Associations between Vitamin D Receptor (VDR) Gene Polymorphisms and Colorectal Cancer Risk and Effect Modifications of Dietary Calcium and Vitamin D in a Japanese Population

Nobuyuki Takeshige,Takashi Ueki,Masao Tanaka,Yohichi Yasunami,Guang Yin,Takafumi Maekawa,Keizo Ohnaka,Hitoshi Ichimiya,Suminori Kono,Reiji Terasaka,Yoshihiko Maehara,Koji Ikejiri,Takeshi Okamura,Kenji Takenaka

doi:10.7314/apjcp.2015.16.5.2019

Abstract

Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a study of 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI, BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calcium and vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to be associated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio of colorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidence interval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreased risk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with high calcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk of colon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphisms were unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin D intake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer in Japanese, dependent on dietary calcium intake.

Highlights

Colorectal cancer is the third most common cancer in the world, with more than one million cases occurring every year (Ferlay et al, 2010)
In a study of 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI, BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calcium and vitamin D
The FokI polymorphism seemed to be associated with a decreased risk of colon cancer among those with high vitamin D intake

Summary

Introduction

Colorectal cancer is the third most common cancer in the world, with more than one million cases occurring every year (Ferlay et al, 2010). In Japan, the incidence rates of colorectal cancer rapidly increased until 1990s and have remained at the world highest levels (Kono 2004; Ferlay et al, 2010). Less convincing is the protective role of calcium intake as well as of dietary fiber. A possible protective role of vitamin D was noted as early as three decades ago (Garland et al, 1985), and supportive evidence has accumulated in the past decades (Gorham et al, 2007; Touvier et al, 2011). Much attention has recently been drawn to potential associations of the VDR gene polymorphisms with colorectal cancer risk (Raimondi et al, 2009; Touvier et al, 2011; Bai et al, 2012; Nassiri et al, 2013)

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