Page 87 - Vitamin D and Cancer

74 E. Giovannucci

Abbreviations

Ca Calcium
CI Confidence interval
D2 Ergocalciferol
D3 Cholecalciferol
1,25(OH) D 1,25-Dihydroxyvitamin D
2
25(OH)D 25-Hydroxyvitamin D
IU International unit
nmol/L Nanomoles per liter
ng/mL Nanograms per milliliter
NHL Non-Hodgkin lymphoma
RCT Randomized controlled trial
RR Relative risk
UV-B Ultraviolet B light

4.1 Introduction

The hypothesis that vitamin D confers protection against some cancers was first
based on some epidemiologic observations. As early as 1937, Peller and
Stephenson hypothesized that sunlight exposure, by inducing skin cancer, could
induce some degree of immunity against some internal cancers [1]. Then in 1941,
Apperly demonstrated an association between latitude and cancer mortality, lead-
ing him to hypothesize a direct benefit of sunlight on cancer mortality independent
of any effect on skin cancer [2]. These observations and hypotheses went largely
ignored until the early 1980s when Garland and Garland hypothesized that inad-
equate vitamin D status resulting from lower solar UV-B radiation exposure
accounted for the association between higher latitudes and increased mortality of
colon cancer [3], breast cancer [4], and ovarian cancer [5]. Thereafter, this pro-
posed anticarcinogenic effect of vitamin D was extended to prostate cancer [6, 7]
and to other malignancies [8].
These initial observations formed the basis of the vitamin D cancer hypothesis.
In the past several decades, laboratory studies have discovered numerous anticar-
cinogenic properties of vitamin D, including inducing differentiation and inhibit-
ing proliferation, invasiveness, angiogenesis, and metastatic potential. Over this
time, a variety of epidemiologic study designs have been utilized to assess expo-
sure to vitamin D at the individual level, and then to examine the estimated vita-
min D level to the risk of a specific cancer or to total cancer. This chapter will
review the epidemiologic evidence from cohort and case–control studies of the
association between vitamin D status and cancer risk, including studies directly
measuring circulating levels of 25(OH)vitamin D (25(OH)D), the presumed rele-
vant metabolite of vitamin D status, and surrogates or determinants of 25(OH)D