Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children.

BACKGROUND: Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD). AIMS: To investigate whether reported genes/loci were also associated with CD in Canadian children. DESIGN AND METHODS: A case-control design was implemented at three paediatric gastroenterology clinics in Canada. Children < or =18 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in five genome-wide association studies reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. RESULTS: A total of 406 cases and 415 controls were studied. The mean (+/-s.d.) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.6%), had ileo-colonic disease (L3 +/- L4, 52.0%) and inflammatory behaviour (B1 +/- p, 86.9%) at diagnosis. Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01). Associations with SNP rs4613763 in the PTGER4 locus were marginally nonsignificant (P = 0.07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement. CONCLUSION: The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.

Interleukin 10 (IL-10) gene variants and susceptibility for paediatric onset Crohn's disease.

BACKGROUND: A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD). AIMS: To examine whether IL-10-CD associations extended to paediatric-onset CD. METHODS: We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (

Congenital anomalies in children with acute lymphoblastic leukaemia and in their family.

BACKGROUND: With the exception of Down syndrome the association between congenital anomalies and acute lymphoblastic leukaemia (ALL) is presently unclear. We investigated this association in a population-based case-control study carried out in the province of Québec, CANADA: METHODS: A total of 491 incident cases diagnosed between 1980 and 1993 and aged 0-9 years were included in the study. Healthy controls (n = 491) matched on age, sex, and region of residence at the time of diagnosis were selected from government family allowance files. Using a structured questionnaire and the International Classification of Diseases (Ninth Revision) list of congenital anomalies, presence of an anomaly was determined by interviewing the parents of the study subjects; mothers gave information on anomalies in the study subject, their siblings and her family, whereas fathers provided information on anomalies in their family. RESULTS: The adjusted risk for ALL was not increased in children who had any anomaly (odds ratio [OR] = 1.07 [95% CI : 0.70-1.65]) whereas compared to control siblings, case siblings had a higher risk of anomalies (OR = 1.54, 95% CI : 0.99- 2.42). This increase was likely due to excesses in anomalies of the heart (OR = 2.49, 95% CI : 1.23-5.04). Risk for ALL was elevated in children with a history of a congenital anomaly in their mother (OR = 1.61, 95% CI : 0.80-3.22) or her family (OR = 1.45, 95% CI : 0.94-2.25). CONCLUSIONS: Although based on small numbers for specific anomalies, these findings suggest that congenital anomalies are more prevalent in siblings and maternal family of ALL cases than in controls.

Case-control study of lung cancer among sugar cane farmers in India.

OBJECTIVES: To investigate the risk of lung cancer among sugar cane farmers and sugar mill workers. METHODS: A case-control study was conducted based in six hospitals in the predominantly sugar cane farming districts of the province of Maharashtra in India. Newly diagnosed, histologically confirmed cases were identified from these hospitals between May 1996 and April 1998. Other cancers were chosen as controls and matched to cases by age, sex, district of residence, and timing of diagnosis. RESULTS: Adjusting for confounders, an increased risk of lung cancer was found for workers ever employed on a sugar cane farm (odds ratio (OR) 1.92, 95% confidence interval (95% CI) 1.08 to 3.40). Increased risks were found for work involving preparation of the farm (OR 1.81, 95% CI 0.99 to 3.27) and burning of the farm after harvesting (OR 1.82, 95% CI 0.99 to 3.34). Non-significant increases in risks were found for harvesting the crop (OR 1.41, 95% CI 0.70 to 2.90) and processing the cane in the mills (OR 1.70, 95% CI 0.20 to 12.60). CONCLUSIONS: Exposure to fibres of biogenic amorphous silica (BAS) formed from silica absorbed from the soil and deposited in the leaves of the sugar cane crop or crystalline silica formed as a result of conversion of BAS to cristobalite at high temperatures may account for the increased risks of lung cancer among sugar cane farmers.