The C3435T polymorphism of MDR1 and susceptibility to adult glioma

INTRODUCTION: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents potentially carcinogenic substances from crossing the blood-brain barrier. We compare adult glioma cases and controls for the C3435T polymorphism that has been associated with reduced MDR1 expression. METHODS: Adult glioma in the San Francisco Bay area and population-based controls were identified between 1991-1994 and 1997-1999. Genotyped cases (n = 458) and controls (n = 528) were compared using logistic regression controlling for age, gender and ethnicity, with later stratification by ethnicity, gender and histology. RESULTS: With CC as the referent, the TT genotype was nonsignificantly less frequent among cases compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0). CONCLUSIONS: Although the C3435T polymorphism does not appear to be associated with other types of glioma, we cannot rule out that this MDR1 polymorphism may be associated with glioblastoma among men.     

Regional block and DVT prophylaxis

The last few years have seen increasing concerns among anaesthetistsabout the risks of pharmacological prophylaxis for thromboembolicdisease. Increased bleeding during or after surgery is one concern,but of greater significance is the possibility of an increasedpredisposition to haematoma formation when regional block isused. Most of the recent consideration of this problem has beenin relation to vertebral canal haematoma formation after centralnerve block. Some thought must be given also to the possibilityof haematoma formation after peripheral techniques when thetarget nerve is deeply placed so that pressure cannot be usedto control bleeding after needle insertion. However, this reviewwill be focused on vertebral canal haematoma.     

Reduced immunoglobulin E and allergy among adults with glioma compared with controls

We and others have reported previously that adults with glioma are 1.5- to 4-fold less likely than controls to report a variety of allergic conditions. The consistent nature of this relationship calls for a biological explanation so that preventative or therapeutic modalities can be explored. We enrolled 403 newly diagnosed adult glioma cases in the San Francisco Bay Area over a 3-year period using a population-based cancer registry and 402 age/gender/ethnicity frequency-matched controls identified via random digit dialing. We assessed total, food-specific, and respiratory-specific IgE in available case (n = 228) and control (n = 289) serum samples. IgE levels were associated with gender, age, smoking status, and ethnicity among cases and/or controls. Among the cases, IgE levels were not associated with aspects of glioma therapy including radiation, chemotherapy, or tumor resection. Total IgE levels were lower in cases than controls: age/gender/ethnicity/education/smoking-adjusted odds ratio (OR) for elevated versus normal total IgE was 0.37 [95% confidence interval (CI), 0.22-0.64]. For the food panel, OR was 0.12 (95% CI, 0.04-0.41). For the respiratory panel, OR was 0.76 (95% CI, 0.52-1.1). Among respiratory allergies, late age of onset (>12 years) but not IgE levels defined a group with strong associations with risk (OR, 0.50; 95% CI, 0.33-0.75). These results corroborate and strengthen our findings of an inverse association between allergic reactions and glioma by showing a relationship with a biomarker for allergy and cancer for the first time. Furthermore, the results indicate a complex relationship between allergic disease and glioma risk that varies by allergen and allergic pathology.     

Aberrant methylation of p16INK4a in anatomic and gender-specific subtypes of sporadic colorectal cancer.

Colorectal cancer (CRC) occurring in the proximal colon and among women may represent a distinct subtype of the disease. In the present study of 120 sporadic CRCs, we used methylation-specific PCR to test whether methylation of the CpG island in the 5' region of the p16INK4a tumor suppressor gene was associated with anatomical location, gender, or other clinicopathological characteristics. Overall, 18.3% of the tumors had detectable p16INK4a methylation. A marked preponderance of methylated tumors occurred within the proximal colon; cancers occurring proximal to the sigmoid colon were 13.1 times more likely to contain methylated p16INK4a compared with distal tumors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16INK4a methylation was also associated with poorly differentiated tumors. The localization of tumors with p16INK4a methylation within the proximal colon and among female patients specifically adds to a growing database of molecular alterations that define important subtypes of sporadic CRC. The potentially reversible nature of CpG methylation may provide novel therapeutic opportunities for this increasing subtype of the disease, which, due to anatomical location, presents a great challenge for early detection.     

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.