Causes of death in patients with rheumatoid arthritis: comparison with siblings and matched osteoarthritis controls.

OBJECTIVE: Survival of patients with rheumatoid arthritis (RA) is reduced when compared to the general population. We assessed differences in causes and age of death between patients with RA and their siblings. Comparisons were also made with a control group of subjects with lower limb osteoarthritis (OA). METHODS: A population of 257 patients with RA studied in 1991 was compared to 371 of their same-sex siblings and 485 patients with hip and knee OA who were also attending the department at this time. Death certificates were obtained and compared. RESULTS: Among patients with RA, 54% (139/257) were deceased, compared to 28% (105/371) of the siblings and 32% (154/485) of OA patients (RA vs siblings or OA, p < 0.05). There were more deaths due to ischemic heart disease (IHD) in both the RA and OA groups compared to those expected; ratio observed/expected, 1.66 (95% CI 1.01, 2.79) and 1.96 (95% CI 1.21, 3.25), respectively, but not for siblings: observed/expected = 1.05 (95% CI 0.53, 2.08). There was a significant deficit in cancer related deaths in RA patients, observed/expected = 0.62 (95% CI 0.36, 1.03). CONCLUSION: Significantly more patients with RA had died than in either of the comparator populations. RA and OA patients died more frequently of IHD than the siblings. The RA population had a 40% reduced rate of cancer related deaths than expected and compared to their siblings.

Examination of gender effect in birth weight and miscarriage associations with childhood cancer (United Kingdom).

BACKGROUND: Higher birth weight and maternal history of miscarriage has been associated with an increased risk of childhood leukemia. The possibility that this association may be sex-specific has not been explored in detail in previous studies. METHODS: In a retrospective case-control study, 732 childhood (< or =14 years) cancer cases from a population-based Registry in Northern England whose hospital birth records could be accessed and 3,723 controls matched for date and hospital of birth to the cases were compared. We examined birth weight for sex-specific associations with childhood cancer. Conditional logistic regression analysis was used for statistical evaluation of associations. RESULTS: In acute lymphoblastic leukemia (ALL) (225 cases and 1,163 matched controls), birth weight and sex showed a strong interaction (P = 0.003). In boys with ALL, but not in girls, there was a nonlinear association with birth weight (P for trend = 0.008; OR = 3.05 for the highest quintile compared to the second lowest quintile, 95% CI = 1.40-6.64; P = 0.005). When birth weights were adjusted using UK standards for gestational age and sex, the risk associations were similar in statistical significance and magnitude. Maternal history of miscarriage showed an association with all cancers and individually with ALL. The miscarriage association with ALL was statistically significant in boys only (OR = 1.91, 95% CI = 1.07-3.42; P = 0.03). A multivariable model for ALL containing other examined maternal and reproductive variables confirmed the independence of the birth weight and miscarriage associations. There was no birth weight or miscarriage associations in other cancers. CONCLUSIONS: This study confirmed the risk associations with birth weight and miscarriages in childhood ALL. Statistically significant association of size at birth suggested marked differences in etiology between girls and boys.

Paternal occupational exposure to electro-magnetic fields as a risk factor for cancer in children and young adults: a case-control study from the North of England.

BACKGROUND: Numerous studies have implied that paternal occupational exposures, in particular electromagnetic fields (EMF) and ionizing radiation, may be involved in the etiology of childhood cancers. We investigated whether an association exists between paternal occupations at birth involving such exposures and cancer risk in offspring, using data from the Northern Region Young Persons' Malignant Disease Registry (NRYPMDR). PROCEDURE: Cases (n=4,723) were matched, on sex and year of birth, to controls from two independent sources: (i) all other patients from the NRYPMDR with a different cancer, (ii) 100 cancer-free individuals per case from the Cumbrian Births Database. An occupational exposure matrix was used to assign individuals to exposure groups. RESULTS: There was an increased risk of leukemia among the offspring of men employed in occupations likely to be associated with EMF or radiation exposures (OR 1.31, 95% CI 1.02-1.69), particularly in males aged less than 6 years (OR 1.81, 95% 1.19-2.75). No significant association was seen in females. Increased risks were also seen for chondrosarcoma (OR 8.7, 95% CI 1.55-49.4) and renal carcinoma (OR 6.75, 95% CI 1.73-26.0). These associations were consistent between control groups and remained after adjustment for socio-economic status. CONCLUSIONS: This large case-control study identified a significantly increased risk of leukemia among the offspring of men likely to have been occupationally exposed to EMF, with differing associations between males and females. Increased risks of chondrosarcoma and renal carcinoma were also seen, although based on smaller numbers. Further detailed investigations in this area are required to understand this association.

Paternal occupational exposure to pesticides or herbicides as risk factors for cancer in children and young adults: a case-control study from the North of England.

Researchers in numerous studies have suggested that preconception paternal occupational exposures to various substances, including pesticides and herbicides, may be involved in the etiology of childhood cancers. Using data from the Northern Region Young Persons' Malignant Disease Registry, the authors investigated whether paternal occupations likely to involve such exposures, as recorded at the time of a child's birth, were associated with children's cancer risk. The authors matched cases (n = 4,723), on sex and year of birth, to controls from 2 independent sources: (1) all other patients from the registry with a different cancer and (2) 100 cancer-free individuals per case from the Cumbrian Births Database. An inverse association existed, particularly in males, between lymphoid leukemia and paternal occupations with likely exposures to pesticides and/or herbicides. However, this was not significant after stratifying by residential status (urban versus rural). Results do not support a role for preconception paternal occupational exposures to pesticides or herbicides in the etiology of childhood cancer.

Folic acid supplementation and social deprivation.

OBJECTIVE: To assess the use of folic acid supplementation in relation to small-area measures of social deprivation. DESIGN: Cohort study. SETTING: Antenatal clinic, Women's Outpatients Services, Cumberland Infirmary, Carlisle, UK. SUBJECTS: Four hundred and fifty women attending their 18-week antenatal clinic appointment. No selection criteria were applied. Townsend scores were allocated using postcodes to provide a small-area measure (enumeration district) of social deprivation. RESULTS: Eighty-nine per cent of women took folic acid prior to their 18-week antenatal clinic appointment; 48% of women took folic acid before 4 weeks of gestation. Younger women and more socially deprived women were less likely to use folic acid supplements before 4 weeks of gestation. Women with a family history of neural tube defects were no more likely to take folic acid than were women with no family history of neural tube defects. CONCLUSION: A high proportion of women reported taking folic acid supplements during pregnancy but less than half took them at the most important time in early pregnancy. Younger women and women who were more socio-economically deprived were much less likely to take folic acid during the critical periconceptional period. Future strategies should promote prenatal folic acid supplementation in women under the age of 24 and in women of low socio-economic status. Further attention should also be given to the use of folic acid supplements in women with a family history of neural tube defects.

Second primary tumors in children and young adults in the North of England (1968-99).

BACKGROUND: This study describes the risk of second malignancy in patients diagnosed with cancer under the age of 25 years, registered on the Northern Region Young Person's Malignant Disease Registry. PROCEDURE: Incidence rates were calculated to describe the occurrence of second malignancies, rate ratios were estimated to compare rates between subgroups. Standardized incidence ratios (SIRs) were calculated for comparison with a reference population. RESULTS: There were 4,072 children and young adults diagnosed with a first malignancy from 1968 to 1999, of whom 68 had a second malignancy (including basal cell carcinomas and meningiomas). The incidence rate of second malignancy is 1.7 per 1,000 survivor person-years (95% CI: 1.4, 2.2), reflecting a four-fold increased risk of malignancy compared with the general population. The rate of second malignancy was non-significantly higher for those diagnosed during young adulthood rather than childhood (RR = 1.2, 95% CI: 0.7, 2.0), significantly higher in females than males (RR = 1.8, 95% CI: 1.1, 3.0) and significantly lower for those diagnosed in more recent years (RR = 0.4, 95% CI: 0.2, 0.8). In contrast, the SIRs indicated that children were at substantial increased risk; whilst males and females, and those diagnosed in earlier and later time periods, were at equivalent risks. CONCLUSIONS: There is evidence of a sustained increased risk of second malignancy in those treated for primary cancer, especially those diagnosed in childhood; with no evidence that this risk is reducing.

DNA repair gene polymorphisms, pre-natal factors and the frequency of somatic mutations in the glycophorin-A gene among healthy newborns.

This study investigates variation in somatic mutation frequency, as measured by the glycophorin-A (GPA) somatic mutation assay, in relation to polymorphic variation among 435 newborn babies in DNA repair genes XRCC1, XRCC3 and XRCC4 and gender, parental age, social class and smoking habits. The three polymorphisms under investigation were an Arg --> Gln substitution at codon 399 in exon 10 of XRCC1, a Thr --> Met substitution at codon 241 in exon 7 of XRCC3 and an Ile --> Thr substitution at codon 401 in exon 4 of XRCC4. The study population is an extension of that previously analysed for GPA mutations and XRCC1 polymorphisms. A significant difference was seen in the earlier work in the genotype distribution for the XRCC1 Arg399Gln polymorphism between the main population and the small number with extreme values for NN variant frequency and this was maintained in the larger study group (OR 3.20 [95% CI: 1.16, 8.81]) P = 0.043). No such association was seen for XRCC3 or XRCC4 polymorphisms. When adjustments were made for multiple testing, neither N0 nor NN variant frequencies in the main study population were found to be influenced by the polymorphisms in XRCC1, XRCC3, or XRCC4. In addition, neither maternal or paternal smoking, age or social class nor the gender of the offspring were found to affect variant frequencies nor were variant frequencies influenced by any interaction between any of these factors and genotype. It is concluded that the genotypic variation in DNA repair genes examined in this study has no discernable effect on the genesis of the somatic mutations observed at birth.