Islet autoantibody profiles associated with higher diabetes risk in Lithuanian compared with English schoolchildren.

During a 15-year period, the incidence of type 1 diabetes has doubled in Lithuania, while increasing by a third in England; however, England still has a higher incidence. Analysis of sera collected from non-diabetic schoolchildren from Lithuania and England more than 20 years ago showed a similar number of multiple autoantibody-positive schoolchildren between the populations, but a higher prevalence of islet antigen-2 autoantibodies (IA-2A) in English schoolchildren. We aimed to use recently developed, more specific islet autoantibody tests to characterize differences in humoral autoimmunity between these two general population cohorts in greater detail. Samples from 88 Lithuanian and 133 English schoolchildren previously found islet autoantibody-positive were selected for measurement of additional islet autoantibodies by radioimmunoassay. Samples were tested for autoantibodies to zinc transporter 8 (ZnT8A), GAD (96-585), the protein tyrosine phosphatase region of islet antigen-2 (PTPA) and the related IA-2ßA, while autoantibodies to IA-2A were reassayed using the current harmonized method. IA-2-related autoantibodies PTPA (0·13 versus 0·45%, P = 0·027) and IA-2ßA (0 versus 0·35%, P < 0·001), but not IA-2A measured using the harmonized method, were less common in Lithuanian compared to English schoolchildren. Lithuanian schoolchildren who were islet autoantibody-positive were positive for fewer biochemical autoantibodies compared with English schoolchildren (P = 0·043). Background rates of islet autoimmunity in childhood differ subtly between countries, which have different incidences of type 1 diabetes. The optimal screening strategy (age and combination of markers) for detection of islet autoimmunity may vary between countries, dependent upon the pattern of autoantibodies found in the general population.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study.

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.

Mortality in Barrett's esophagus: three decades of experience at a single center.

BACKGROUND AND STUDY AIMS: There is a view that the majority of deaths in patients with Barrett's esophagus are from causes other than esophageal adenocarcinoma (EAC). The aim of this analysis was to establish the pattern of mortality for a number of causes in patients with Barrett's esophagus. PATIENTS AND METHODS: This was a single-center prospective cohort study of patients from Rotherham District General Hospital, which is a secondary referral center. The cohort consisted of 1239 patients who were diagnosed with Barrett's esophagus between April 1978 and March 2009.  Follow-up for mortality was undertaken by "flagging" the patients with the NHS Information Center. Causes of death were compared with UK Office of National Statistics age- and sex-specific mortality data for 1999, the median year of diagnosis. Analysis was by a "person - years at risk" calculation from date of diagnosis. RESULTS: The ratio of observed deaths from EAC compared with those expected in this cohort was 25.02 - a very large excess. There was no difference in mortality from colorectal cancer or circulatory disease and there were fewer deaths from cancers other than esophageal adenocarcinoma and colon cancer compared with national statistics. There was a small statistically significant difference in mortality from all causes but this disappeared completely when deaths from esophageal adenocarcinoma were excluded. CONCLUSIONS: Overall, mortality in Barrett's esophagus is increased significantly but only as a result of the large excess of deaths from EAC. This strengthens the case for endoscopic surveillance if successful interventions can be undertaken in patients with Barrett's esophagus to prevent development of esophageal adenocarcinoma.

A survey of dietary nitrate in well-water users.

The hypothesis that high nitrate ingestion may increase the risk of stomach cancer has led to concern over rising levels of nitrate in drinking water, but with little consideration as to whether nitrate from water makes a major contribution to total nitrate intake. In order to investigate the relative importance of water and food as sources of nitrate, 404 adult well-water users completed a diet diary over a 48-hour period and provided a 24-hour urine specimen and a sample of their drinking water. Where the waterborne nitrate level is less than 50 mg/I, as recommended by the World Health Organization (WHO), 30% of ingested nitrate is from water. As the well-water nitrate concentration rises the contribution of water to daily intake increases; at levels between 50 and 100 mg/I, on average, nearly 70% of daily intake is from water, and above 100 mg/I over 80% of daily intake is waterborne. Thus it is only at levels above those currently recommended by the WHO that waterborne nitrate appears to be the major contributor to total nitrate intake.

Fish, n-3 fatty acids and human colorectal and breast cancer mortality.

Although there is a strong positive association between total fat consumption and colorectal and breast cancer risk, there is evidence that n-3 fatty acids, mainly found in fish oil, are protective. If this is so, we would expect to be able to detect an inverse correlation between fish consumption and colorectal cancer and breast cancer mortality. Mortality data for breast and colorectal cancer in 24 European countries were correlated with current fish and fish oil consumption and with consumption 10 and 23 years previously. In males there was an inverse correlation between colorectal cancer mortality and current intake of fish (P = 0.036), a weaker correlation with fish consumption 10 years earlier (P = 0.042) and none with consumption 23 years earlier (P = 0.12). The data were not statistically significant in females. There was no correlation at all between breast cancer mortality and fish or fish oil consumption at any time. It is concluded that fish consumption is associated with protection against the later promotional stages of colorectal carcinogenesis, but not with the early initiation stages. The results are discussed in terms of the role of prostaglandins in colorectal carcinogenesis.

Relationship between the intake of high-fibre foods and energy and the risk of cancer of the large bowel and breast.

A recent analysis of Food and Agriculture Organization (FAO) data and mortality data has shown that not all fibre sources are equally protective against colorectal and breast cancers. We correlated the risk of cancers of the colon and breast with the intake of cereals, starchy roots, vegetables, fruits and total energy, either concurrently with the cancer mortality data, or from 20 years earlier. The patterns of the effects of cereals, starchy roots, vegetables and fruits were very different, with cereals and vegetables being protective against both cancers, fruit having no effect and starchy roots having a very weak and non-significant promoting effect. There is strong current interest in the protective effects of fruit and vegetables against cancers at a number of sites. Our analysis showed that only the current intake of vegetables was protective. Intake early in life seemed to offer no protection. The protective effect of cereals was manifest both early in life as well as for current intake for female breast and colorectal cancer, but only for the current period for male colorectal cancer. Calorie restriction, but only early in life, provides protection against all three cancers. Most advice on healthy eating, other than that for small children, is given to (and taken by) the senior age groups and these are the ones likely to benefit. In our study fruit intake was not correlated at all with the risk of either colorectal or breast cancers at either time period. Fruit is clearly more protective against cancers of the upper digestive tract and respiratory tract than against the cancers considered here.

Increased risk of cancer mortality after vagotomy for peptic ulcer: a preliminary analysis.

Patients (1,643) undergoing vagotomy for peptic ulcer at York District Hospital were traced through the Office of Populations Censuses and Surveys (OPCS) and cause of mortality obtained for the 577 who had died. Expected mortality for the cohort was calculated using a years at risk calculation in 5 year bands. There was an excess risk of mortality from cancer of all sites (1.5-fold), stomach (1.6-fold), colorectum (1.7-fold), biliary tract (4.1-fold) and lung (1.6-fold). There was no excess risk or mortality from cancer of the oesophagus, pancreas and female breast. The numbers of deaths have been too few and length of follow-up too short to investigate latency. The findings are consistent with the production of carcinogens as a result of the hypoacidity following vagotomy.

An initial comparison of nine centres registering patients with the UK National Barrett's Oesophagus Registry (UKBOR).

Initial data from the first nine hospitals registering at least 50 patients each with UKBOR were analysed. This involved 2102 Barrett's oesophagus (BO) cases (M1261:F841), mean 234 patients per centre (range 73-636) and M:F ratio 1.5 (range 1.1-2.3). There was an equal geographical distribution of the hospitals, three each in the north of the country (N), Midlands (Mid) and the south of the country (S). The catchment populations varied from 145,000 to 450,000. The M:F ratio for N, Mid and S was 1.6, 1.3, 1.7, respectively. The mean age at diagnosis in males was 62.0 years (range 53.2-66.3) and in females 67.6 years (range 59.3-73.4), with little geographical variation. The age distribution varied somewhat between the centres; the peak age for males being 40-49 years in one northern hospital, 60-69 years in seven others and 70-79 years in one hospital. For females it was 60-69 years and 70-79 years in each of four hospitals, and 80-89 years in one. The BO diagnosis rate in the under 50s was fairly constant; F mean 14% (range 0-23%); M (eight centres) mean 23% (range 16-27%). However, in one northern centre it was much higher (43%). Information on patients with a diagnosis of oesophageal adenocarcinoma (AC) was available from seven centres. A total of 59 AC were diagnosed (M44:F15, ratio 2.9). The overall mean rate of AC in BO was 3.6% (range 0.5-7.5%). Minor variations in BO patient characteristics may have been due to the hospitals' different policies on diagnostic and reporting criteria. However, the much higher percentage of men under age 50 in the one N centre may reflect a genuine difference in diet and lifestyle, or possibly genetic susceptibility.

The association between typhoid carriage, typhoid infection and subsequent cancer at a number of sites.

It has been demonstrated that bacteria can produce the very potent carcinogens (N-nitroso compounds), from nitrite and suitable amines. It has been hypothesized that this can happen whenever a body site which is normally sterile becomes colonized by bacteria. If this is so then such chronic infections should result in an increased incidence of local cancers and also of cancers at some distant sites. To test this we studied the risk of cancer at various sites in a cohort of chronic carriers of Salmonella typhi/paratyphi. We have observed a greatly increased risk of cancers of the biliary tract and also of cancers of the colorectum, pancreas, lung and all sites. The results are discussed in terms of the hypothesis being tested.

A single centre's 20 years' experience of columnar-lined (Barrett's) oesophagus diagnosis.

BACKGROUND: The pattern of oesophageal carcinoma type has been changing for some time in a number of countries, with adenocarcinoma becoming more frequent OBJECTIVE: To investigate the prevalence of columnar-lined (Barrett's) oesophagus and oesophageal adenocarcinoma in Barrett's oesophagus during a 20-year period in a single centre. METHODS: All upper gastrointestinal endoscopy and histology reports for the period January 1977 to December 1996 inclusive were reviewed. Data were analysed from patients who had histologically proven Barrett's oesophagus. The data were analysed as a single cohort and in five-year bands according to the date of diagnosis. RESULTS: Of 44,721 endoscopies, 636 Barrett's oesophagus cases were diagnosed; 508 (323 males 185 females; M:F ratio 1.7) were histologically proven. The frequency of Barrett's oesophagus detection increased steadily from 0.2% to 1.6% of all endoscopies per five-year band. The M:F ratio and the mean ages at diagnosis (61 years, range 60-63 for males and 69 years, range 68-79 for females) remained constant throughout. Barrett's oesophagus was diagnosed at a younger age in males (peak 60-69 years) compared to females (peak 70-79 years). The male oesophageal adenocarcinoma incidence (11.1%) was almost twice that in females (6.5%). In the majority (81%), the initial diagnosis of oesophageal adenocarcinoma and Barrett's oesophagus was made concurrently. CONCLUSIONS: The increasing Barrett's oesophagus frequency may reflect an increasing incidence or recognition of this condition or both. Barrett's oesophagus males are more likely to develop oesophageal adenocarcinoma than females.

Trends in European breast cancer incidence and possible etiology.

In this study the trends in breast cancer incidence in a number of European countries, over the last 20 years, have been evaluated. There is a wide range in incidence; the risk being highest in north and west Europe (and highest in Switzerland) and lower in south and in east Europe. There was little difference, however, between countries in the incidence of the disease occurring before the menopause, and this incidence has shown little temporal change in the time period 1960-1985. Indeed, in many countries there has been little change in incidence in any age band since 1975. The use of oral contraception has been claimed to be a risk factor in premenopausal breast cancer. In two countries, the data on oral contraceptive usage were available; in neither was there any evidence that the introduction and growth in such usage was related to the risk of breast cancer in any age band that might have been exposed to them. The reasons for this are discussed in the light of recent reports to the contrary.