The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed.

Determining disease prevalence from incidence and survival using simulation techniques.

OBJECTIVES: We present a new method for determining prevalence estimates together with estimates of their precision, from incidence and survival data using Monte-Carlo simulation techniques. The algorithm also provides for the incidence process to be marked with the values of subject level covariates, facilitating calculation of the distribution of these variables in prevalent cases. METHODS: Disease incidence is modelled as a marked stochastic process and simulations are made from this process. For each simulated incident case, the probability of remaining in the prevalent sub-population is calculated from bootstrapped survival curves. This algorithm is used to determine the distribution of prevalence estimates and of the ancillary data associated with the marks of the incidence process. This is then used to determine prevalence estimates and estimates of the precision of these estimates, together with estimates of the distribution of ancillary variables in the prevalent sub-population. This technique is illustrated by determining the prevalence of acute myeloid leukaemia from data held in the Haematological Malignancy Research Network (HMRN). In addition, the precision of these estimates is determined and the age distribution of prevalent cases diagnosed within twenty years of the prevalence index date is calculated. CONCLUSION: Determining prevalence estimates by using Monte-Carlo simulation techniques provides a means of calculation more flexible that traditional techniques. In addition to automatically providing precision estimates for the prevalence estimates, the distribution of any measured subject level variables can be calculated for the prevalent sub-population. Temporal changes in incidence and in survival offer no difficulties for the method.

Melanocortin 1 receptor (MC1R), pigmentary characteristics and sun exposure: findings from a case-control study of diffuse large B-cell and follicular lymphoma.

The relationship between skin cancer and non-Hodgkin lymphoma (NHL) suggests common genetic, host or environmental causes. Ultraviolet radiation (UVR), pigmentary characteristics have been linked with both malignancies, and for skin cancer, the melanocortin 1 receptor (MC1R) which influences pigmentation has also been implicated. This paper reports on the relationship between MC1R, skin, hair and eye colour, time spent outdoors, and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Persons carrying MC1R homozygote variant alleles at R151C, R160W, D294H and D84E were more likely to have fair skin, red hair and to spend less time outdoors than those who did not. The variant allele at V92M was associated with FL (odds ratio (OR)=1.61, 95% confidence interval (CI) 1.08-2.39) and the r:wild type genotype with DLBCL (OR=0.58, 95% CI 0.38-0.89). Interactions between MC1R genotypes and skin colour influenced DLBCL risk; the RR genotype increased risk in individuals with medium or dark skin, based on 5 cases and no controls, but decreased risk among those of fair skin. On the whole, DLBCL and FL risk were not related to genetic variation in MC1R, pigmentation or time spent outdoors.

Genetic variation in the folate metabolic pathway and risk of childhood leukemia.

Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C>T, MTHFR 1298 A>C, SHMT1 1420 C>T, MTR 2756 A>G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development.