Influence of genomic variation in FTO at 16q12.2, MC4R at 18q22 and NRXN3 at 14q31 genes on breast cancer risk

Kusińska, Renata; Górniak, Patryk; Pastorczak, Agata; Fendler, Wojciech; Potemski, Piotr; Młynarski, Wojciech; Kordek, Radzisław

doi:10.1007/s11033-011-1053-2

Cited by 42 publications

(28 citation statements)

References 14 publications

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“…Although it is still not completely clear if the fact of relatively small (3-5 y) age difference between mentioned groups can really affect the results, the further investigation of this subject can have practical significance, considering, e.g., more often occurrence of NRXN3 (neurexin group) gene polymorphism, associated with obesity and cell adhesion, in the youngest group of breast cancer patients. 36 The drawback of the current study is relatively small number of probands in each group, which leads to the conclusion that it should be viewed as a pilot study. Nevertheless, the data obtained is significant and possibly stimulating for further investigation in this area, incorporating the evaluation of not only potential but also actual effects of metformin in comparison with the pattern of studied polymorphisms.…”

Section: Oct1_r61cmentioning

confidence: 94%

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer

Berstein

Iyevleva

Vasilyev³

et al. 2013

Cell Cycle

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Metformin is a well-known antidiabetic medication, which, besides diabetes, may be involved into modulation of other age-related pathologies, including cancer. The study concerns 12 gene polymorphisms divided into 2 groups consisting of 6 genes each. The first group was composed from so-called "standard" (S) polymorphisms, for which the connection with metabolic response to metformin is already established. The second group included polymorphisms of genes encoding proteins possibly connected with diabetes mellitus type 2 (DM2), impaired glucose tolerance or cancer and entitled here as "associated" (A). A total of 156 postmenopausal women (average age 60.7 ± 0.7) were included, 37 of them healthy, 64 with type DM2 and concurrent treatment-naïve cancer (mostly breast, endometrial or colorectal cancer), 32 with DM2 without cancer, and 23 with treatment-naïve cancer and normal glucose tolerance. The leading metformin response S-marker in combined group of DM2 patients was the CC variant of OCT1-R61C polymorphism of organic cation transporter protein 1 gene. In cancer patients without DM2, this position belonged to AC and AA genotypes of OCT1_rs622342 polymorphism. Among the A-polymorphisms, GA variant of sex hormone-binding globulin gene SHBG_D356N was less frequently observed in DM2 patients with or without cancer. Besides, in diabetics, the same polymorphic variant of SHBG as well as GC genotype of oxidized lipoprotein receptor OLR1_G501C and GG genotype of locus rs11065987 near BRAP gene were carried rather often in combination with "metformin-positive" variant of OCT1_R61C. In addition, carriers of OCT1_R61C and OCT1_rs622342 polymorphisms with potentially positive reaction to metformin had higher insulin resistance score (HOMA-IR) values. Received data lead to the conclusion that postmenopausal diabetics, both with and without cancer, differ in genetic stigmata of potential response to metformin less than they differ from cancer patients without DM2. As genetic polymorphisms associated with metabolic and anticancer metformin (and, possibly, phenformin) effects may be different, this subject requires further investigation.

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Section: Oct1_r61cmentioning

confidence: 94%

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer

Berstein

Iyevleva

Vasilyev³

et al. 2013

Cell Cycle

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“…A positive association was found only in the case of African American women [38]. Despite the fact that Kaklamani et al [39] reported a significant association between FTO rs1477196 and breast cancer risk in predominantly Caucasian patients, Kusinska et al [40] found no such relation with the FTO variants rs993909 and rs9930506 in a sample of 134 Polish women. The same negative result was obtained by Brooks et al when they tried to find a relationship between FTO variants associated with BMI and the subsequent risk of second primary breast cancer [41].…”

Section: Fto Polymorphisms and Cancermentioning

confidence: 97%

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview

Hernández-Caballero

Sierra-Ramírez

2014

Mol Biol Rep

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The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

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“…Several of these isoforms bind to ligands that include membrane-bound endogenous neuroligins and dystroglycans, soluble endogenous neurexophilins and a-latrotoxin spider neurotoxins [10], [18], [21]. Polymorphic site of NRXN3 gene (rs10146997) was significantly associated with higher risk of breast cancer development [22]. In addition, NRXN3 polymorphisms are associated with alcohol dependence [23].…”

Section: Introductionmentioning

confidence: 99%

FoxQ1 Promotes Glioma Cells Proliferation and Migration by Regulating NRXN3 Expression

Sun¹,

Cheng²,

Tu³

et al. 2013

PLoS ONE

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BackgroundForkhead box Q1 (FoxQ1) is a member of the forkhead transcription factor family, and it has recently been found to participate in cancer development. However, whether FoxQ1 expression contributes to glioma development and progression is not known. We investigate FoxQ1 expression in gliomas and the role of FoxQ1 during tumorgenesis.MethodsReverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to determine the FoxQ1 and Neurexins 3 (NRXN3) expression in gliomas. Chromatin immunoprecipitation (ChIP) and luciferase assays were used to determine the regulation between FoxQ1 and NRXN3. We established depleted FoxQ1 stable clones in U-87MG cells and overexpressed FoxQ1 stable clones in SW1088 cells. MTT and transwell were used to evaluate the ability of proliferation and migration, respectively.ResultsFoxQ1 mRNA and protein were up-regulated in gliomas and negatively related to the NRXN3 expression (r = −0.373, P = 0.042). FoxQ1 directly binds to NRXN3 promoter region and suppresses the promoter activity. Furthermore, the ability of proliferation and migration is reduced in depleted FoxQ1 cells.ConclusionFoxQ1 promotes glioma cell proliferation and migration by down-regulation of NRXN3 expression.

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Influence of genomic variation in FTO at 16q12.2, MC4R at 18q22 and NRXN3 at 14q31 genes on breast cancer risk

Cited by 42 publications

References 14 publications

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview

FoxQ1 Promotes Glioma Cells Proliferation and Migration by Regulating NRXN3 Expression

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