Vitamin D-Related Genetic Variants, Interactions with Vitamin D Exposure, and Breast Cancer Risk among Caucasian Women in Ontario

Abstract

Background: Vitamin D, from diet and sunlight exposure, may be associated with reduced breast-cancer risk. This study investigated if candidate gene variants in vitamin D pathways are associated with breast cancer risk, or modify the associations between breast cancer and vitamin D exposure.Methods: Breast cancer cases aged 25 to 74 years were identified from the Ontario Cancer Registry (histopathologically confirmed and diagnosed [2002][2003] and population-based controls were identified through random digit dialing of Ontario households. Saliva (DNA) was available for 1,777 cases and 1,839 controls. Multivariate logistic regression was used to evaluate associations between 19 single nucleotide polymorphisms (SNP) in vitamin D related genes, including vitamin D binding protein (GC), vitamin D receptor (VDR), and cytochrome P450 type 24A1 (CYP24A1). Statistical interactions were assessed using the likelihood ratio test.Results: Some SNPs were found to be significantly associated with breast cancer risk. For example, breast cancer risk was associated with the GC rs7041 TT genotype (age-adjusted odds ratio (OR) ¼ 1.23; 95% CI: 1.01, 1.51) and inversely with the VDR Fok1 (rs2228570) ff genotype (OR ¼ 0.71; 95% CI: 0.57, 0.88). Few significant gene-environment interactions were observed between dietary vitamin D and genetic variants.Conclusion: Our study suggests certain vitamin D related genetic variants may influence breast-cancer risk and we found limited evidence that genetic variants modify the associations between vitamin D exposure and breast cancer risk.Impact: Variation in vitamin D-related genotypes may help to explain inconsistent results from previous epidemiologic studies and may lead to targeted prevention strategies. Cancer Epidemiol Biomarkers Prev; 20(8); 1708-17. '2011 AACR.

Single Nucleotide Polymorphisms in the Gc Gene for Vitamin D Binding Protein in Common Cancers in Thailand

“…A significant association between the T allele in rs7041 and breast cancer has been reported in Caucasian women in Canada (Anderson et al, 2011). To our knowledge, our current study reports a significant association between rs7041 and lung cancer for the first time.…”

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

“…This protein has been noted as having a protective effect in breast cancer by facilitating transport of vitamin D metabolites (13) and has been shown to be downregulated in the serum of breast cancer patients (26). Some studies suggest that specific genetic variants of VDBP influence a woman's risk of developing breast cancer (27). In the aggregate, our results show an increase in plasma levels of VDBP in rats fed a high n-3:n-6 fatty acid ratio which provides support for an additional possible mechanism of chemoprevention by n-3 fatty acids.…”

Association Between VDR Polymorphisms and Breast Cancer: An Updated and Comparative Meta-analysis of Crude and Adjusted Odd Ratios

“…Case-control studies on Fok1 in breast cancer showed some evidence of increased risk among ff carriers (Sinotte et al, 2008;Gapska et al, 2009;McKay et al, 2009), which was confirmed by some later metaanalysis Tang et al, 2009;. However, these studies also reported some decreased risk among ff carriers (Anderson et al, 2011), or no association with breast cancer (Curran et al, 1999;Guy et al, 2004;John et al, 2007;Abbas et al, 2008;Engel et al, 2012;Rollison et al, 2012;Fuhrman et al, 2013;Mishra et al, 2013;Shahbazi et al, 2013). Similarly, mixed results have been observed concerning the relationship between other polymorphisms and the risk of breast cancer development.…”

“…2013; Shahbazi et al, 2013) but not in others (Buyru et al, 2003;Hefler et al, 2004;VandeVord et al, 2006;Trabert et al, 2007;Sinotte et al, 2008;Gapska et al, 2009;McKay et al, 2009;Anderson et al, 2011;Rollison et al, 2012;Mishra et al, 2013); Apa1 was found with positive relationship in some breast cancer studies (Curran et al, 1999;Sillanpaa et al, 2004;Dalessandri et al, 2012), but negative in others (Cui et al, 2001;Hou et al, 2002;Chakraborty et al, 2009;Anderson et al, 2011;Engel et al, 2012;Mishra et al, 2013); the same as Taq1, with associations in some studies (Cui et al, 2001;, but not in others (Curran et al, 1999;Dunning et al, 1999;Lundin et al, 1999;Hou et al, 2002;Newcomb et al, 2002;Buyru et al, 2003;Sillanpaa et al, 2004;John et al, 2007;Abbas et al, 2008;Chakraborty et al, 2009;Gapska et al, 2009;Anderson et al, 2011;Engel et al, 2012;Mishra et al, 2013); Cdx2, positive in some studies (Anderson et al, 2011;Yao et al, 2012; but not in others (Abbas et al, 2008;Zhou et ...…”