M S Linet

Diagnostic X-ray and ultrasound exposure and risk of childhood cancer

In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer.

Patterns of infection and day care utilization and risk of childhood acute lymphoblastic leukaemia

To investigate if decreased exposure to common childhood infections is associated with risk of childhood acute lymphoblastic leukaemia (ALL) we conducted a case–control study of 1842 newly diagnosed and immunophenotypically defined cases of ALL under age 15, and 1986 matched controls in the US. Data regarding day care, sibship size and common childhood infections were obtained through parental interviews. Data were analysed stratified by leukaemia lineage and separately for ‘common’ childhood ALL (age 2–5 years, CD19, CD10-positive). Neither attendance at day care nor time at day care was associated with risk of ALL overall or ‘common’ ALL. Ear infections during infancy were less common among cases, with odds ratios of 0.86, 0.83, 0.71 and 0.69 for 1, 2–4, 5+ episodes, and continuous infections respectively (trend P = 0.026). No effect of sibship size or birth interval was seen. With one exception (ear infections), these data do not support the hypothesis that a decrease in the occurrence of common childhood infection increases risk of ALL.

CHLORAMPHENICOL USE AND CHILDHOOD LEUKAEMIA IN SHANGHAI

A population-based case-control interview study of 309 childhood leukaemia cases and 618 age and sex matched controls showed a significant dose-response relation between chloramphenicol and risk of both acute lymphocytic leukaemia (ALL) and acute non-lymphocytic leukaemia (ANLL), treatment for more than 10 days being associated with risks of 11.0 and 12.0, respectively. A significant risk of ANLL was also observed with the use of syntomycin, a drug pharmacologically related to chloramphenicol. The risks remained high when analyses were limited to either first or latest use of these antibiotics more than 2 years before diagnosis. Although the association may have non-causal explanations, the results warrant cautious prescribing patterns and further investigations into the leukaemogenic potential of chloramphenicol.

Incidence of haematopoietic malignancies in US radiologic technologists

Background: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. Aims: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. Methods: The investigators followed up 71 894 (77.9% female) US radiologic technologists, first certified during 1926–80, from completion of a baseline questionnaire (1983–89) to return of a second questionnaire (1994–98), diagnosis of a first cancer, death, or 31 August 1998 (731 306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. Results: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin’s lymphoma (118 cases), Hodgkin’s lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). Conclusion: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

Infant vaccinations and risk of childhood acute lymphoblastic leukaemia in the USA

SummaryPrevious studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia. Vaccination histories were compared in 439 children (ages 0–14) diagnosed with acute lymphoblastic leukaemia (ALL) in nine Midwestern and Mid-Atlantic states (USA) between 1 January 1989 and 30 June 1993 and 439 controls selected by random-digit dialing and individually matched to cases on age, race and telephone exchange. Among matched pairs, similar proportions of cases and controls had received at least one dose of oral poliovirus (98%), diphtheria–tetanus–pertussis (97%), and measles–mumps–rubella (90%) vaccines. Only 47% of cases and 53% of controls had received any Haemophilus influenzae type b (Hib) vaccine (relative risk (RR) = 0.73; 95% confidence interval (CI) 0.50–1.06). Although similar proportions of cases (12%) and controls (11%) received the polysaccharide Hib vaccine (RR = 1.13; 95% CI 0.64–1.98), more controls (41%) than cases (35%) received the conjugate Hib vaccine (RR = 0.57; 95% CI 0.36–0.89). Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL, our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia. Further studies are needed to confirm this association and, if confirmed, to elucidate the underlying mechanism.

Central Adiposity, Obesity During Early Adulthood, and Pancreatic Cancer Mortality in a Pooled Analysis of Cohort Studies

BACKGROUND Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project

Background:Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women.Methods:In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248).Results:Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22–5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82–1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility.Conclusions:The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Childhood cancer in the offspring born in 1921–1984 to US radiologic technologists

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921–1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2–1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (⩾82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7–4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983–2008

Background:Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality.Methods:One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983–2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983–2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors.Results:Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03–0.39) with similar patterns for mortality among technologists born before 1930.Conclusions:Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

A population-based case-control study of childhood leukemia in Shanghai

A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patients prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio [OR] = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.