast cancer in California.


Final Report (1999)
Previous evidence suggests that vitamin D may prevent cancer by interacting with vitamin D receptors in the breast and other tissues. The vitamin D receptor (VDR) plays a key role in this process and occurs in at least two different genetic "types". The overall goal of this study was to develop genetic "markers" that can be used to measure VDR types, and to determine whether women with specific VDR types are relatively protected against breast cancer.

Our first specific aim involved measuring two different VDR markers for 1000 women (500 African-Americans and 500 Latinas), some of whom have breast cancer and some of whom do not. Our second airy involved measuring blood vitamin D levels from some of these same women. We found that among Latina women, one specific VDR type conferred protection against breast cancer. Women who inherited the protective type of VDR gene from both parents had approximately one-third the risk of breast cancer compared to women who inherited two of the "non-protective" VDR genes. Women who inherited one protective and one non-protective VDR gene were at intermediate risk. Blood levels of vitamin D were also higher in women who inherited two of the protective VDR genes compared to other women.

Although we were able to test for the protective-type VDR gene in Latinas, these genetic markers do not work well in the African-American population. To understand why this is so, we examined the VDR gene more closely and found a third VDR genetic type. Women who inherited this third VDR type from both parents appear to have the highest levels of vitamin D in the blood, however these results need to be confirmed in larger studies.

This study indicates that nearly a quarter of women in California may be at increased risk of breast cancer, either because they have inherited two copies of a non-protective-type VDR gene or because they have vitamin D deficiency. Development of effective interventions targeted to these at-risk women could significantly impact breast cancer incidence or mortality in California.
Vitamin D receptor genotype and breast cancer in Latinas (United States)
Periodical:Cancer Causes Control
Index Medicus: Cancer Causes Contol
Authors: Ingles SA, Garcia DG, Wang W, Nieters A, Henderson BE, Kolonel LN, Haile RW, Coetzee GA.
Yr: 2000 Vol: 11 Nbr: 1 Abs: Pg:25-30