K J Bunch

A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006

We conducted a large record-based case–control study testing associations between childhood cancer and natural background radiation. Cases (27 447) born and diagnosed in Great Britain during 1980–2006 and matched cancer-free controls (36 793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother’s residence at the child’s birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI −4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ∼50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

Cancer incidence in children conceived with assisted reproduction technology

lacrimal gland; and -defensin-2 message in cornea and conjunctiva but not lacrimal gland. -defensins 5 and 6 were absent. Purified or recombinant defensins may be useful treatments for eye infections because defensins have a broad spectrum of activity, are chemotactic for monocytes, accelerate wound healing, and may be non-antigenic, whereas most antibiotics have a comparatively limited spectrum of activity, interfere with healing due to ocular surface toxicity, and may produce allergic reactions. Defensins may be effective in the treatment of established ocular-surface infections or prevention of keratitis in eyes at particular risk, such as dry-eye states, contact-lens wearers, critically ill or comatose patients, or after ophthalmic surgery. Factors that control the production of defensins are unknown and it is likely that some of the risk factors mentioned above are associated with down-regulation of production.

Cancer risk among children born after assisted conception.

BACKGROUND Accurate population-based data are needed on the incidence of cancer in children born after assisted conception. METHODS We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility. RESULTS The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight. CONCLUSIONS There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).

Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004.

Background:Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs).Methods:This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated.Results:We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3–16.5) in heritable cases and 1.5 (0.9–2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2–1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4–651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6–32.4)).Conclusion:The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases

BACKGROUND High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. METHODS We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. RESULTS Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. CONCLUSIONS Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

Genetic influences on clinical mastitis and its relationship with milk yield, season and stage of lactation

Abstract Milk yield and clinical mastitis records were collected from 1672 cows in 24 dairy herds in southern England. The incidence of mastitis in each of the first two lactations was statistically analysed for herd, 305-day milk yield, length of lactation, age at first calving, season of calving and stage of lactation. A subset of the data, relating to 890 cows, the daughters of 34 sires, was used to obtain estimates of heritability of the incidence of mastitis. Genetic correlations between milk yield and mastitis were also calculated. The average incidence of mastitis was found to be 16% in the first lactation and 20% in the second. Variation in the incidence of mastitis could, for a large part, be attributed to variation amongst herds. The incidence of mastitis in sire groups varied significantly in the first lactation, but not in the second. Averaging over both lactations, the heritability estimate for incidence of mastitis was 0.12±0.09. There were significant positive correlations among herds between the incidence of mastitis and 305-day milk yield, but genetic correlations were, on the whole, small. The level of mastitis incidence did not change with increasing milk yield in cows which lactated for at least 305 days, but it did increase slightly with increasing milk yield in cows which lactated for shorter periods. Season of calving had little effect on the overall incidence of mastitis during a lactation, although cows which calved in winter tended to have mastitis earlier in lactation than those which calved during the other half of the year. About two fifths of cases occurred on average before 30 days post-calving. The incidence of mastitis in the second lactation seemed to vary according to age at first calving particularly in those cows calving for the first time in summer.

Cardiac or cardiopulmonary transplantation in childhood cancer survivors: an increasing need?

Childhood cancer patients now have an excellent survival rate. Anthracyclines and radiation have contributed to this success, unfortunately at a cost. Both modalities are cardiotoxic and in some cases this is fatal unless treated by cardiac transplantation. This population-based study investigates the requirement for transplantation, patient demographics and transplant outcomes. Childhood cancer survivors requiring a subsequent cardiac or cardiopulmonary transplant were identified by record linkage between the National Registry Childhood Tumours (NRCT) and United Kingdom Transplant registry (UKT). The clinical details were obtained from the treatment centres for confirmed matches. Forty-three patients were identified as requiring cardiac transplantation: 36 underwent transplantation, 4 died while waiting and 3 were removed from the list. Their childhood cancers included 21 haematopoietic and 22 solid tumours diagnosed at a median age of 3.00 years (range 0.11-13.92 years). All patients were treated with anthracyclines (210-750 mg/m(2)) and 15 received cardiac radiation. The median age at cardiac transplantation was 14.80 years (range 3.26-23.92 years) and actuarial survival for the 36 who underwent cardiac transplantation was 74% and 67% at 5 and 10 years, respectively. A further three patients underwent heart/lung transplantation: all three died from transplant-related causes. Cardiac transplantation is a realistic option for cancer survivors, with survival rates comparable with those of other cardiac recipients. This study demonstrates that, over three decades, there has been an increased requirement for cardiac transplantation among childhood cancer survivors. Future planning for long term survivors needs to take this into account.

Variations in some inorganic components and physical properties of claw keratin associated with claw disease in the British Friesian cow

Abstract Horn hardness, water content and mineral composition were measured in the feet of 42 Friesian cows, 27 with no history and 15 with a history of lameness. Water content and magnesium concentration increased with age, potassium concentration was lower in the hooves of pregnant animals, but none of the variates was affected by lactation. Horn hardness was related to composition, the harder keratin of the claw wall containing more calcium, copper, zinc and phosphorus and lower concentrations of water, sodium, potassium and iron than the heel. Zinc concentration was lower in the horn of lame animals but those of magnesium and copper were increased. Mineral composition varied significantly with respect to the position of the horn in the claw (heel, sole or wall). The results are discussed with regard to the function of the horn constituents.

Residential distance at birth from overhead high-voltage powerlines : childhood cancer risk in Britain 1962-2008

Background:We extend our previous study of childhood leukaemia and proximity to high-voltage powerlines by including more recent data and cases and controls from Scotland, by considering 132-kV powerlines as well as 275 and 400 kV and by looking at greater distances from the powerlines.Methods:Case–control study using 53 515 children from the National Registry of Childhood Tumours 1962–2008, matched controls, and calculated distances of mother’s address at child’s birth to powerlines at 132, 275, and 400 kV in England, Wales and Scotland.Results:Our previous finding of an excess risk for leukaemia at distances out to 600 m declines over time. Relative risk and 95% confidence interval for leukaemia, 0–199 m compared with>1000 m, all voltages: 1960s 4.50 (0.97–20.83), 2000s 0.71 (0.49–1.03), aggregate over whole period 1.12 (0.90–1.38). Increased risk, albeit less strong, may also be present for 132-kV lines. Increased risk does not extend beyond 600 m for lines of any voltage.Conclusions:A risk declining over time is unlikely to arise from any physical effect of the powerlines and is more likely to be the result of changing population characteristics among those living near powerlines.

Cancer in the offspring of female radiation workers: a record linkage study

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the childs conception may be at an increased risk of childhood cancer. An additional 16 964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52 612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.