Haplotype-Based Association Studies of <i>IGFBP1</i> and <i>IGFBP3</i> with Prostate and Breast Cancer Risk: The Multiethnic Cohort

Cheng, Iona; Penney, Kathryn L.; Stram, Daniel O.; Marchand, Loı̈c Le; Giorgi, Elena E.; Haiman, Christopher A.; Kolonel, Laurence N.; Pike, Malcolm C.; Hirschhorn, Joel N.; Henderson, Brian E.; Freedman, Matthew L.

doi:10.1158/1055-9965.epi-06-0361

Cited by 43 publications

(67 citation statements)

References 22 publications

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“…In our study, we did not observe any association of the Ile253Met polymorphism with the risk of CRC. This result is in concordance with a recent study by Cheng et al (2006) in which they conducted a haplotype-based study and found no association with the risk of prostate and breast cancer.…”

Section: Discussionsupporting

confidence: 92%

“…In such a region, assaying for one marker would generally provide genotype information of all the others (Bennett & Todd 1996, Stephens et al 2005, Cheng et al 2006). To observe a dominant effect, our study had a 90% power to detect an OR of 1.4.…”

Section: Discussionmentioning

confidence: 99%

“…In the IGFBPI gene, the only non-synonymous SNP Ile253Met (rs4619) was in 100% LD with all the other SNPs along the entire IGFBPI gene region as previously shown by Cheng et al (2006) and therefore, we selected it for further analysis. In the INSR gene, four promoter and eight coding region SNPs were confirmed.…”

Section: Snp Selectionmentioning

confidence: 99%

“…So far, prostate cancer is the most intensively studied cancer with regard to the effect of polymorphisms in the INS, IRS1, IRS2, and IGFBPI genes on cancer susceptibility (Ho et al 2003, Claeys et al 2005, Li et al 2005, Neuhausen et al 2005, Stephens et al 2005, Cheng et al 2006. Only one study has focused on IRS1 and IRS2 polymorphisms and the risk of CRC (Slattery et al 2004).…”

Section: Introductionmentioning

confidence: 99%

“…High LD has been reported across the entire IGFBPI gene (Stephens et al 2005, Cheng et al 2006. The Ile253Met SNP is the only validated non-synonymous SNP and has been associated with diabetic nephropathy (Stephens et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect

Pechlivanis¹,

Pardini²,

Bermejo³

et al. 2007

Endocr Relat Cancer

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Western lifestyle leading to obesity and type 2 diabetes has been associated with increased risk of colorectal cancer (CRC). Diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling may play a plausible role in the development of CRC. We hypothesized that functional polymorphisms in the insulin pathway genes INS, INSR, IGFBPI, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with CRC. We studied the association of five single nucleotide polymorphisms (SNPs) with the risk of CRC using a hospital-based case-control design with 712 cases and 748 controls from the Czech Republic. The INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk (odds ratios (OR) 0.71, 95% confidence interval (CI) 0.54-0.93). Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk among the INSR-603G allele carriers (OR 0.28,. SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Snp Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect

Pechlivanis¹,

Pardini²,

Bermejo³

et al. 2007

Endocr Relat Cancer

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Genetic variation and circulating levels of IGF‐I and IGFBP‐3 in relation to risk of proliferative benign breast disease

Colditz

Willett

et al. 2009

Intl Journal of Cancer

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Insulin-like growth factor-I (IGF-I) and its major binding protein IGFBP-3 have been implicated in breast carcinogenesis. We examined the associations between genetic variants and circulating levels of IGF-I and IGFBP-3 with proliferative benign breast disease (BBD), a marker of increased breast cancer risk, in the Nurses' Health Study II (NHSII). Participants were 359 pathology-confirmed proliferative BBD cases and 359 matched controls. Circulating IGF-I and IGFBP-3 levels were measured in blood samples collected between 1996 and 1999. Thirty single nucleotide polymorphisms (SNPs) in IGF-I, IGFBP-1, and IGFBP-3 genes were selected using a haplotype tagging approach and genotyped in cases and controls. Circulating IGF-I levels were not associated with proliferative BBD risk. Higher circulating IGFBP-3 levels were significantly associated with increased risk of proliferative BBD (highest vs. lowest quartile odds ratio (OR) [95% confidence interval (CI)], 1.70 (1.06-2.72); p-trend 5 0.03). The minor alleles of 2 IGFBP-3 SNPs were associated with lower proliferative BBD risk (homozygous variant vs. homozygous wild-type OR (95% CI): rs3110697: 0.6 (0.4-0.9), p-trend 5 0.02; rs2132570: 0.2 (0.1-0.6), p-trend 5 0.02). Three other IGFBP-3 SNPs (rs2854744, rs2960436 and rs2854746) were significantly associated with circulating IGFBP-3 levels (p < 0.01). Although these SNPs were not significantly associated with proliferative BBD risk, there was suggestive evidence that the alleles associated with higher circulating IGFBP-3 levels were also associated with higher risk of proliferative BBD. These results suggest that genetic variants and circulating levels of IGFBP-3 may play a role in the early stage of breast carcinogenesis.Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among women in the United States.1 Benign breast disease (BBD) comprises a multiplicity of component histologic subtypes among which proliferative BBD is a marker of increased breast cancer risk and may even be in the pathway for a subset of breast cancers.2 Women whose biopsies show proliferative changes without atypia have a 1.3-1.9-fold greater risk of subsequent breast cancer than women with nonproliferative lesions, and women with atypical hyperplasia (AH) have a 3.9-13-fold greater risk.

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IGF1, IGFBP1, and IGFBP3 genes and mammographic density: The Multiethnic Cohort

Verheus

Maskarinec

Woolcott

et al. 2010

Intl Journal of Cancer

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Insulin-like growth factor-I (IGF-I) has mitogenic properties and stimulates cell growth. In this analysis, we investigated the relation between common genetic variation in IGF1, IGFBP1, and IGFBP3, and mammographic density among 819 women of Hawaiian, European, and Japanese ancestry from the Multiethnic Cohort Study. Mammographic density was assessed using a quantitative computer-assisted method. Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (26 tag SNPs) and IGFBP1/IGFBP3 (22 tag SNPs) were genotyped among the 819 women. Mixed models were conducted to evaluate the associations between genetic variation and mammographic density. Two SNPs were borderline statistical significantly associated with mammographic density: rs35539615 on IGFBP1 (p 5 0.05) and rs2453839 on IGFBP3 (p 5 0.01). Rs35767on IGF1 (p 5 0.03) was also associated with mammographic density, although in opposite direction of what was expected from previous findings with IGF-I levels. The majority of SNPs were, however, not associated with mammographic density. Analyses stratified by ethnicity showed similar results as the overall analyses for IGF1 and IGFBP1. However, for 4 SNPs in the IGFBP3 gene, the minor allele was associated with lower mammographic density in Japanese Americans and higher mammographic density in Caucasians. Given the large number of SNPs tested and the few borderline significant results, we only found weak evidence that genetic variations in IGFBP1 or IGFBP3 may be related to mammographic density. Ethnicity may modify these relations.Insulin-like growth factor-I (IGF-I) promotes proliferation and inhibits apoptosis in both normal breast cells and breast cancer cell lines. The bioavailability of IGF-I is determined by 6 binding proteins. IGFBP-3 is the predominant binding protein and has been described to also directly affect breast cancer risk in an IGF-I independent manner. 1 In several epidemiologic studies, circulating IGF-I levels were associated with higher breast cancer risk among pre-but not post-menopausal women.2-4 However, more recent results from the EPIC study and the Nurses Health Study (NHS)-II did not show an association between IGF-I levels and breast cancer risk among younger women. 5,6The amount of stromal and glandular tissues of the breast relative to the surrounding fatty tissue can be estimated using mammographic images.7 A high percentage of radiologically dense tissues (percent density) is a strong breast cancer risk factor and is, therefore, often used in etiologic studies as biomarker for breast cancer risk. 8 Circulating levels of IGF-I have been found to be related to mammographic density in premenopausal women in past epidemiological studies, [9][10][11] although this was not confirmed in recent reports. 12,13 In postmenopausal women, this relation does not seem to exist.

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Haplotype-Based Association Studies of IGFBP1 and IGFBP3 with Prostate and Breast Cancer Risk: The Multiethnic Cohort

Cited by 43 publications

References 22 publications

Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect

Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect

Genetic variation and circulating levels of IGF‐I and IGFBP‐3 in relation to risk of proliferative benign breast disease

IGF1, IGFBP1, and IGFBP3 genes and mammographic density: The Multiethnic Cohort

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