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Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk.

ABSTRACT: The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) is important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis is that variant alleles in key genes involved in the IGF pathway will influence the development of endometrial cancer.We conducted a case-control study nested within the Nurses' Health Study (NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer.We observed an inverse association with IGFII rs3741211 and endometrial cancer risk (OR=0.79 (95% CI: 0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR=0.80 (95% CI: 0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and endometrial cancer risk (OR=0.81 (95%CI: 0.67, 0.98). However, we did not observe any statistically significant associations with the polymorphisms in IGFI and IGFBP1 and endometrial cancer risk.Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed.

SUBMITTER: McGrath M

PROVIDER: S-EPMC3238452 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk.

McGrath Monica M Lee I-Min IM Buring Julie J De Vivo Immaculata I

Gynecologic oncology 20110201 2

<h4>Objective</h4>The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) is important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ulti ...[more]

PMID: 21078522

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Project description:INTRODUCTION:Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, we examined the association between common genetic variation in this pathway and mammographic density. METHODS:We conducted a cross-sectional analysis among controls (n = 1,121) who were between the ages of 42 and 78 years at mammography, from a breast cancer case-control study nested within the Nurses' Health Study cohort. At the time of mammography, 204 women were premenopausal and 917 were postmenopausal. We genotyped 29 haplotype-tagging SNPs demonstrated to capture common genetic variation in IGF1, IGF binding protein (IGFBP)-1, and IGFBP-3. RESULTS:Common haplotype patterns in three of the four haplotype blocks spanning the gene encoding IGF1 were associated with mammographic density. Haplotype patterns in block 1 (p = 0.03), block 3 (p = 0.009), and block 4 (p = 0.007) were associated with mammographic density, whereas those in block 2 were not. None of the common haplotypes in the three haplotype blocks spanning the genes encoding IGFBP-1/IGFBP-3 were significantly associated with mammographic density. Two haplotype-tagging SNPs in IGF1, rs1520220 and rs2946834, showed a strong association with mammographic density. Those with the homozygous variant genotype for rs1520220 had a mean percentage mammographic density of 19.6% compared with those with the homozygous wild-type genotype, who had a mean percentage mammographic density of 27.9% (p for trend < 0.0001). Those that were homozygous variant for rs2946834 had a mean percentage mammographic density of 23.2% compared with those who were homozygous wild-type with a mean percentage mammographic density of 28.2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). CONCLUSION:Common genetic variation in IGF1 is strongly associated with percentage mammographic density.

Dataset Information

Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk.

Publications

Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk.

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