Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.     

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.     

Epithelial advanced ovarian carcinoma in the central region of Tunisia: therapeutic results and prognostic factors on 104 patients

Between 1994 and 2004, 104 patients with epithelial advanced ovarian cancer were treated in the central region of Tunisia (81 stage III and 23 stage IV). Average age of patients was 54 years. Primary surgery was optimal (residue < 2 cm) in 40 cases (38,5 % of patients). Fifty nine patients were treated with neo adjuvant chemotherapy based on platinum, associated to paclitaxel in 19 % of cases. Interval debulking surgery interested 30 patients and was optimal in 66,7 % of cases. Global survive was 57 % at 2 years and 27 % at 5 years. Survival rate for patients treated with optimal debulking surgery was similar to that of those treated with initial optimal surgery. Prognostic factors for a better survive were : age < 40 years (p < 0,05), stage III (p < 0,01), a normal level of CA125 after surgery (p < 0,01), primary optimal initial surgery (p < 0,02) and response to neoadjuvant chemotherapy (p < 0,01). Prognosis of ovarian carcinoma is worse in Tunisia as like as in the world. In case of extensive tumor, the neoadjuvant chemotherapy before interval debulking surgery permits to improve survive and quality of life in some patients.     

Filiation hamartoma polyposis dysplasia and small bowel adenocarcinoma

Peutz-Jeghers syndrome is a hereditary affection with dominant autosomal transmission. The risk of cancerisation is largely higher than that in the general population. Dysplasia is rare. Transformation of the polyposis hamartoma into a site of dysplasia then into adenocarcinoma has been rarely reported. The authors report the case of a 14 year-old patient, having a severe dysplasia on ileal polyposis hamartoma related to the syndrome of Peutz-Jeghers.     

Factors influencing homocysteineamia in type 2 diabetic patients

Previous studies have suggested that hyperhomocysteinaemia (Hcy) could be a strong and independent cardiovascular risk factor. Many factors could influence the serum concentration of Hcy such as vitamin B 12, folic acid, renal failure, hypothyroid status, ovarian failure and cancers. So the aim of our study was to evaluate the prevalence of hyperhomocysteinaemia among 54 type 2 diabetic patients and to study, its relationship with vitamin B12, folic acid and Metformin. Were excluded all patients with an evident cause of hyperhomocysteinaemia. Mean age of patients was 52.8 years. Mean Hcy was 11.7 + 6.9 micromol/l. The prevalence of hyperhomocysteinaemia was 27.8% in our group. There were eight (14%) patients with vitamin B12 deficiency and three among them had hyperhomocysteinaemia. There was no folic acid deficiency and no relationship with Metformin treatment. We suggest a wide screening of hyperhomocysteinaemia in type 2 diabetic patients and folic acid or vitamin B12 supplements if necessary.     

11 beta hydroxylase deficiency: a clinical study of seven cases

11 beta-hydroxylase deficiency is a rare recessive autosomal disorder. The aim of this report was to describe among a retrospective study of seven cases, different clinical pictures, problems in diagnosis and management. Results: the frequency of 11 beta-hydroxylase deficiency was 17.5% of congenital adrenal hypererplasia etiology in our study. Consanguinity was found in all cases. The sex ratio was 5 boys/2 girls. Median age on diagnosis was 4.3 years. Five cases were revealed with precocious puberty associated with hypertension. One patient had sexual ambiguity, Prader IV stage, hypertension appears later. One patient developed heterosexual precocious puberty and hypertension at five years of age. One patient had bilateral testicular adrenal rests. Hypertension was diagnosed early in 4 cases and secondarly in the other 3 cases. Hypertension was severe complicated by convulsions, facial paralysis and epistaxis. Hypo kaliemia was identified in six cases. Hormonal investigations confirmed diagnosis in all cases. The secondary sexual characteristics were controled by glucocorticoid substitution. Antihypertensive treatment was necessary initially and prolonged only in three cases. Prognosis of final height of patients with late diagnosis was particularly compromised.     

Pulmonary inflammatory pseudotumor: difficulties in diagnosis and prognosis

Inflammatory pseudotumors are uncommon benign lesions of the lung of unknown origin, that may show aggressive behavior. Although pseudotumors constitute less than 1% of all lung tumors, they are reported to be the most common cause of solitary lung masses in children. Complete resection, when possible, is safe and leads to excellent survival. The case presented here highlights difficulties in clinical and histologic diagnosis.     

Frequency and clinical significance of core promoter and precore region mutations in Tunisian patients infected chronically with hepatitis B

Genetic variability of hepatitis B virus (HBV) in the C gene and its association with the different stages of chronic liver disease has been studied inadequately with controversial results. The objectives of the current study were to determine the frequency of core promoter and precore mutations in chronic hepatitis B in Tunisia and to evaluate their impact on viral replication and disease progression. Sequencing was performed in upstream regulatory sequence (URS), pre‐core (PreC) and basal core promoter (BCP) regions for 123 chronic infected patients by HBV genotype D at different status of disease. Mutations were detected in 98.4% of cases, affecting URS, BCP and Pre‐C in 95.1%, 95.9% and 87.8% respectively. Multi‐mutations increased significantly from asymptomatic carrier to advanced liver disease status. G1896A (74.8%), G1764A/T/C (71.5%), G1899A (54.4%) and T1678C (52%) were the most common. Special attention should be paid to A1703T, T1678C/G‐A1703T, and A1652G‐A1679G mutations probably specific of Tunisians sequences; they were observed in 40.6%, 41.5% and 30.1% respectively. A1679G/C, T1753C/G/A, A1762T/G and A1762T‐G1764A were more prevalent in older patients. High DNA levels were associated with G1899A or G1764T/C‐C1766G‐C1799G and advanced liver disease with mutations at positions 1762, 1764 and/or 1899 alone or in double or triple mutations. It was also shown that substitutions at nucleotides 1762, 1764 and 1899 have an impact on the disease progression. It is the first report for specific mutations in the URS region for genotype D. It should be completed by studying eventual correlation with clinical progression and the response to treatment. J. Med. Virol. 84:1719–1726, 2012. © 2012 Wiley Periodicals, Inc.     

Role of Helicobacter pylori infection in iron deficiency anemia

Anemia induced by digestive diseases refers to anemia due to iron deficiency. Conventional gastrointestinal diagnostic workup fails to establish the cause of iron deficiency in about one third of patients. Abnormal iron absorption is increasingly recognized as an important cause of unexplained iron deficiency. The importance of coeliac disease as a possible cause of iron deficiency anemia refractory to oral iron treatment, without other manifestations of malabsorption syndrome, is increasingly being recognized. In addition, Helicobacter pylori (HP) has been implicated in several recent studies as a cause of iron deficiency anemia (IDA) refractory to oral iron treatment. Cure of previously refractory IDA by HP eradication provides strong evidence supporting a cause-and-effect relationship. In order to establish a cause-and-effect relationship between HP gastritis and IDA, prospective randomized studies comparing the effects of iron administration with or without H. pylorieradication are highly recommended.     

Rituximab in rheumatoid arthritis and the risk of malignancies: report from a French cohort

Objective

To determine in real-life conditions the safety of treatment with rituximab (RTX) in patients with rheumatoid arthritis (RA) regarding malignancies.

Methods

Analysis of safety data from a cohort of RA patients who received at least one course of RTX. RA patients with previous malignancies were followed-up and compared to the group of patients with no history of malignancy.

Results

One hundred and eighty-six RA patients, 33 (17.7%) males, the mean age and disease duration were 55.8 ± 13.0 and 14.5 ± 11.1 years, respectively. The mean follow-up was 22.3 ± 15.1 months, corresponding to a follow-up of 346 pt-years of RTX exposure. Among these, 24 (12.9%) patients had a history of a prior malignancy. Five cancers were diagnosed during follow-up with four new malignancies (1 prostate, 1 breast, 1 colon and 1 cervical cancers) and one recurrence of a known breast cancer. The overall cancer rate was 1.45/100 pt-years (95%CI: 0.19 to 2.70), which is comparable to previously studied DMARD-treated cohorts. No new hematopoietic neoplasms were reported and the six lymphomas that have been in remission prior to RTX-therapy remained under follow-up. The baseline demographic and disease characteristics and the cancer-risk of the 24 patients who presented with a prior malignancy were similar to those with no cancer history (162 patients).

Conclusions

Although based on a modest number of observed cancers, and despite selection bias (12.9% of prior malignancies in our RTX treated RA), this observational study suggests that RTX does not increase the cancer risk in RA patients.