Cytosine-adenine Repeat Research Articles

Polymorphisms in genes involved in breast cancer among Iranian patients.

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes (STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3, sirtuin-3, NKG2D).Cytosine-adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1), rs6505162, tri-nucleotide (GCGTGFBR1). We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Association between CA repeat polymorphism in IGF1 gene promoter and colorectal cancer risk in a native Chinese population.

Insulin-like growth factor 1 (IGF1) is implicated in normal cell growth. It has been reported that IGF1 has a mitogenic and anti-apoptotic effect on colorectal cancer cells. However, results of studies on the association between cytosine-adenine (CA) repeat polymorphism in IGF1 gene promoter and colorectal cancer (CRC) risk are inconsistent. We aimed to evaluate the association between CA repeat polymorphism and CRC risk, as well as the relationship with the clinicopathological characteristics of CRC and circulating IGF1 level in a native Chinese population. There were 734 participants who were native Chinese in this case-control study, including 367 CRC cases and 367 age- and sex-matched controls. CA repeat polymorphism was genotyped by PCR and fragment analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by unconditional logistic regression analysis. Circulating level of IGF1 in cases was significantly higher than that in controls (P = 0.002), particularly in males. Less than 38 CA repeats were associated with decreased CRC risk after adjusting for age and sex (37 versus 38 CA repeats: OR = 0.45; 95%CI = 0.26-0.78), especially in males. (CA)18/19 genotype showed approximately half reduced CRC risk comparing to (CA)19/19 genotype (OR = 0.46; 95%CI = 0.25-0.85). There was a significant association between the sum of CA repeats and degree of differentiation of CRC (P = 0.044). We observed a trend that circulating level of IGF1 in individuals with CA ≤ 38 repeats was lower than that in individuals with CA > 38 repeats with a borderline statistically significance in overall and males. In conclusion, our findings support the possible role of CA repeat polymorphism in CRC risk.

Relationship between cytosine-adenine repeat polymorphism of ADAMTS9 gene and clinical and radiologic severity of knee osteoarthritis.

The aim of this study is to determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of osteoarthritis (OA). A total of 110 participants, including those with primary knee OA and healthy controls were enrolled in the study. Patients were stratified into two groups using the Kellgren-Lawrence staging (K-L staging) as group 1 for controls and mild OA and group 2 for moderate and severe OA. Genetic analyses were performed to determine the CA repeat length in ADAMTS9 gene. Twenty CA repeats were found to be statistically significant for differentiating groups 1 and 2 (P = 0.020). Age was the most significant risk factor involved, followed by ≥ 20 CA repeats and body mass index (P < 0.05). CA repeat length of ≥ 20 showed a 6.1-fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of < 20 (P = 0.004). In conclusion, the CA repeat length of ≥ 20 has a six-fold increase in probability for having severe OA. ADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. Being the first in the literature reporting the CA repeat in the promotor region of ADAMTS9 gene in patients with OA, our study could be highlighted further in future research with larger sample size.

Citosine-Adenine-Repeat Microsatellite of 11β-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children.

The impairment of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2) results in an inefficient conversion of cortisol to cortisone, which triggers hypertension. Cytosine-adenine repeat (CA repeat) microsatellite has been associated with low HSD11B2 gene expression. To determine whether the CA-repeat length in intron 1 affect the serum cortisol to cortisone (F/E) ratio and/or blood pressure (BP) levels in pediatric subjects. Eighty-one hypertensive (HT) and 117 normotensive (NT) subjects participated in this study. We measured BP levels, as well as the F and E and F/E ratio in morning sera and 12-hour urine samples. The length of CA repeats was determined through fragment analysis. We compared the allele distribution between the HT and NT groups, and the patients were dichotomized into groups with short alleles (S) (<21 CA repeats) or long alleles (L), and also in groups according genotype (allele combination: S/S and S/L + L/L). We found no differences in the distribution of CA-repeat allelic length between the NT and HT groups (P = 0.7807), and there was no correlation between the CA-repeat allelic length and BP (P = 0.1151) levels or the serum F/E ratio (P = 0.6778). However, the serum F/E ratio was higher in the HT group than in the NT group (P = 0.0251). The serum F/E ratio was associated with systolic BP index independent of body mass index only in HT group. The CA-repeat length did not influence BP levels or serum F/E ratios in pediatric subjects. However, the serum F/E ratio was associated with BP, suggesting a role of 11βHSD2 in mineralocorticoid hypertension.

Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervical cancer.

THU0470 The Relationship between Cytosine-Adenine Repeat Polymorphism in the Promoter Region of Adamts 9 (A Distintegrinand Metalloproteinase with Thrombospondin Motif 9) Gene and Clinical and Radiologic Severity of Knee Osteoarthritis

BackgroundThe relationship between ADAMTS genes and osteoarthritis (OA) may be crucial since these genes and their products may be used as biomarkers for prognosis and treatment of OA.ObjectivesTo determine the...

Identification of a Predictive Biomarker for the Beneficial Effect of Keishibukuryogan, a Kampo (Japanese Traditional) Medicine, on Patients with Climacteric Syndrome

Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor β gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients' profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients' climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients' profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.

Is β the α Dog in Estrogen Receptor–Mediated Protection From Hypertension?

See related article, pp 1255–1262 The onset of hypertension occurs earlier in men than in women. Moreover, the magnitude of hypertension is greater in men than in women across diverse mammalian species and experimental models.1 17β-estradiol (E2) is implicated in this female protection because ovarian hormone loss is associated with increased arterial pressure while E2 replacement can prevent this effect. Creation of mice deficient in estrogen receptors (ERα and ERβ) and the development of ER subtype-selective ligands have enabled investigation of ER subtypes in hypertension. A study of Japanese women revealed an association between hypertension and a cytosine-adenine repeat polymorphism in the ERβ gene.2 This association was strengthened by studies in ERβ-deficient mice, which developed hypertension as they aged and exhibited abnormal ion channel function in vascular smooth muscle cells suggesting ERβ attenuated the age-associated hypertension by preserving vascular function.3 Pharmacological studies supported these conclusions by demonstrating selective agonists of ERβ-reduced arterial pressure in ovariectomized spontaneously hypertensive rats under conditions in which ERα-selective agonists did not.4 Furthermore, activation of ERβ improved nitric oxide–dependent vasorelaxation, increased cardiac output, and attenuated cardiac hypertrophy; however, this study did not determine whether these effects were peripherally or centrally mediated. Previously, Xue et al5 showed that central but not peripheral infusions of a nonselective ER antagonist into mice augmented the pressor effects of angiotensin II (Ang II), thereby underscoring the importance of central ERs in blood pressure modulation. In this issue, Xue et al6 used small interference RNA via an adeno-associated virus to selectively knockdown ERα and ERβ in specific brain nuclei. Mice with ERβ deficiency in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) exhibited increased sympathetic activity …

Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis

BackgroundThe insulin-like growth factor-1 (IGF-1) plays an important role in growth of prostate cancer (PCa) cells and facilitating the development and progression of PCa. This study aimed to evaluate the association of polymorphisms in three linkage disequilibrium (LD) blocks of the IGF-1 on the survival of metastatic PCa patients.MethodsA total of 215 patients with bone metastases at initial presentation were included in this study. The cytosine-adenine (CA) repeat polymorphism and rs12423791 were selected as representative polymorphisms in the LD blocks 1 and 2, respectively. Haplotype in the LD block 3 was analyzed using two tag single nucleotide polymorphisms (SNPs), rs6220 and rs7136446. Cancer-specific survival rate was estimated from the Kaplan-Meier curve, and the survival data were compared using the log-rank test.ResultsCancer-specific survival was significantly associated with the CA repeat polymorphism, rs12423791, and rs6220 (P = 0.013, 0.014, and 0.014, respectively). Although rs7136446 had no significant association with survival, the haplotype in the LD block 3 was significantly associated with cancer-specific survival (P = 0.0003). When the sum of the risk genetic factors in each LD block (19-repeat allele, C allele of rs12423791, or C-T haplotype) was considered, patients with all the risk factors had significantly shorter cancer specific-survival than those with 0–2 risk factors (P = 0.0003).ConclusionsPolymorphisms in the IGF-1, especially a haplotype in the LD block 3, are assumed to be genetic markers predicting the outcome of metastatic PCa.

A potential association between the number of CA repeats in the promoter region of the ADAMTS9 gene with lymphatic metastasis of breast cancer

We investigated the effect of the number of cytosine-adenine (CA) repeats in the ADAMTS9 promoter region on breast cancer lymphatic metastasis. Materials and methods: Thirty-one postoperative breast cancer patients were selected and examined retrospectively. The patients were classified into 2 groups: metastatic or nonmetastatic. Thirty healthy women were selected as the control group, and their peripheral blood was obtained. Following DNA isolation from the cancer tissue specimens and peripheral blood, the promoter region of the ADAMTS9 gene was directly sequenced and the number of CA repeats was determined. Results: The number of CA repeats ranged between 19 and 21 in the control and metastatic groups. However, in the nonmetastatic group, the number of CA repeats ranged between 17 and 18. This difference in the median number of CA repeats between the control group and the nonmetastatic group was statistically significant. Conclusion: A potential relationship may exist between lymphatic metastasis in breast cancer and the number of CA repeats in the promoter region of the ADAMTS9 gene. Our study indicates a potential association between the number of CA microsatellite repeats in the promoter region of the ADAMTS9 gene and breast cancer lymphatic metastasis.

Association of a cytosine-adenine repeat polymorphism in the estrogen receptor &amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt; gene with occurrence and severity of rheumatoid arthritis

We investigated the influence of the cytosine-adenine (CA) dinucleotide repeat polymorphism in intron 6 of estrogen receptor β (ERβ) gene on rheumatoid arthritis (RA) risk. One hundred and ninety-three RA patients and 77 control subjects with osteoarthritis (OA) were recruited. The CA repeat polymorphism was assayed by a dye-terminator cycle sequencing analysis. No statistically significant difference in the mean number of CA repeats between the RA and OA patients was observed (RA: 21.47, OA: 21.23, P = 0.324). The alleles were categorized according to the number of repeats: short (S, ≦21) and long (L, ≧22), in which the genotypes SS, SL, and LL were observed. No significant differences were observed for the allele and genotype distributions of this polymorphism in both patient groups. The RA patients were classified according to RA severity: mild (least erosive disease) and severe (more erosive and mutilating disease). Again, no significant difference in genotype frequency between these groups was observed, even after stratifying by sex. The present study indicates that additional studies are needed to clarify the roles of this polymorphism, estrogen, and ER in the development of autoimmune diseases.

Insulin-like growth factor 1 gene polymorphism and breast cancer risk among arab omani women: a case-control study.

Breast cancer is the most common cancer worldwide with significant global burden. Insulin-like growth factor 1 (IGF1) is an important regulator of cellular growth, differentiation, and apoptosis and mitogenic and antiapoptotic activities. Some studies suggested an association between cytosine adenine (CA) repeats gene polymorphisms of IGF1 and the risk of developing breast cancer while other studies did not find such an association. This study aims investigate the role of IGF1 (CA) repeats gene polymorphisms in the risk of developing breast cancer among Omani women.MethodsWe analyzed (CA) repeats gene polymorphisms of IGF1 by extraction of genomic DNA from the peripheral blood of 147 patients with breast cancer and 134 control participants and performed genotyping using DNA sequencing.ResultsApproximately 46% of patients carried the IGF (CA)19 repeat allele, with 31.3% carrying two copies of this allele and 50% of controls carried the IGF (CA)19 repeat allele with 30.1% carrying two copies of this allele. The difference of the IGF CA repeat groups was significant between cases and controls with (P =0.02). In contrast, there was no difference in the distribution of (CA)19 repeat allele, (CA)18 repeat allele and (CA)19 repeat allele between cases and controls. The difference of the CA groups was significant between cases and controls among postmenopausal women with (P =0.026), whereas no difference was observed among postmenopausal subjects (P =0.429). In both pre- and postmenopausal groups there was no difference in the distribution of (CA)19 repeat allele, (CA)18 repeat allele and (CA)20 repeat allele between patients and control subjects. On further IGF1 genotypes classification, we found an association between progesterone receptor status and the genotypes group where the non carrier of (CA)19 repeat group was compared to (CA)19 repeat carrier group (OR =2.482; 95% CI =1.119–5.503; P value =0.023).ConclusionOverall there was no association between the IGF (CA)19 repeat and breast cancer in Omani females.

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

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.

Tumor hypoxia and genetic alterations in sporadic cancers

The cancer genome contains many gene alterations. How cancer cells acquire these alterations is a matter for discussion. One hypothesis is that cancer cells obtain mutations in genome stability genes at an early stage of tumor development, which results in genetic instability and generates a gene pool that enhances cellular proliferation and survival. Another hypothesis puts its emphasis on the natural selection of gene mutations for fitness. Recent data for systematic cancer genome sequencing shows that mutations in stability genes are rare in human sporadic cancers. Instead, many “passenger” mutations that do not drive the carcinogenesis process have been found in the cancer genome. Both the hypotheses mentioned above fall short in explaining recent data. Recently, many studies demonstrate the role of the tumor microenvironment, especially hypoxia and reoxygenation, in genetic instability. In this review, literature will be presented which supports a third hypothesis, i.e. that hypoxia/re-oxygenation induces genetic instability.

Di-Nucleotide Repeat Polymorphisms of the Insulin-Like Growth Factor-1 Gene and Their Association with IGF-1, Insulin-Like Growth Factor-Binding Protein-1 and Birth Size in a Sri-Lankan Cohort

Background: Insulin-like growth factor (IGF)-I is implicated in fetal growth. Ethnic variations of IGF-1 have also been suggested. Di-nucleotide repeat polymorphisms of the IGF-1 gene or their association with IGF-1 levels and birth size have not been studied in Sri Lankans. Objectives: To describe IGF-1 di-nucleotide repeat polymorphisms and their association with IGF-1 and IGF-binding protein (IGFBP)-1 levels and birth size in a cohort of Sri Lankans. Methods: A cross-sectional study on 200 mother-newborn pairs was carried out. Maternal and cord blood levels of IGF-1 and IGFBP-1 were measured by enzyme-linked immunosorbent assay. Three di-nucleotide repeat polymorphisms of the IGF-1 gene [cytosine-adenine (CA) repeats in the promoter and 3′ regions and intron 2 cytosine-thymine (CT) repeat] were studied using PCR amplification and fragment analysis. Results:Cord blood IGFBP-1 levels correlated negatively with birth weight (p < 0.01) and crown-heel length (p < 0.05). Wild-type alleles of the CA repeat polymorphisms differed from those reported in other populations. Newborn and maternal intron 2 CT repeat polymorphism showed a significant effect on birth weight (p < 0.01 and p < 0.001, respectively), crown-heel length (p < 0.01) and head circumference (p < 0.01 and p < 0.05, respectively). Promoter region CA repeat polymorphism and intron 2 CT repeat polymorphism in the newborns were significantly (p < 0.05) associated with cord blood IGF-1 levels. Almost all these effects were limited to primiparous pregnancies. Conclusions: In Sri Lankans intron 2 CT repeat polymorphism of the IGF-1 gene appears to be a significant contributor to IGF-1 levels and birth size in primiparous pregnancies.

Association of cytosine–adenine repeat polymorphism of the estrogen receptor-β gene with rheumatoid arthritis symptoms

The influence of the polymorphism of the estrogen receptor-beta gene, cytosine-adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established: <or=21 repeats (short S), >or=22 repeats (long L); and 3 kinds of genotypes (SS, SL, LL) were found. In RA patients, the L allele frequency was higher (OR = 2.03; P <or= 0.05 Fisher's test) and more subjects carried the LL genotype (OR = 5.50; P <or= 0.05 Fisher's test) compared to OA patients. It was concluded that the presence of the L allele could be a risk factor for RA, although additional larger scale study is needed.

Lung cancer susceptibility among atomic bomb survivors in relation to CA repeat number polymorphism of epidermal growth factor receptor gene and radiation dose

Lung cancer is a leading cause of cancer death worldwide. Prevention could be improved by identifying susceptible individuals as well as improving understanding of interactions between genes and etiological environmental agents, including radiation exposure. The epidermal growth factor receptor (EGFR)-signaling pathway, regulating cellular radiation sensitivity, is an oncogenic cascade involved in lung cancer, especially adenocarcinoma. The cytosine adenine (CA) repeat number polymorphism in the first intron of EGFR has been shown to be inversely correlated with EGFR production. It is hypothesized that CA repeat number may modulate individual susceptibility to lung cancer. Thus, we carried out a case-cohort study within the Japanese atomic bomb (A-bomb) survivor cohort to evaluate a possible association of CA repeat polymorphism with lung cancer risk in radiation-exposed or negligibly exposed (<5 mGy) A-bomb survivors. First, by dividing study subjects into Short and Long genotypes, defined as the summed CA repeat number of two alleles < or = 37 and > or = 38, respectively, we found that the Short genotype was significantly associated with an increased risk of lung cancer, specifically adenocarcinoma, among negligibly exposed subjects. Next, we found that prior radiation exposure significantly enhanced lung cancer risk of survivors with the Long genotype, whereas the risk for the Short genotype did not show any significant increase with radiation dose, resulting in indistinguishable risks between these genotypes at a high radiation dose. Our findings imply that the EGFR pathway plays a crucial role in assessing individual susceptibility to lung adenocarcinoma in relation to radiation exposure.

Growth Hormone Dose in Growth Hormone-Deficient Adults is Not Associated with IGF-1 Gene Polymorphisms

Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphism of the IGF-1 gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hormone (GH) treatment, resulting in different individually required GH-doses in GH-deficient patients. The aim of this study was to test if the IGF-1 gene polymorphisms are associated with the GH-dose of GH-deficient adults. A total of nine tagging SNPs, five additionally selected SNPs and a cytosine-adenine repeat polymorphism were determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years +/- 13.1 standard deviation; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. Patients received GH-treatment for 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after 1 year of treatment, IGF-1 concentrations, IGF-1-standard deviation score (SDS), the IGF-1:GH ratio and anthropometric data were analyzed by genotype. Except for rs1019731, which showed a significant difference of IGF-1-SDS by genotypes (p = 0.02), all polymorphisms showed no associations with the GH-doses, IGF-1 concentrations, IGF-1-SDS and IGF-1:GH ratio after adjusting for the confounding variables gender, age and BMI. IGF-1 gene polymorphisms were not associated with the responsiveness to exogenous GH in GHD. Therefore, genetic variations of the IGF-1 gene seem not to be major influencing factors of the GH-IGF-axis causing variable response to exogenous GH-treatment.

Analysis of cytosine adenine repeat polymorphism of the IGF-I promoter gene in children with idiopathic short stature

Purpose : A polymorphism in the IGF-I gene promoter region is known to be associated with serum IGF-I levels, birth weight, and body length, suggesting that IGF-I gene polymorphism might influence postnatal growth. The present study aimed to investigate the role of this polymorphic cytosine-adenine (CA) repeat of the IGF-I gene in children with idiopathic short stature. Methods : The study involved 131 children (72 boys and 59 girls) diagnosed with idiopathic short stature, aged 715 years. Genomic DNA was extracted from anticoagulated peripheral whole blood. The primers were designed to cover the promoter region containing the polymorphic CA repeat. Data were analyzed using GeneMapper software. The correlations between age and serum IGF-I levels were analyzed using Spearmans correlation coefficient. Results : The CA repeat sequences ranged from 15 to 22, with 19 CA repeats the most common with an allele frequency of 40.6%. Homozygous for 19 CA repeat was 13.0%, heterozygous for 19 CA repeat was 56.5%, and 19 CA non-carrier was 30.5%. The three different genotype groups showed no significant differences in height, body weight and body mass index, and serum IGF-I levels. The serum IGF-I level and age according to the IGF-I genotypes were significantly correlated in the entire group, 19 CA repeat carrier group, and the non-carrier group. The three groups also showed no significant differences in the first year responsiveness to GH treatment. Conclusion : There were no significant different correlations between 19 CA repeat polymorphism and serum IGF-I levels according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not functional in children with idiopathic short stature.

EGFR inhibition as a therapy for head and neck squamous cell carcinoma

Background: Improved understanding of disease biology of head and neck squamous cell carcinoma (HNSCC) with nearly universal expression of EGFR has led to the introduction of targeted therapies to interrupt signalling of this negative prognostic marker. Objective: We performed a literature review on the mechanisms and efficacy of anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in patients with locally advanced or recurrent/metastatic HNSCC. Results/conclusion: Clinical trials in HNSCC have administered EGFR directed drugs as single agents, in combination with chemotherapy or radiotherapy and demonstrated a good safety profile with antitumour activity in a subgroup of patients. The biology of responsiveness is still unclear, although there is growing evidence of an association of skin toxicity or presence of shorter EGFR intron 1 cytosine–adenine repeats with positive outcome.