Delayed infection, late tonsillectomy or adenoidectomy and adult leukaemia: a case-control study.

In a population-based case-control study among adults in Italy, of 261 lymphoid and 313 myeloid leukaemias and 1718 controls, a later age at adenoidectomy and tonsillectomy (after age 10 years) increased considerably the risk of lymphocytic (but not myeloid) leukaemia (odds ratio 4.2, 95% confidence interval 1.1-16.2). We propose that late infection is a proliferative stimulus for B-cells.

DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study.

Individuals differ widely in their ability to repair DNA damage, and DNA-repair deficiency may be involved in modulating cancer risk. In a case-control study of 124 bladder-cancer patients and 85 hospital controls (urological and non-urological), 3 DNA polymorphisms localized in 3 genes of different repair pathways (XRCC1-Arg399Gln, exon 10; XRCC3-Thr241Met, exon 7; XPD-Lys751Gln, exon 23) have been analyzed. Results were correlated with DNA damage measured as (32)P-post-labeling bulky DNA adducts in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis, and allele frequencies in cases/controls were as follows: XRCC1-399Gln = 0.34/0.39, XRCC3-241Met = 0.48/0.35 and XPD-751Gln = 0.42/0.42. Odds ratios (ORs) were significantly greater than 1 only for the XRCC3 (exon 7) variant, and they were consistent across the 2 control groups. XPD and XRCC1 appear to have no impact on the risk of bladder cancer. Indeed, the effect of XRCC3 was more evident in non-smokers [OR = 4.8, 95% confidence interval (CI) 1.1-21.2]. XRCC3 apparently interacted with the N-acetyltransferase type 2 (NAT-2) genotype. The effect of XRCC3 was limited to the NAT-2 slow genotype (OR = 3.4, 95% CI 1.5-7.9), suggesting that XRCC3 might be involved in a common repair pathway of bulky DNA adducts. In addition, the risk of having DNA adduct levels above the median was higher in NAT-2 slow acetylators, homozygotes for the XRCC3-241Met variant allele (OR = 14.6, 95% CI 1.5-138). However, any discussion of interactions should be considered preliminary because of the small numbers involved. Our results suggest that bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA cross-link lesions produced by aromatic amines and other environmental chemicals.

Chromosome 8, occupational exposures, smoking, and acute nonlymphocytic leukemias: a population-based study.

In a previous epidemiological study on acute myelocytic leukemia (M. M. Crane et al., Cancer Epidemiol. Biomark. Prev., 5: 639-644, 1996), clonal aberrations in chromosome 8 have been reported to be in excess in smokers and in workers exposed to paints. In that study, cytogenetics was performed after therapy. In our report, we describe a population-based survey on nonlymphocytic leukemias in northern Italy, in which 79 patients (acute myelocytic leukemia, myelodysplastic syndromes, or other nonlymphocytic leukemias) were studied before cytotoxic therapy. We found 9 aberrations involving chromosome 8 (six +8, two -8, and one translocation), whereas abnormalities involving chromosomes 5 and 7 occurred with a low frequency compared with previous studies. Aberrations involving chromosome 8 were associated with smoking (odds ratio, 6.3; 95% confidence interval, 0.9-42.3; among smokers of 10 or more cigarettes/day: odds ratio, 14.2; 95% confidence interval, 1.4-142.3); +8 aberrations were found in 1 of 24 nonsmokers and in 5 of 38 smokers. Three +8 aberrations were found in 22 subjects potentially exposed to solvents or polycyclic aromatic hydrocarbons. The low frequency of chromosome 5 and 7 aberrations in our population-based series (compared with other studies) can be attributed to the recruitment before cytotoxic therapies. Aberrations involving chromosome 8 (particularly +8) were associated with smoking habits. Chromosome 8 includes the c-myc oncogene.

Myeloid leukemias and myelodysplastic syndromes: chemical exposure, histologic subtype and cytogenetics in a case-control study.

We conducted a case control study of 50 acute myeloid leukemias (AML), 17 chronic myeloid leukemias (CML), 19 myelodysplastic syndromes (MDS), and 246 controls. The cases were classified according to the French-American-British (FAB) classification, and chromosome aberrations were recorded according to the International System for Human Cytogenetic Nomenclature. Exposure to suspected leukemogenic agents was assessed blindly by an industrial hygienist. Increased risks were noted for mechanics, welders, electricians, and drivers among men and among farmers and textile workers among women. Increased SMRs for leukemias in a census-based cohort study conducted in the same area (Torino) were previously reported for electricians and drivers among men and for textile workers among women. We detected nonstatistically significant increased relative risks for exposure to benzene (odds ratio, OR = 1.7), petrol refining products (1.9), polycyclic aromatic hydrocarbons (1.7), and electromagnetic fields (1.6) in men; in women, a statistically significant association with exposure to pesticides was detected [OR = 4.4; 95% confidence interval (CI) 1.7-11.5]. Although exposure to pesticides was confined to AML, MDS cases included a high proportion of subjects exposed to benzene and electromagnetic fields. No particular histologic subtype of AML was associated with chemical exposures except for that of pesticides with the M4 category. Chromosome aberrations were not associated with chemical exposures (OR = 1.0), but a nonstatistically significant excess was noted in association with electromagnetic fields (OR = 2.1).