Difference in Prostate Cancer Rates between the United States and
Spain: Effect of Vitamin D
by
Kathryn Marvel
A PROJECT
submitted to
Oregon State University
University Honors College
and
International Degree Office
in partial fulfillment of
the requirements for the
degree of
Honors Baccalaureate of Science in Biochemistry/Biophysics (Honors Scholar)
and
Honors Baccalaureate of Arts of International Studies in Biochemistry/Biophysics
Presented May 30, 2006
Commencement June 2006
AN ABSTRACT OF THE THESIS OF
Kathryn Marvel for the degree of Honors Baccalaureate of Science in
Biochemistry/Biophysics and Honors Baccalaureate of Arts of International Studies in
Biochemistry/Biophysics presented on May 30, 2006. Title: Difference in Prostate
Cancer Rates Between the United States and Spain: Effect of Vitamin D
Abstract approved: ______________________________
Emily Ho
Prostate cancer is the most commonly diagnosed cancer in men, but rates around the
world vary greatly. Americans have the highest incidence rates in the world, 4 to 5 times
those of Spain. The hypothesis of this thesis was that vitamin D metabolism is a factor in
prostate cancer development and the aim was to examine differences in factors that
modulate vitamin D metabolism between the US and Spain, specifically sunlight
exposure and vitamin D receptor (VDR) polymorphisms. Through a search of papers that
examined sunlight exposure and prevalence of VDR polymorphisms, we found that Spain
had more ultraviolet exposure than the United States, but there was little difference in
proportions of VDR polymorphisms between the two populations. TaqI, BsmI, and FokI
polymorphisms of the VDR were studied. Proportions of TaqI and FokI were found to be
equivalent between the two populations. The rates of BsmI polymorphisms were found to
be statistically different, but the United States, not Spain, has higher proportions of the
protective allele. With no apparent rate differences in the VDR polymorphisms these do
not help explain the different prostate cancer rates. However, the increased sun exposure
in Spain may allow more vitamin D production which could be a contributing factor for
Spain having lower prostate cancer incidence rates.
Key Words: prostate cancer, vitamin D receptor, ultraviolet exposure
Corresponding e-mail address: marvelk@onid.orst.edu
©Copyright by Kathryn Marvel
May 30, 2006
All Rights Reserved
Difference in Prostate Cancer Rates between the United States and
Spain: Effect of Vitamin D
by
Kathryn Marvel
A PROJECT
submitted to
Oregon State University
University Honors College
and
International Degree Office
in partial fulfillment of
the requirements for the
degree of
Honors Baccalaureate of Science in Biochemistry/Biophysics (Honors Scholar)
and
Honors Baccalaureate of Arts of International Studies in Biochemistry/Biophysics
Presented May 30, 2006
Commencement June 2006
Honors Baccalaureate of Science in Biochemistry/Biophysics and Honors Baccalaureate
of Arts of International Studies in Biochemistry/Biophysics project of Kathryn Lynn
Marvel presented on May 30, 2006.
APPROVED:
_____________________________________________________
Mentor, representing Nutrition and Exercise Science
_____________________________________________________
Committee Member, representing Biochemistry/Biophysics
_____________________________________________________
Committee Member, representing Biochemistry/Biophysics
_____________________________________________________
Chair, Department of Biochemistry/Biophysics
_____________________________________________________
Director, International Degree Program
_____________________________________________________
Dean, University Honors College
I understand that my project will become part of the permanent collection of Oregon
State University, University Honors College. My signature below authorizes release of
my project to any reader upon request.
_____________________________________________________
Kathryn Lynn Marvel, Author
Table of Contents
Page
1. Introduction and Hypothesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
2. Background and Literature Review. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
a. Prostate function and prostate function. . . . . . . . . . . . . . . . . . . . . . . . . . 4
b. Prostate cancer risk factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
c. Vitamin D function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
d. Vitamin D metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
e. Vitamin D deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
f. Vitamin D and prostate cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
g. Sunlight exposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17
h. Vitamin D receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3. Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
a. Sunlight and ultraviolet exposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26
b. Vitamin D receptor polymorphisms. . . . . . . . . . . . . . . . . . . . . . . . . . . .30
i. TaqI Polymorphisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
ii. BsmI polymorphisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
iii. FokI polymorphisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4. Conclusions and Recommendations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38
5. Bibliography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42
List of Figures
Figure
Page
Figure 1: Structure of vitamin D3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8
Figure 2: Electromagnetic spectrum: the wavelength of various types of light. . . . .10
Figure 3: Conversion of 25OH to its two main metabolites. . . . . . . . . . . . . . . . . . .11
Figure 4: : Example of how 1,25OH Vitamin D (Calcitriol) acts to change gene
transcription and protein synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . .22
List of Tables
Table
Page
Table 1: Average Ultraviolet Index for seven American
cities between 1999 and 2003 . . . . . . . . . . . . . . . . . . . . . . . . . . . .27
Table 2: Ultraviolet Index for various Spanish cities between 2001-2002 . . . . . . 28
Table 3: Proportion of TaqI polymorphisms in the United States . . . . . . . . . . . . 32
Table 4: Proportion of TaqI polymorphisms in Spain . . . . . . . . . . . . . . . . . . . . . .32
Table 5: Proportion of BsmI polymorphisms in the United States. . . . . . . . . . . . .34
Table 6: Proportion of BsmI polymorphisms in Spain. . . . . . . . . . . . . . . . . . . . . .35
Table 7: Proportion of FokI polymorphisms in the United States. . . . . . . . . . . . . 36
Table 8: Proportion of FokI polymorphisms in the Spain . . . . . . . . . . . . . . . . . . . 37