Mammographic breast density and IGF-1 gene polymorphisms rs1520220, rs2946834 and rs6219 in Polish women
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ABSTRACT: Aim of the study
The aim of the study was to analyze three single nucleotide polymorphisms – rs1520220, rs2946834, rs6219 – of the IGF-1 gene in the context of breast mammographic density. Material and methods
The research material included 202 samples of the peripheral blood of women with increased mammographic breast density and 238 samples of the epithelium from the oral mucosa of women without diagnosed pathological changes of the breast and with no family history of breast and/or ovarian cancer. The real-time polymerase chain reaction method was applied for analysis of polymorphisms. Results
rs1520220 polymorphism was associated with increased mammographic density of the breasts. The presence of the CC genotype in the IGF-1 gene increased the risk of developing higher breast density visible in mammography by 2.43-fold. CC homozygotes (rs1520220) correlated with higher Breast Imaging-Reporting and Data System scale (3 vs. 4 and 5) (OR = 5.6; 95% CI: 1.82–16.3, p = 0.001). In the present study no relationship was detected between rs6219 and rs2946834 polymorphism and mammographic breast density. Conclusions
The results suggest that the rs1520220 polymorphism of the IGF-1 gene plays an important role in the occurrence of increased mammographic breast density.
SUBMITTER: Smolarz B
PROVIDER: S-EPMC8547182 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE: Recent work has suggested that insulin-like growth factor 1 (IGF-1) gene polymorphisms are genetically linked with high-grade myopia (HM), which is a complex-trait eye disorder in which numerous candidate loci and genes are thought to play a role. We investigated whether the IGF-1 single nucleotide polymorphisms (SNPs) rs6214, rs10860860, and rs2946834 are associated with HM (?-6.0 diopters [D]) and any myopia (?-0.5 D) phenotype in Polish families. METHODS: Forty-two multiplex HM Polish families, of whom 127 had HM, participated in the study. All of the family members (n=306) underwent a detailed ophthalmic examination, including axial length measurements. The IGF-1 SNPs rs6214, rs10860860, and rs2946834 were evaluated by PCR-RFLP and direct sequencing methods. Both Family-Based Association Test (FBAT) and family-based Pedigree Disequilibrium Test (PDT) were used to examine the potential association of the IGF-1 SNPs rs6214, rs10860860, and rs2946834 with HM or any myopia. To determine the distribution of the HM-associated SNPs rs6214 and rs10860860, 543 unrelated individuals from the general Polish population were also analyzed. RESULTS: We found no significant association between the IGF-1 SNPs rs6214, rs10860860, and rs2946834 and HM or any myopia phenotype in Polish HM families. In the general Polish population, the minor allele frequencies of the SNPs rs6214 and rs10860860 did not deviate significantly from the distribution reported for European populations (p=0.629). In the FBAT analysis under the dominant model, the haplotype consisted of T allele of rs10860860, with C allele of rs2946834 of IGF-1 was found less frequently transmitted to HM individuals (p=0.0065), pointing to a nonassociated or protective haplotype. CONCLUSIONS: Our results do not support recent studies reporting an association of the SNPs rs6214, rs10860860, and rs2946834 in the IGF-1 gene with HM and any myopia phenotypes. Further replication studies involving other populations are needed to investigate the possible role of IGF-1 as a potential myopia candidate gene.
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Project description:Sex hormones are metabolized to less active compounds via (a) glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women.One hundred seventy-five women ages 40 to 45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1.Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared with women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (P = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density.Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women.
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Project description:IntroductionWe examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17beta-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women.MethodsThe Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI).ResultsAfter multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01).ConclusionsSNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.
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