Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P ¼ 10 À10 and 10 À9 , respectively). These effects became more apparent with increasing alcohol consumption (P for trend ¼ 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.The alcohol dehydrogenase (ADH) pathway includes seven distinct ADH genes, a key candidate gene group for aerodigestive cancers 1-3 .Studies of aerodigestive cancer in populations of European origin have focused on ADH1C with little evidence of any effect 4 . We previously reported an association for ADH1B R48H (rs1229984) in a central European (CE) population 5 and now consider the effect of this and five other ADH variants in an expanded study comprising 809 aerodigestive cancer cases and 2,586 controls from the CE study as well as a further 3,067 aerodigestive cancer cases and 2,692 controls from two other studies in Europe (ARCAGE study) and Latin America (LA study) (total of 3,876 cases and 5,278 controls). All three studies were coordinated by the International Agency for Research on Cancer (IARC) and followed a similar protocol (Supplementary Methods online). Of the 3,876 cases, 1,790 were cancers of the oral cavity or pharynx, 1,659 were cancers of the hypopharynx or larynx and 427 were cancers of the esophagus (Supplementary Table 1 online). Cases with a histology other than squamous cell were excluded.The HapMap Consortium has genotyped 163 SNPs in the vicinity of the ADH gene cluster with a minor allele frequency (MAF) of 4% or more in the CEPH Utah (CEU) population 6 . Inspection of the linkage disequilibrium (LD) pattern across this region indicates that ADH1A, ADH1B, ADH1C, ADH4, ADH5 and ADH6 are relatively highly correlated, whereas ADH7 showed little correlation with the remaining six ( Supplementary Fig. 1a online). From all verified missense SNPs in the seven ADH genes found in both the NCBI SNP and SNP500 databases 7 , we selected eight that had a MAF 4 4% in the CEU population. Three missense SNPs in ADH4 (rs1126671, rs1126673 and rs1042364) were in strong LD, and thus were genotyped by the highly correlated tagging SNP rs1984362 (r 2 4 0.89). In total, we genotyped six genetic variants (five missense SNPs and one tagging SNP) in all three studies (Table 1 and Supplementary Table 2 online).In the pooled analysis on all 3,876 cases and 5,278 controls, four variants reported a significant association (Supplementary Table 3 online). The most prominent was with rs1229984 (in ADH1B; OR for codominant model ¼ 0.59 (95% CI ¼ 0.50-0.69); P under codominant model ¼ 8 Â 10 À10 ). This variant w...

No abstract

Child labor remains a widespread problem. Although it can have positive effects, in some situations it has negative effects on health and development of the children. Although mainly a problem in developing countries, it is also possible to find child workers, some working in hazardous activities, in developed countries. The authors describe the child labor profiles in developed and developing countries, the principal occupations of children, and their concomitant hazards. They summarize the epidemiologic evidence for a greater impact of some occupational exposures on the health of children as compared with adults, and the theoretical concerns about the impact of child labor on health, and suggest policies that can be used to combat harmful child labor.

SYNOPSISObjectives. This article describes the prevalence of musculoskeletal pain in several anatomic sites in children and teens, and investigates, while adjusting for potential confounders, the association between musculoskeletal pain and back pain and the following: age, gender, sports practice, use of computer/video games/television, school attendance, intensity of involvement in household domestic activities, care of other children, care of sick/elderly family members, work activities, and workloads.Methods. We conducted a cross-sectional study interviewing 3,269 children aged 10-17 years in the low-income areas of Pelotas, Brazil.Results. The prevalence of pain in the neck, knee, wrist or hands, and upper back exceeded 15%. Workers in manufacturing had a significantly increased risk for musculoskeletal pain (prevalence ratio [PR]ϭ1.31) and for back pain (PRϭ1.69), while workers in domestic service had 17% more musculoskeletal pain and 23% more back pain than nonworkers. Awkward posture (PRϭ1.15) and heavy physical work (PRϭ1.07) were associated with musculoskeletal pain, while monotonous work (PRϭ1.34), awkward posture (PRϭ1.31), and noise (PRϭ1.25) were associated with back pain.Conclusions. Musculoskeletal pain is common among working children and teens. Knowledge of occupational risk factors can support actions to restructure work conditions to reduce or eliminate childhood exposure to hazardous conditions. Our results suggest that strategies to prevent musculoskeletal disorders in child workers should be developed.

Our results reinforce the need for respecting the minimum age for admission to employment established by the ILO Convention 138 and by the Brazilian legislation and contribute to the discussion about the occupations that should be considered as hazardous child labour.