| 1. |
- Onay, Ummiye V., et al.
(författare)
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Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk
- 2008
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription. METHODS: In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins. RESULTS: Here, we have shown that the high enzymatic activity genotype of CCND1High (AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0-1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01-1.84)]. The heterozygous COMTMedium (MetVal) and the high enzymatic activity of COMTHigh (ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07-1.68)] and [OR: 1.4, 95%CI (1.07-1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMTHigh (ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73-1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: 2.22, 95%CI (1.49-3.28)] and Finland [OR: 1.73, 95%CI (1.08-2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity. CONCLUSION: Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.
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| 2. |
- Sovio, Ulla, et al.
(författare)
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Association between Common Variation at the FTO Locus and Changes in Body Mass Index from Infancy to Late Childhood : The Complex Nature of Genetic Association through Growth and Development
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:2, s. e1001307-
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Tidskriftsartikel (refereegranskat)abstract
- An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10−20) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10−23). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (−0.40% (95% CI: −0.74, −0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (−4.72% (−5.81, −3.63), p = 10−17), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.
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| 3. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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