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)

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.

Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis

“…The features of these four SNPs (in six different studies), which included cancer type (breast, colorectal, esophageal, and non-Hodgkin’s lymphoma), ethnicity, number of cases and controls, calculated statistical power, minor allele frequency (MAF) and HWE are summarised in Table 2. The studies, that included rs696217 [10–14,23], rs4684677 [10–13], rs2075356 [11,12,23] and rs572169 [11,14,23] had statistical power of >83%, indicating that these studies were not underpowered (Table 2). Control frequencies in two component studies [10,14] deviated from the HWE in the rs4684677 and rs572169 polymorphisms (Table 2).…”

“…Control frequencies in two component studies [10,14] deviated from the HWE in the rs4684677 and rs572169 polymorphisms (Table 2). Furthermore, three studies demonstrated borderline deviation from the HWE (p = 0.05-0.06) for the rs69621, rs2075356 and rs572169 polymorphisms [10,11,23].

Figure 1 Flowchart of literature search.

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A Sequence Polymorphism in miR-608 Predicts Recurrence after Radiotherapy for Nasopharyngeal Carcinoma

“…Associations between genotypes and TTR and OS were estimated using the Kaplan-Meier method, and statistical significance was determined using the log-rank test (34). For the functional analyses, data were presented by using mean AE SEM; the comparison of mean between two groups was conducted by using Student t test; statistical comparisons of more than two groups were conducted using the one-way ANOVA (35), and then least-significant difference (LSD) for multiple comparisons. The statistical analyses were conducted using STATA software (version 10; STATA Corporation).…”

Systematic functional regulatory assessment of disease-associated variants

“…As an example, rs171407, a SNP previously reported to be associated with breast cancer (16) and linked (r 2 = 0.812) to rs35683, a variant associated with type 2 diabetes (17), shows significant genotype-specific association with NFκB binding in the eight individuals queried (r = −0.88; P = 0.0038; Fig. 4A).…”