Julian Little

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.

BACKGROUND & AIMSnEpidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations.nnnMETHODSnWe randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy.nnnRESULTSnAmong the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001).nnnCONCLUSIONSnDaily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.

Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study

BACKGROUNDnCongenital heart defects are generally assumed to have a multifactorial aetiology. We have tested this hypothesis by studying adults with heart defects and their families.nnnMETHODSnWe identified 1094 patients who survived surgery for major cardiac defects before 1970. We chose individuals with disturbance of situs or segmental connection, with atrioventricular septal defect or with tetralogy of Fallot. After exclusion and non-participation, 727 individuals were traced. Each was visited by an investigator and completed a detailed questionnaire. If possible, all normal offspring were examined by a paediatric cardiologist.nnnFINDINGSnThe 727 individuals had 393 live offspring. There were 71 miscarriages and five terminated pregnancies. Overall, we found recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This result differed significantly from sibling risk (2.1%; p=0.021). More congenital heart defects occurred in the offspring of affected women than in those of affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the offspring were taken into account the excess was more significant (p=0.032). We found an excess of miscarriages in the offspring of affected women (p=0.001). In tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12 (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight (0.3%) of 2728 third-degree relatives.nnnINTERPRETATIONnOur findings do not support a polygenic basis for all heart defects. Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes. Our data suggest that isolated transposition of the great arteries is a sporadic defect.

Tobacco smoking and oral clefts: a meta-analysis

OBJECTIVEnTo examine the association between maternal smoking and non-syndromic orofacial clefts in infants.nnnMETHODSnA meta-analysis of the association between maternal smoking during pregnancy was carried out using data from 24 case-control and cohort studies.nnnFINDINGSnConsistent, moderate and statistically significant associations were found between maternal smoking and cleft lip, with or without cleft palate (relative risk 1.34, 95% confidence interval 1.25-1.44) and between maternal smoking and cleft palate (relative risk 1.22, 95% confidence interval 1.10-1.35). There was evidence of a modest dose-response effect for cleft lip with or without cleft palate.nnnCONCLUSIONnThe evidence of an association between maternal tobacco smoking and orofacial clefts is strong enough to justify its use in anti-smoking campaigns.

Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.

Role of medical history in brain tumour development. Results from the international adult brain tumour study

In an international population‐based case‐control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age‐ and gender‐matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti‐epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation. Int. J. Cancer82:155–160, 1999.

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

Objective: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Design: Retrospective population based study. Setting: Population of the Grampian region of Scotland. Participants: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. Results: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). Conclusion: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

Rural and urban differences in stage at diagnosis of colorectal and lung cancers

There is evidence that patients living in outlying areas have poorer survival from cancer. This study set out to investigate whether they have more advanced disease at diagnosis. Case notes of 1323 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. Of patients with lung cancer, 42% (69/164) living 58 km or more from a cancer centre had disseminated disease at diagnosis compared to 33% (71/215) living within 5 km. For colorectal cancer the respective figures were 24% (38/161) and 16% (31/193). For both cancers combined, the adjusted odds ratio for disseminated disease at diagnosis in furthest group compared to the closest group was 1.59 (P = 0.037). Of 198 patients with non-small-cell lung cancer in the closest group, 56 (28%) had limited disease (stage I or II) at diagnosis compared to 23 of 165 (14%) of the furthest group (P = 0.002). The respective figures for Dukes A and B colorectal cancer were 101 of 196 (52%) and 67 of 172 (39%) (P = 0.025). These findings suggest that patients who live remote from cities and the associated cancer centres have poorer chances of survival from lung or colorectal cancer because of more advanced disease at diagnosis. This needs to be taken into account when planning investigation and treatment services.

Impact of deprivation and rural residence on treatment of colorectal and lung cancer.

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment.

Socioeconomic status and orofacial clefts in Scotland, 1989 to 1998.

OBJECTIVEnThe purpose of this study was to investigate the association between socioeconomic status and orofacial clefts (OFC) in Scotland.nnnDESIGNnStudy of prevalence at birth over a 10-year period using an area-based measure of material deprivation.nnnSETTINGnPopulation-based study throughout Scotland.nnnPARTICIPANTSnEight hundred thirty-four live births with OFC born between January 1, 1989, and December 31, 1998, ascertained from the nationwide register of the Cleft Service in Scotland, compared with the total 603,825 live births in Scotland in this period.nnnRESULTSnThere was a strong positive relationship whereby the prevalence of OFC at birth increased with increasing deprivation. This trend was statistically significant for cleft lip and/or palate (CL[P]: p =.016) but not for cleft palate (CP; p =.078). For each type of cleft, the relative risk among those resident in the most deprived areas, compared with those resident in the least deprived areas, was 2.33.nnnCONCLUSIONSnThe association between OFC and socioeconomic status is consistent with a report for an earlier period in a smaller part of Scotland. Unlike the earlier study, this pattern appears to be stronger for CL(P) than for CP. These observations do not appear to be an artifact of recording. It is possible that they reflect the association between deprivation and risk factors for OFC, most likely tobacco smoking during pregnancy. Because the relationship between OFC and socioeconomic status appears to have been virtually unstudied in other populations, it would be valuable to investigate this relationship elsewhere and determine whether known risk factors account for the relationship.

Dietary flavonoid intake and colorectal cancer: a case-control study.

Diets rich in flavonoids may reduce the risk of developing colorectal cancer. Flavonoids are widely distributed in foods of plant origin, though in the UK tea is the main dietary source. Our objective was to evaluate any independent associations of total dietary and non-tea intake of four flavonoid subclasses and the risk of developing colorectal cancer in a tea-drinking population with a high colorectal cancer incidence. A population-based case-control study (264 cases with histologically confirmed incident colorectal cancer and 408 controls) was carried out. Dietary data gathered by FFQ were used to calculate flavonoid intake. Adjusted OR and 95 % CI were estimated by logistic regression. No linear association between risk of developing colorectal cancer and total dietary flavonol, procyanidin, flavon-3-ol or flavanone intakes was found, but non-tea flavonol intake was inversely associated with colorectal cancer risk (OR 0.6; 95 % CI 0.4, 1.0). Stratification by site of cancer and assessment of individual flavonols showed a reduced risk of developing colon but not rectal cancer with increasing non-tea quercetin intake (OR 0.5; 95 % CI 0.3, 0.8; P(trend) < 0.01). We concluded that flavonols, specifically quercetin, obtained from non-tea components of the diet may be linked with reduced risk of developing colon cancer.