Family-based genetic association study of insulin-like growth factor I microsatellite markers and premenopausal breast cancer risk

Fehringer, Gordon; Boyd, Norman F.; Knight, Julia A.; Paterson, Andrew D.; Dite, Gillian S.; Giles, Graham G.; Southey, Melissa C.; Andrulis, Irene L.; Hopper, John L.; Özçelik, Hilmi

doi:10.1007/s10549-009-0336-y

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…Furthermore, MSI has been noted as an earlier step in the CRC progression pathway in >90% of hereditary non-polyposis colorectal cancer (HNPCC) patients and in 15–20% of sporadic cases (2,13). Similar forms of instability have been diagnosed in numerous other tumors (16,17). These findings highlight the higher tendency of MMR-deficient tissues to accumulate mutations, develop MSI and eventually progress to a cancerous state.…”

Section: Introductionsupporting

confidence: 74%

Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Kamat

Khidhir²,

Alashari

et al. 2013

Oncology Letters

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Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1–50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0–25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7–39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher’s exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender.

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Section: Introductionsupporting

confidence: 74%

Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Kamat

Khidhir²,

Alashari

et al. 2013

Oncology Letters

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“…Results of early studies also suggested an association between the absence of the common IGF1 19 CA repeat allele and increased breast cancer risk (26, 39). However, recent reports, including several meta-analyses, have found no association between the length of this CA repeat and the risk of developing breast cancer (18, 22, 40). In cervical cancer, a recent study found significant differences in the repeat length between some types of cervical cancer and control groups (41), whereas no association was found with cervical cancer risk in an earlier study (42).…”

Section: Introductionmentioning

confidence: 93%

“…Also, mammographic density, which is a strong predictor of breast cancer risk, has been correlated with plasma IGF1 levels in premenopausal women (21). Hence, polymorphisms in the IGF1 gene have been extensively analysed in relation to breast cancer risk, although the results have been variable and sometimes contradictory (19, 22, 23, 24, 25), most likely due to differences in ethnic composition of the populations studied (26). …”

Section: Introductionmentioning

confidence: 99%

A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

Bolton

Avery‐Kiejda

Holliday

et al. 2016

Endocrine Connections

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Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.

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Polymorphic CA repeat length in insulin-like growth factor 1 and risk of breast cancer in Iranian women

2011

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To evaluate the association between breast cancer and cytosine-adenine (CA) dinucleotide repeat length polymorphisms in the promoter region of the Insulin-like Growth Factor 1 (IGF-1) gene, a case-control study of 215 breast cancer patients and 224 controls was conducted in Iranian women. The most common allele and genotype in both controls and patients were an allele length of 19 and a homozygous genotype of (CA)(19)/(CA)(19). Women with two alleles longer than 19 were found to be at a higher risk of breast cancer with an odds ratio of 4.1 (P = 0.0002). In contrast, women with two alleles shorter than 20 were at lower risk of breast cancer. These results suggest a novel association between CA repeat length in IGF-1 and risk of breast cancer.

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Family-based genetic association study of insulin-like growth factor I microsatellite markers and premenopausal breast cancer risk

Cited by 4 publications

References 39 publications

Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

Polymorphic CA repeat length in insulin-like growth factor 1 and risk of breast cancer in Iranian women

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