Modeling Gene-Environment Interaction for the Risk of Non-hodgkin Lymphoma.

Background: Non-hodgkin lymphoma (NHL) is one of the most common and deadly cancers. There is limited analysis of gene-environment interactions for the risk of NHL. This study intends to explore the interactions between genetic variants and environmental factors, and how they contribute to NHL risk. Methods: A case-control study was performed in Shanghai, China. The cases were diagnosed between 2003 and 2008 with patients aged 18 years or older. Samples and SNPs which did not satisfy quality control were excluded from the analysis. Weighted and unweighted genetic risk scores (GRS) and environmental risk scores were generated using clustering analysis algorithm. Univariate and multivariable logistic regression analyses were conducted. Moreover, genetics and environment interactions (G × E) were tested on the NHL cases and controls. Results: After quality control, there are 22 SNPs, 11 environmental variables and 5 demographical variables to be explored. For logistic regression analyses, 5 SNPs (rs1800893, rs4251961, rs1800630, rs13306698, rs1799931) and environmental tobacco smoking showed statistically significant associations with the risk of NHL. Odds ratio (OR) and 95% confidence interval (CI) was 10.82 (4.34-28.88) for rs13306698, 2.84 (1.66-4.95) for rs1800893, and 2.54 (1.43-4.58) for rs4251961. For G × E analysis, the interaction between smoking and dichotomized weighted GRS showed statistically significant association with NHL (OR = 0.23, 95% CI = [0.09, 0.61]). Conclusions: Several genetic and environmental risk factors and their interactions associated with the risk of NHL have been identified. Replication in other cohorts is needed to validate the results.

Associations between genetic variants in immunoregulatory genes and risk of non-Hodgkin lymphoma in a Chinese population.

We undertook a hospital-based case-control study to examine the associations between single nucleotide polymorphisms (SNPs) in selected immunoregulatory genes and non-Hodgkin lymphoma (NHL) risk in a Chinese population. One hundred and sixty-nine NHL patients diagnosed according to the World Health Organization (WHO) 2001 standard and 421 controls were recruited. Nine SNPs in three genes (IL-10, IL-1RN, and TNF-α) were selected based on predicted functions and previous study findings. Genetic association analysis was performed using the Cochran-Armitage trend test and multiple logistic regression. Four SNPs were associated with an increased risk of overall NHL: odds ratio per minor allele [ORper-minor-allele] and 95% confidence interval [CI] were 2.64 (1.75-3.98) for IL-10 rs1800893, 2.67 (1.72-4.16) for IL-1RN rs4251961, 1.80 (1.24-2.63) for TNF- α rs1800630, and 1.55 (1.02-2.37) for TNF- α rs2229094. These SNPs were also associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In addition, another SNP (TNF- α rs1041981) was associated with an increased risk of DLBCL (ORper-minor-allele=1.73, 95% CI 1.14-2.61). The findings provide evidence on the role of these immunoregulatory gene variants in NHL etiology.

[Contribution of environmental lead exposure to blood lead level among infants based on IEUBK model].

OBJECTIVE: To evaluate the influence of environmental lead exposure on infant's blood lead through integrated exposure uptake biokinetic model for lead in children (IEUBK) model, based on environmental lead and prenatal lead exposure. METHODS: The data is from a prospective study conducted among pregnant women during 2005 -2007. Blood lead of the pregnant women in the late pregnancy, environmental lead values including lead concentration in soil, air and drink-water were measured. Moreover, the blood lead concentrations of infants were measured as well. RESULTS: Infants were exposed to lead from the pregnant women during the pregnancy, and in the late pregnancy the geometric mean blood lead of pregnant women was (40.3 +/- 3.7) microg/L. The geometric mean blood lead concentration of six-month old infants was (54.7 +/- 6.7) microg/L and there were 17.3% infants whose blood lead concentration were above 100 microg/L. Lead in soil,atmosphere and drink-water were 45.57 mg/kg, 0.023 microg/m3 and 3.25 microg/L respectively. While based on the calculation of the IEUBK model, the value attributed to environmental lead exposure was 12.4 microg/L, accounting for 22.7% of the real blood lead level. CONCLUSION: The results indicated that environmental lead contamination in the rural area might not be the main reason of elevation in blood lead among infants, other lead resources such as food lead exposure might be the major sources for the intake of lead among infants and should be paid more attentions in future.

Case-control study of risk factors of myelodysplastic syndromes according to World Health Organization classification in a Chinese population.

Risk factors of mydelodysplastic syndromes (MDS) remain largely unknown. We conducted a hospital-based case-control study consisting of 403 newly diagnosed MDS patients according to World Health Organization classification and 806 individually gender and age-matched patient controls from 27 major hospitals in Shanghai, China, to examine relation of lifestyle, environmental, and occupational factors to risk of MDS. The study showed that all MDS (all subtypes combined) risk factors included anti tuberculosis drugs [odds ratio (OR)(adj) = 3.15; 95% confidence interval (CI) = 1.22-8.12] as an independent risk factor, benzene (OR(adj) = 3.73; 95% CI = 1.32-10.51), hair dye use (OR = 1.46; 95% CI = 1.03-2.07), new building and renovations (OR = 1.69; 95% CI = 1.11-2.00), pesticides (OR = 2.16; 95% CI = 1.22-3.82), and herbicides (OR = 5.33; 95% CI = 1.41-20.10) as relative risk factors. Risk factors of MDS subtype refractory cytopenia with multiple dysplasia (RCMD) were benzene (OR(adj) = 5.99; 95% CI = 1.19-30.16) and gasoline (OR(adj) = 11.44; 95% CI = 1.31-100.03) as independent risk factors, and traditional Chinese medicines (OR = 2.17; 95% CI = 1.15-4.07), pesticides (OR = 2.92; 95% CI = 1.37-6.25), and herbicides (OR = 12.00; 95% CI = 1.44-99.67) as relative risk factors. Smoking tobacco was significantly associated with refractory anemia with excess of blasts (RAEB) (OR(adj) = 2.43; 95% CI = 1.02-5.77). Education is shown as an independent protective factor against all MDS (OR(adj) = 0.90; 95% CI = 0.83-0.99) and RCMD (OR(adj) = 0.89; 95% CI = 0.79-0.99). These findings suggest that multiple modifiable behavioral, environmental, and occupational factors play a role in MDS etiology, and various MDS subtypes may have different susceptibility.

Combined 677CC/1298AC genotypes of methylenetetrahydrofolate reductase (MTHFR ) reduce susceptibility to precursor B lymphoblastic leukemia in a Chinese population.

The methylenetetrahydrofolate reductase (MTHFR) encodes a major enzyme in folate metabolism. It has been suggested that two MTHFR polymorphisms, 677C>T and 1298A>C, influence risk of acute lymphoblastic leukemia (ALL). Most studies on relation of MTHFR polymorphisms to ALL susceptibility have been in pediatric populations because ALL is relatively rare in adults. Here, we report a case-control study of 127 Chinese patients with adult precursor B lymphoblastic leukemia (B-ALL) to examine correlation between the MTHFR polymorphisms and B-ALL susceptibility in adults. Our data show that although the prevalence of genotype 1298CC was significantly higher in the female patients than in the controls (P = 0.04), the differences in distributions of combined genotypes of 1298CC with either 677CC or 677CT between the cases and the controls were statistically insignificant. Haplotype analysis revealed no significant difference between the cases and the controls. The prevalence for joint MTHFR genotypes 677CC/1298AC was significantly lower in the female B-ALL cases than in the controls [odds ratio (OR) = 0.06, 95% CI = 0.00-0.53, P = 0.0033] and no differences among the men [OR = 0.71, 95% CI = 0.20-2.53, P = 0.55], suggesting that protective effects of combined MTHFR 677CC/1298AC genotypes on susceptibility of adult B-ALL are gender bias toward women with 677CC/1298AC women being at a 17-fold reduced odds to develop B-ALL.