Shang Cao1, Feiran Wei2, Jinyi Zhou3, Zheng Zhu3, Wei Li1, Ming Wu4,5. 1. Department of Epidemiology and Health Statistics, Southeast University, Nanjing, China. 2. Department of Oncology, Southeast University, Nanjing, China. 3. Department of Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Road 72th, Nanjing, 210009, Jiangsu, China. 4. Department of Epidemiology and Health Statistics, Southeast University, Nanjing, China. jswuming@vip.sina.com. 5. Department of Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Road 72th, Nanjing, 210009, Jiangsu, China. jswuming@vip.sina.com.
Abstract
PURPOSE: Vitamin D (VD) metabolism regulates adipose tissue, lipogenesis inflammation, and tumor growth. CYP24A1 is the key enzyme for metabolic inactivation of active VD (1,25(OH)2D3). We examined whether common germline single nucleotide polymorphisms (SNPs) in the CYP24A1 gene could affect the association between adult weight gain and breast cancer (BC) risk. METHODS: The population-based case-control study included 818 patients with primary BC and 935 residence and age matched healthy controls. We studied the relationships between CYP24A1 gene SNPs (rs2209314, rs2585428, rs2762941, rs3787555, rs4809959, rs73913757, rs912505, and rs927a650), adult weight change and BC risk. Gene-weight change interactions were analyzed. RESULTS: Neither of CYP24A1 gene SNPs was associated with BC risk in the study participants. However, we found consistent gene-weight interactions with increasing adult weight gain for CYP24A1-rs2762941 (P-interaction = 0.0089) and CYP24A1-rs927650 (P-interaction = 0.0283). Adult weight gain has a higher premenopausal BC risk with double variant T alleles of rs927650 compared to women carrying at least one wild-type C allele (OR for TT = 1.82, 95% CI 1.10-3.01; for CT = 0.93, 95% CI 0.76-1.14; for CC = 1.12 95% CI 0.93-1.35). Women with double wild-type A alleles were at a higher postmenopausal BC risk compared to those carrying at least one variant-type G allele (OR for AA = 1.51, 95% CI 1.29-1.76; for AG = 1.13, 95% CI 0.98-1.30; for GG = 1.22 95% CI 0.95-1.57). When stratified by CYP24A1 SNPs genotypes, weight gain in adulthood increased postmenopausal BC risk of women with homozygous allele compared to women with heterozygotes allele. CONCLUSION: Significant interactions of weight change with CYP24A1 polymorphisms suggest CYP24A1 as a potential link between weight change and BC risk and the possibility that the impact of adult weight gain on postmenopausal BC risk may be enhanced by homozygous alleles of CYP24A1 SNPs.
PURPOSE:Vitamin D (VD) metabolism regulates adipose tissue, lipogenesis inflammation, and tumor growth. CYP24A1 is the key enzyme for metabolic inactivation of active VD (1,25(OH)2D3). We examined whether common germline single nucleotide polymorphisms (SNPs) in the CYP24A1 gene could affect the association between adult weight gain and breast cancer (BC) risk. METHODS: The population-based case-control study included 818 patients with primary BC and 935 residence and age matched healthy controls. We studied the relationships between CYP24A1 gene SNPs (rs2209314, rs2585428, rs2762941, rs3787555, rs4809959, rs73913757, rs912505, and rs927a650), adult weight change and BC risk. Gene-weight change interactions were analyzed. RESULTS: Neither of CYP24A1 gene SNPs was associated with BC risk in the study participants. However, we found consistent gene-weight interactions with increasing adult weight gain for CYP24A1-rs2762941 (P-interaction = 0.0089) and CYP24A1-rs927650 (P-interaction = 0.0283). Adult weight gain has a higher premenopausal BC risk with double variant T alleles of rs927650 compared to women carrying at least one wild-type C allele (OR for TT = 1.82, 95% CI 1.10-3.01; for CT = 0.93, 95% CI 0.76-1.14; for CC = 1.12 95% CI 0.93-1.35). Women with double wild-type A alleles were at a higher postmenopausal BC risk compared to those carrying at least one variant-type G allele (OR for AA = 1.51, 95% CI 1.29-1.76; for AG = 1.13, 95% CI 0.98-1.30; for GG = 1.22 95% CI 0.95-1.57). When stratified by CYP24A1 SNPs genotypes, weight gain in adulthood increased postmenopausal BC risk of women with homozygous allele compared to women with heterozygotes allele. CONCLUSION: Significant interactions of weight change with CYP24A1 polymorphisms suggest CYP24A1 as a potential link between weight change and BC risk and the possibility that the impact of adult weight gain on postmenopausal BC risk may be enhanced by homozygous alleles of CYP24A1 SNPs.
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Keywords:
Breast cancer; CYP24A1; Single nucleotide polymorphisms; Weight change