Is the risk of cancer increased in Asians living in the UK?

The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi) children living in the West Midlands Health Authority Region was investigated using age standardised incidence rates. Two sets of rates were calculated, a 10 year rate (1982-91) using survey based estimates of the ethnic population and a four year rate (1989-92) using the ethnic population counts from the 1991 census. The 10 year rates showed a significantly higher annual incidence of cancer in Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers in Asian children was different, with an excess of lymphomas and germ cell tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the four year rates. Although underestimation of the Asian population probably contributes to the apparent excess, there remains cause for concern that UK Asian children may be at higher risk of cancer. Accurate ethnic population figures and confirmatory studies are urgently required.     

Chronic bullous disease of childhood and a paecilomyces lung infection in chronic granulomatous disease

A 12 year old boy suffering from p67-phox deficient chronic granulomatous disease presented with a bullous skin disease and a lung infection with paecilomyces species. The histopathology of a bullous lesion showed subepidermal blister formation and microabcesses containing eosinophils in the dermal papillae. By direct immunofluorescence, linear staining of IgA at the dermal-epidermal junction was detected which confirmed the clinical diagnosis of chronic bullous disease of childhood (linear IgA dermatosis).     

Contribution of genetic and nutritional factors to DNA damage in heavy smokers

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta- carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.      

Truncal site and detoxifying enzyme polymorphisms significantly reduce time to presentation of further primary cutaneous basal cell carcinoma

Basal cell carcinoma (BCC) is the commonest cancer in Caucasians. Its incidence is rising and many patients develop multiple primary tumours at separate sites. Factors determining time between first primary tumour presentation and the next new primary lesion are unclear. We used Cox's proportional hazards model to study, in 856 Caucasians, the influence of tumour site, individual characteristics and polymorphism in glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) loci on time to next primary tumour presentation. More than one tumour at first presentation (P <0.0001, hazard ratio 2.72) and GSTT1 null (P = 0.028, hazard ratio 1.74) were associated with decreased time to next primary tumour presentation. Significant two- factor interactions, corrected for number of tumours at presentation, were identified between a truncal tumour at first presentation and each of male gender, GSTM1 null and CYP2D6 EM (P <0.003, hazard ratios 3.09- 3.82). In each of these cases, all patients with the risk combination demonstrated further separate tumours within 5 years of first presentation. Thus, patients with a truncal tumour at first presentation, especially males and those presenting with more than one lesion have a significantly decreased time to presentation of further tumours and should receive more meticulous follow-up. Polymorphism in GSTM1 and CYP2D6 also influences the rate of new primary tumour accrual giving insights into the link between ultraviolet exposure and multiple tumour development.      

Role of amylase-treated, energy-dense liquid diet in the nutritional management of acute shigellosis in children: a controlled clinical trial

To evaluate if an energy-dense porridge liquefied by amylase-rich flour (ARF) from germinated wheat increased the calorie intake in children with acute shigellosis, we studied 66 children, aged 6-35 months, in a randomized, controlled clinical trial. Children were randomized to receive either an energy-dense porridge liquefied with ARF (group 1), a thick unaltered porridge (group 2) or a porridge diluted with water (group 3) to a similar viscosity as that in group 1. MeanSD calorie intakes (kJ/kg/ day) from the porridges were 280 113, 167100 and 15180 in groups 1, 2 and 3, respectively (p = 0.006, ANOVA). Total energy intakes (meanSD) from the study diet and other food sources were 469151, 377121 and 351look J/kg/day, respectively (p = 0.006, ANOVA). Intake of breast milk was similar in all groups. Using multiple regression analysis the effect of ARF-treated energy-dense porridge in increasing the calorie intake persisted after adjusting for a number of confounders, such as age of the child, isolation of Shigella dysenteriae type 1 and fever. The results of this study suggest that ARF-treated porridge increases energy intake in infants and young children during acute shigellosis. This feeding approach may be useful in preventing malnutrition following dysentery due to shigellosis. Amylase, energy-dense, energy intake, liquefied, shigellosis
D Mahalanabis, Clinical Sciences Division, International Centre for Diarrhoeal Disease Research, GPO Box 128, Dhaka 1000, Bangladesh     

The survival motor neuron protein in spinal muscular atrophy

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non- SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.      

Evaluating patients with renal failure for renal artery stenosis with gadolinium-enhanced magnetic resonance angiography

The incidence and prevalence of end-stage renal disease (ESRD) continues to increase, especially in the elderly population. The role of renovascular disease in contributing to ESRD is still not well defined. The objective of this study was to determine the utility of gadolinium (Gd)-enhanced magnetic resonance angiography (MRA) in evaluating elderly patients with renal insufficiency for renal artery stenosis (RAS). A 7-month prospective study conducted in a tertiary referral center evaluated 40 consecutive patients with progressive renal insufficiency (18 men and 22 women; mean age, 70 +/- 5.6 [standard deviation] years) and high clinical suspicion for renovascular disease with Gd-enhanced MRA. Digital subtraction angiography (DSA) was obtained in only those patients with significant RAS detected by MRA. Twelve patients had significant RAS. Six of these patients had percutaneous transluminal renal angioplasty (PTRA), five patients had renal artery bypass surgery, and one patient had a stent placed after PTRA. Seventy-eight renal arteries were satisfactorily evaluated by MRA. Twenty-two renal arteries were evaluated by both MRA and DSA. Of the 12 significant stenoses detected by the MRA, 11 were confirmed by DSA and 1 was confirmed at the time of surgical revascularization. It is concluded that Gd-enhanced MRA is a useful test for the evaluation of RAS in patients with compromised renal function.