Association between xenobiotic gene polymorphisms and non-Hodgkin's lymphoma risk

The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively. Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR = 4.27; 95% CI, 2.40-7.61, P < 0.001) and PON1 BB a 2.9-fold increase (OR = 2.92; 95% CI, 1.49-5.72, P = 0.002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.

Clinical and radiographic outcomes of acetabular impaction grafting without cage reinforcement for revision hip replacement : a minimum ten-year follow-up study

Impaction bone grafting for reconstitution of bone stock in revision hip surgery has been used for nearly 30 years. We used this technique, in combination with a cemented acetabular component, in the acetabula of 304 hips in 292 patients revised for aseptic loosening between 1995 and 2001. The only additional supports used were stainless steel meshes placed against the medial wall or laterally around the acetabular rim to contain the graft. All Paprosky grades of defect were included. Clinical and radiographic outcomes were collected in surviving patients at a minimum of 10 years following the index operation. Mean follow-up was 12.4 years (SD 1.5; range 10.0-16.0). Kaplan-Meier survivorship with revision for aseptic loosening as the endpoint was 85.9% (95% CI 81.0 to 90.8%) at 13.5 years. Clinical scores for pain relief remained satisfactory, and there was no difference in clinical scores between cups that appeared stable and those that appeared loose radiographically.

The impact of heatwaves on mortality and emergency hospital admissions from non-external causes in Brisbane, Australia

Objectives Heatwaves can have significant health consequences resulting in increased mortality and morbidity. However, their impact on people living in tropical/subtropical regions remains largely unknown. This study assessed the impact of heatwaves on mortality and emergency hospital admissions (EHAs) from non-external causes (NEC) in Brisbane, a subtropical city in Australia. Methods We acquired daily data on weather, air pollution and EHAs for patients aged 15 years and over in Brisbane between January 1996 and December 2005, and on mortality between January 1996 and November 2004. A locally derived definition of heatwave (daily maximum ≥37°C for 2 or more consecutive days) was adopted. Case–crossover analyses were used to assess the impact of heatwaves on cause-specific mortality and EHAs. Results During heatwaves, there was a statistically significant increase in NEC mortality (OR 1.46; 95% CI 1.21 to 1.77), cardiovascular mortality (OR 1.89; 95% CI 1.44 to 2.48), diabetes mortality in those aged 75+ (OR 9.96; 95% CI 1.02 to 96.85), NEC EHAs (OR 1.15; 95% CI 1.07 to 1.23) and EHAs from renal diseases (OR 1.41; 95% CI 1.09 to 1.83). The elderly were found to be particularly vulnerable to heatwaves (eg, for NEC EHAs, OR 1.24 for 65–74-year-olds and 1.39 for those aged 75+). Conclusions Significant increases in NEC mortality and EHAs were observed during heatwaves in Brisbane where people are well accustomed to hot summer weather. The most vulnerable were the elderly and people with cardiovascular, renal or diabetic disease.

The impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy on survival in patients with a history of breast cancer – a population-based data linkage study

Prophylactic surgery including hysterectomy and bilateral salpingo-oophorectomy (BSO) is recommended in BRCA positive women, while in women from the general population, hysterectomy plus BSO may increase the risk of overall mortality. The effect of hysterectomy plus BSO on women previously diagnosed with breast cancer is unknown. We used data from a population-base data linkage study of all women diagnosed with primary breast cancer in Queensland, Australia between 1997 and 2008 (n=21,067). We fitted flexible parametric breast cancer specific and overall survival models with 95% confidence intervals (also known as Royston-Parmar models) to assess the impact of risk-reducing surgery (removal of uterus, one or both ovaries). We also stratified analyses by age 20-49 and 50-79 years, respectively. Overall, 1,426 women (7%) underwent risk-reducing surgery (13% of premenopausal women and 3% of postmenopausal women). No women who had risk-reducing surgery, compared to 171 who did not have risk-reducing surgery developed a gynaecological cancer. Overall, 3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy plus BSO was associated with significantly reduced risk of death overall (adjusted HR = 0.69, 95% CI 0.53-0.89; P =0.005). Risk reduction was greater among premenopausal women, whose risk of death halved (HR, 0.45; 95% CI, 0.25-0.79; P < 0.006). This was largely driven by reduction in breast cancer-specific mortality (HR, 0.43; 95% CI, 0.24-0.79; P < 0.006). This population-based study found that risk-reducing surgery halved the mortality risk for premenopausal breast cancer patients. Replication of our results in independent cohorts, and subsequently randomised trials are needed to confirm these findings.

Impact of climate variability on Plasmodium vivax and Plasmodium falciparum malaria in Yunnan Province, China

BACKGROUND Malaria remains a public health problem in the remote and poor area of Yunnan Province, China. Yunnan faces an increasing risk of imported malaria infections from Mekong river neighboring countries. This study aimed to identify the high risk area of malaria transmission in Yunnan Province, and to estimate the effects of climatic variability on the transmission of Plasmodium vivax and Plasmodium falciparum in the identified area. METHODS We identified spatial clusters of malaria cases using spatial cluster analysis at a county level in Yunnan Province, 2005-2010, and estimated the weekly effects of climatic factors on P. vivax and P. falciparum based on a dataset of daily malaria cases and climatic variables. A distributed lag nonlinear model was used to estimate the impact of temperature, relative humidity and rainfall up to 10-week lags on both types of malaria parasite after adjusting for seasonal and long-term effects. RESULTS The primary cluster area was identified along the China-Myanmar border in western Yunnan. A 1°C increase in minimum temperature was associated with a lag 4 to 9 weeks relative risk (RR), with the highest effect at lag 7 weeks for P. vivax (RR = 1.03; 95% CI, 1.01, 1.05) and 6 weeks for P. falciparum (RR = 1.07; 95% CI, 1.04, 1.11); a 10-mm increment in rainfall was associated with RRs of lags 2-4 weeks and 9-10 weeks, with the highest effect at 3 weeks for both P. vivax (RR = 1.03; 95% CI, 1.01, 1.04) and P. falciparum (RR = 1.04; 95% CI, 1.01, 1.06); and the RRs with a 10% rise in relative humidity were significant from lag 3 to 8 weeks with the highest RR of 1.24 (95% CI, 1.10, 1.41) for P. vivax at 5-week lag. CONCLUSIONS Our findings suggest that the China-Myanmar border is a high risk area for malaria transmission. Climatic factors appeared to be among major determinants of malaria transmission in this area. The estimated lag effects for the association between temperature and malaria are consistent with the life cycles of both mosquito vector and malaria parasite. These findings will be useful for malaria surveillance-response systems in the Mekong river region.

Air pollution, temperature and pediatric influenza in Brisbane, Australia

Previous studies have demonstrated the importance of weather variables in influencing the incidence of influenza. However, the role of air pollution is often ignored in identifying the environmental drivers of influenza. This research aims to examine the impacts of air pollutants and temperature on the incidence of pediatric influenza in Brisbane, Australia. Lab-confirmed daily data on influenza counts among children aged 0-14years in Brisbane from 2001 January 1st to 2008 December 31st were retrieved from Queensland Health. Daily data on maximum and minimum temperatures for the same period were supplied by the Australian Bureau of Meteorology. Winter was chosen as the main study season due to it having the highest pediatric influenza incidence. Four Poisson log-linear regression models, with daily pediatric seasonal influenza counts as the outcome, were used to examine the impacts of air pollutants (i.e., ozone (O3), particulate matter≤10μm (PM10) and nitrogen dioxide (NO2)) and temperature (using a moving average of ten days for these variables) on pediatric influenza. The results show that mean temperature (Relative risk (RR): 0.86; 95% Confidence Interval (CI): 0.82-0.89) was negatively associated with pediatric seasonal influenza in Brisbane, and high concentrations of O3 (RR: 1.28; 95% CI: 1.25-1.31) and PM10 (RR: 1.11; 95% CI: 1.10-1.13) were associated with more pediatric influenza cases. There was a significant interaction effect (RR: 0.94; 95% CI: 0.93-0.95) between PM10 and mean temperature on pediatric influenza. Adding the interaction term between mean temperature and PM10 substantially improved the model fit. This study provides evidence that PM10 needs to be taken into account when evaluating the temperature-influenza relationship. O3 was also an important predictor, independent of temperature.