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- Dossus, Laure, et al.
(författare)
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Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1360-1366
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.
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| 2. |
- Johansson, Mattias, et al.
(författare)
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Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Umea Univ Hosp, Dept Surgical & Perioperative Sci, S-90185 Umea, Sweden. Umea Univ Hosp, Dept Urol Androl, S-90185 Umea, Sweden. Umea Univ Hosp, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. Int Agcy Res Canc, F-69372 Lyon, France. Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-85500 Utrecht, Netherlands. Harvard Univ, Dept Epidemiol, Boston, MA 02215 USA. German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 92:12, s. 4820-4826
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3 ' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I. Materials and Methods: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3 ' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden ( CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort ( NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3 ' region of the IGF-I gene in relation to circulating IGF-I levels. Results: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC ( P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I ( P = 0.001 and P < 0.0001, respectively). Conclusions: Genetic variation in the 3 ' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.
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| 3. |
- Sinilnikova, Olga M., et al.
(författare)
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Haplotype-based analysis of common variation in the acetyl-CoA carboxyiase alpha gene and breast cancer risk: A case-control study nested within the European prospective investigation into cancer and nutrition
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:3, s. 409-415
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Tidskriftsartikel (refereegranskat)abstract
- A key fatty acid synthesis enzyme, acetyl-CoA carboxylase alpha(ACC-alpha), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-alpha common genetic variation (allele frequency > 5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotypetagging polymorphisms efficiently capturing common variation within 325 kb of ACC-alpha and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis.
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| 5. |
- Verheus, Martijn, et al.
(författare)
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Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 112:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. OBJECTIVES: We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. DESIGN AND METHODS: Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. RESULTS: The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and higher. CONCLUSION: Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.
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