The<i>Gc2</i>Allele of the Vitamin D Binding Protein Is Associated with a Decreased Postmenopausal Breast Cancer Risk, Independent of the Vitamin D Status

Abbas, Sascha; Linseisen, Jakob; Slanger, Tracy; Kropp, Silke; Mutschelknauss, Elke; Flesch-Janys, Dieter; Chang‐Claude, Jenny

doi:10.1158/1055-9965.epi-08-0162

Cited by 108 publications

(108 citation statements)

References 21 publications

(27 reference statements)

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“…The first study found no significant associations between either rs7041 or rs4588 and breast-cancer risk; however, this was among a relatively small sample of only 500 postmenopausal cases and 500 controls from the United States (22). The second study found the GC2 genotype (rs7041 TT and rs4588 AA combined genotypes) was significantly associated with reduced breast-cancer risk among 1,391 postmenopausal cases and 1,365 postmenopausal controls in Germany (21). Our results of a positive association between the rs7041 TT genotype and breast-cancer risk are not consistent with Abbas and colleagues (21), but they are in the expected direction if vitamin D is inversely associated with breast-cancer risk because this genotype is associated with lower 25(OH)D.…”

Section: Discussionmentioning

confidence: 94%

“…Most previous studies have investigated VDR variants only and although the FokI (rs2228570, previously rs10735810) and BsmI (rs1544410) SNPs have been associated with breast cancer risk, the associations are relatively weak and many studies have been limited by small sample size (12,13,20). Few studies have evaluated other genes related to vitamin D metabolism; only two breast cancer studies have evaluated GC SNPs (rs7041 and rs4588) with conflicting results (21,22). To the best of our knowledge, only one CYP24A1 SNP has been investigated (22) and no studies have evaluated other CYP genes or variants in any genes involved with vitamin D-uptake by mammary cells (e.g., LRP2 and CUBN).…”

Section: -Hydroxyvitamin D [25(oh)d]mentioning

confidence: 99%

“…Rare homozygous genotypes with frequencies below 5% were combined with the heterozygotes if the ORs were in the same direction. For comparability with previous literature, a combined GC genotype was derived from rs4588 and rs7041 using previously described methods (21). The multiplicative interaction between each vitamin D or calcium exposure variable and each genetic polymorphism was evaluated by the statistical significance (P < 0.05) of the likelihood ratio test comparing the models with and without the product term.…”

Section: Statistical Data Analysismentioning

confidence: 99%

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

Anderson

Cotterchio

Cole

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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.

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Section: Discussionmentioning

confidence: 94%

Section: -Hydroxyvitamin D [25(oh)d]mentioning

confidence: 99%

Section: Statistical Data Analysismentioning

confidence: 99%

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

Anderson

Cotterchio

Cole

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…31 Several previous studies on serum, plasma and urine enterolactone concentrations in postmenopausal women found inverse but not statistically significant associations with breast cancer risk 3,32 or no association. 17,[33][34][35] This could have been in part due to small sample sizes of each of these studies and corresponding limited statistical power to detect a possible inverse association of enterolactone. Our previous meta-analysis including seven published studies showed that high serum or urinary levels of enterolactone are negatively but not significantly associated with postmenopausal breast cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

Zaineddin

Vrieling

Buck

et al. 2011

Intl Journal of Cancer

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Lignans are a group of estrogenic compounds present in plants. Several epidemiological studies proposed that lignans may protect against breast cancer by exerting anticarcinogenic activity. Levels of enterolactone were determined in serum samples of 1,250 cases and 2,164 controls from a large population-based case-control study. We assessed the association between serum enterolactone and postmenopausal breast cancer risk using conditional logistic regression accounting for potential risk and confounding factors. Fractional polynomials were used to determine the function that best fitted the data. Moreover, we assessed heterogeneity by estrogen/progesterone/herceptin (ER/PR/HER2) status of the tumor. Additionally, a meta-analysis with seven further studies addressing enterolactone concentrations and breast cancer risk was performed. Postmenopausal breast cancer risk decreased with increasing serum enterolactone levels [highest compared to lowest quintile: [odds ratio 5 0.65; 95% confidence interval (CI) 0.52-0.83, p trend 5 <0.0001]. A significant inverse association for ER1/PR1 as well as ER2/PR2 tumors was observed, with a significantly stronger association for ER2/PR2 tumors (p heterogeneity 5 0.03). The association for ER2/PR2 tumors did not differ by expression of HER2 (p heterogeneity 5 0.3). The meta-analysis yielded a significant reduced pooled risk estimate of: 0.66; 95% CI: 0.55-0.77) comparing the highest to the lowest quantiles of enterolactone levels. We found strong evidence for a significant inverse association between serum enterolactone and postmenopausal breast cancer risk, which was stronger for ER2PR2 than for ER1PR1 tumors but not differential by further expression of HER2. The overall evidence together with other studies supports an inverse association between higher serum enterolactone levels and postmenopausal breast cancer risk.Phytoestrogens are a group of biologically active compounds that have been shown to protect against hormone-dependent cancers, in particular, breast cancer. 1-4 Their protective inverse association with breast cancer may be due to either estrogenic or antiestrogenic properties. [5][6][7][8] Because of their chemical structure, phytoestrogens can compete with endogenous estrogen for binding to the estrogen receptor (ER) of the tumor, thereby plausibly reducing the hormonal effect of the endogenous estrogens. 9 In addition to this, phytoestrogens also have antioxidative and antiproliferative properties and thereby may also reduce cancer risk. 10 The two main groups of phytoestrogens are the isoflavones and the lignans. Isoflavones, in particular, genistein, are mostly found in soy products. Only a few nonsoy plants contain isoflavones (e.g., legumes, grapefruit and raisins); but, at lower concentration, isoflavones do not importantly contribute to phytoestrogen intake in Western diets. 11,12 Plant lignans are widely present in whole grain, berries, vegetables, fruits, flaxseeds and other types of seeds and are the main source of phytoestrogens in Western populations....

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“…Moreover, a pooled analysis of published case-control studies did not show a significant association between GC rs2282679 and colorectal cancer (41). Furthermore, other studies, including Colon Cancer Family Registry (42), Cancer Prevention Study-II Nutrition Cohort (43), Marie Study (44), Nurses' Health Study (19), Rotterdam Study (15), Shanghai Breast Cancer Study (45), and Health Professionals Follow-up Study (46), did not show significant association between GC rs7041 and/or rs4588 and cancer at different sites as colon-rectum, pancreas, breast, endometrium, skin and prostate. Otherwise, data from the Breast and Prostate Cancer Cohort Consorthium (47) provided evidence of a significant association between the rs2282679 variant and prostate cancer risk, which is not confirmed by the present meta-analysis.…”

Section: Discussionmentioning

confidence: 97%

Meta-analysis of Vitamin D–Binding Protein and Cancer Risk

Tagliabue

Raimondi

Gandini

2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Epidemiologic evidence supported a role for vitamin D and vitamin D receptor (VDR) polymorphisms in cancer risk. Beyond VDR, the biologic effects of vitamin D are mediated by the vitamin D-binding protein (DBP), a key protein in vitamin D metabolism. Furthermore, the gene encoding the DBP (GC, group-specific component) has an important role in the vitamin D pathway. Several studies investigated DBP serologic levels and GC polymorphisms in association with cancer risk with controversial results. Thus, we carried out a meta-analysis to investigate these associations.Methods: We included 28 independent studies concerning the following tumors: basal cell carcinoma, bladder, breast, colon-rectum, endometrium, liver, esophagus, stomach, melanoma, pancreas, prostate, and kidney. Through random-effect models, we calculated the summary odds ratios (SOR) for serum DBP and the GC polymorphisms rs2282679, rs12512631, rs7041, rs4588, rs17467825, rs1155563, and rs1352844.

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TheGc2Allele of the Vitamin D Binding Protein Is Associated with a Decreased Postmenopausal Breast Cancer Risk, Independent of the Vitamin D Status

Cited by 108 publications

References 21 publications

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

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

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

Meta-analysis of Vitamin D–Binding Protein and Cancer Risk

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