Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study

Yao, Song; Zirpoli, Gary; Bovbjerg, Dana H.; Jandorf, Lina; Hong, Chi Chen; Zhao, Hua; Sucheston, Lara; Tang, Li; Roberts, Michelle; Ciupak, Gregory; Davis, Warren; Hwang, Helena; Johnson, Candace S.; Trump, Donald L.; McCann, Susan E.; Ademuyiwa, Foluso O.; Pawlish, Karen; Bandera, Elisa V.; Ambrosone, Christine B.

doi:10.1186/bcr3162

Cited by 75 publications

(23 citation statements)

References 45 publications

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“…The lack of consistency of the associations in AA and EA women is not unexpected. In the WCHS, we previously found that genetic associations in several biological pathways, including several vitamin D‐related genes, differed between AA and EA women. These data suggest that associations between genetic variants in vitamin D‐related pathways and breast cancer risk in AAs may be different from those in EAs.…”

Section: Discussionmentioning

confidence: 99%

“…AAs have a high rate of vitamin D deficiency, likely due, in part, to dark skin pigmentation which blocks UVB light, and, to a lesser extent, lactose intolerance which may limit vitamin D intake from fortified dairy products . Our previous studies have also demonstrated wide‐spread differences in variant frequency and linkage disequilibrium (LD) in vitamin D‐related genes between AA and EA populations . It is thus important to understand whether ancestral variations in vitamin D‐related genes in AAs, which were shaped over millennia in sun exposure‐abundant Africa, would put AA women at high risk of breast cancer in a Northern hemisphere environment where sun exposure is limited and seasonally fluctuates …”

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confidence: 99%

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Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

Yao

Haddad

et al. 2015

Int. J. Cancer

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Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER− breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER− cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10−5, gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10−4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

Yao

Haddad

et al. 2015

Int. J. Cancer

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“…The Women's Circle of Health Study (WCHS), a case–control study designed to evaluate risk factors for aggressive breast cancer in AA women, was conducted in the metropolitan New York City area and seven counties in New Jersey and has been previously described in detail . Eligible participants included English‐speaking AA and EA women ages 20 to 75 years, with no previous history of cancer other than non‐melanoma skin cancer, who were diagnosed with primary, histologically confirmed breast cancer.…”

Section: Methodsmentioning

confidence: 99%

Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry

Quan

Gong

Yao

et al. 2013

Intl Journal of Cancer

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Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA), and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n=335 cases) and 864 AA (n=458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1307 EAs and 1365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469), associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend=0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER positive breast cancers among EAs and marginally among AAs. Among AA women only, IL15 rs10833 and IL15RA rs2296135 were associated with ER positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status.

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“…Studies of single nucleotide polymorphisms (SNPs) in GC found no significant association with breast cancer risk [25,28,29]. CYP27B1 and CYP24A1 are involved in the activation and degradation of 25(OH)D and 1,25(OH) 2 D. Only five studies examined the association between SNPs on these genes and breast cancer risk [25,28–31]. A review suggests that some SNPs on these genes may be associated with breast cancer risk, but results are inconclusive [32].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk

Reimers

Crew

Bradshaw

et al. 2014

Cancer Causes Control

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Purpose Studies of vitamin D pathway genetic variants in relation to cancer risk have been inconsistent. We examined associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk. Methods In a population-based case-control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). Results Among CYP24A1 polymorphisms, rs6068816 was associated with a 72% reduction in breast cancer risk (TT vs. CC, OR: 0.28, 95%CI: 0.10–0.76; ptrend=0.01), but for rs13038432, the 46% decrease included the null value (GG vs. AA, OR: 0.54, 95%CI: 0.17–1.67; ptrend=0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR: 1.34, 95% CI: 0.92–1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26% risk reduction (TT vs. CC, OR: 0.74, 95%CI: 0.56–0.98; ptrend=0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR: 0.43, 95%CI: 0.27–0.68) among women with the common allele for CYP24A, rs927650 (p for interaction on a multiplicative scale=0.01). Conclusion Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.

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Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study

Cited by 75 publications

References 45 publications

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry

Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk

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