There has been recent interest in the possibility that breast cancer can have a prenatal origin (Trichopoulos, 1990). Various studies have reported on the relationship between birthweight, taken as a marker of prenatal environment, and breast cancer, but with differing results. One study (Ekbom et al, 1992; reported no association between birthweight and breast cancer, two (Le Marchand et al, 1988;Sanderson et al, 1996) an inverse relationship, and one (Michels et al, 1996) a positive association. The latter was a case-control study nested within the US Nurses' Cohort, which found that the odds of breast cancer for women who weighed 4 kg or more at birth was twice that of women who weighed less than 2.5 kg (Michels et al, 1996). The relationship was strongest for women aged 50 or younger.Various factors might explain the inconsistency of these results. In some studies the information on birthweight was based on recall by the women themselves or their mothers (Michels et al, 1996;Sanderson et al, 1996), in most no account was taken of adult-life risk factors for breast cancer (Ekbom et al, 1992;Le Marchand et al, 1988), and no account was taken in any of childhood and pubertal factors.The present study examines the relationship between birthweight and breast cancer in a UK national cohort of 2221 women who have been followed since their birth in 1946, and for whom data on birthweight, markers of childhood growth and adult-life risk factors for breast cancer have been recorded. The Medical Research Council National Survey of Health and Development (NSHD) is a socially stratified birth cohort of 2548 women and 2814 men born in the UK during the week 3-9 March 1946 (Wadsworth, 1991;Wadsworth and Kuh, 1997). The cohort comprised single, legitimate births to wives of all non-manual and agricultural workers and to 1 in 4 wives of manual workers. There have been 19 follow-up contacts with the cohort members between their birth and age 43 years, most by home interviews. The sample interviewed at age 43 years were, in most respects, representative of the native population of that age (Wadsworth et al, 1992). Since 1993, when the cohort members were 48 years of age, a postal health questionnaire has been sent annually to all women in the study with whom there was still direct contact. At these separate contacts, breast cancer diagnosis was self-reported and recorded. In 1971, when the National Health Service Central Register (NHSCR) started to record cancers occurring in the population of the UK, all cohort members (including those with whom there was no longer direct contact) were 'flagged' at the NHSCR. This provided notification of registrations of cancer, death and emigration for the cohort.Information on birthweight was extracted from the birth records of the cohort members and categorized into four groups: < 3.000 kg, 3.000-3.499 kg, 3.500-3.999 kg, ≥ 4.000 kg, in accord with previous studies (Ekbom et al, 1997;Michels et al, 1996). Data on maternal age and birth order were collected at the original h...

Summary Thyroid cancer incidence has been increasing in many countries, whereas mortality has been falling due to better survival. Radiation is the best-established risk factor and there has been concern that recent rises in incidence might be related to fallout radiation from atmospheric nuclear weapon tests. We examined thyroid cancer time trends and geographical distribution in England and Wales and possible interpretations of these.During Thyroid cancer incidence is increasing in many countries (Pettersson et al., 1991;Weiss, 1979). Exposure to radiation is the main established risk factor. In the USA, the increase in incidence has been associated with widespread use of X-ray therapy for benign conditions of the head and neck among infants and children (deGroot & Paloyan, 1973; Favus et al., 1976;Pottern et al., 1980). Risk is also raised in survivors of the atom bombs of Hiroshima and Nagasaki (Socolow et al., 1963) and populations accidentally exposed to high levels of fresh fission products from nuclear bomb emplosions (Conard et al., 1970). Since nuclear weapon tests release radioactive iodine into the atmosphere, there has been concern that they may have carcinogenic effects on the thyroid (Campbell & Doll, 1963).The risk of thyroid cancer has also been found increased in patients with a history of goitre and other benign thyroid disorders (Preston-Martin et al., 1987;Ron et al., 1987) (ICD7: 194; (WHO, 1957;1967;1977)

Summary Reproductive-related factors play a major role in the aetiology of cancers of the breast, ovary and endometrium. Pregnancy history influences the risk of each of these cancers, and oral contraceptive use modifies the risks of ovarian and endometrial cancers, although its effect on breast cancer risk is less certain. We analysed recent time trends in the incidence and mortality of these cancers in England and Wales and assessed whether they can be explained by changes in fertility and oral contraceptive use. During 1962-87, there were significant increases in the overall incidence of breast cancer (0.95% increase per annum) and ovarian cancer (0.76% per annum) but little increase in endometrial cancer (0.13% per annum). At young ages incidence of each of the cancers has declined in recent years, whereas at older ages there have been substantial increases. Mortality data show similar time trends. In analyses by birth cohort, incidence of each of the cancers increased steeply for successive cohorts born before the turn of the century, and more slowly for cohorts thereafter, reaching a maximum for those born in the 1920s, and decreased for those born subsequently. The increases in incidence for women born before the turn of the century paralleled marked declines in their fertility. The fall in risk for women born after the 1920s was not accompanied by significant increases in their fertility, but coincided with the introduction and increase in use of oral contraceptives. For ovarian and endometrial cancers this accords with strong evidence from person-based studies of the protective effect of oral contraceptives. For breast cancer, the reasons for the recent decline are not clear. It would accord with recent suggestions of a long-term protective effect of oral contraceptives, on which further studies are needed. It is also possible, however, that changes in other risk factors such as dietary fat intake and menarcheal age might have contributed to the recent declines in the risk of these cancers.

The effect of changes in recording and coding of cause of death on trends in cancer mortality in England and Wales in persons aged 45 and over during 1970-1990 is reviewed. During this period, all-cancer mortality rates increased only at ages over 75 in males and over 55 in females. Rises in cancer mortality were largely due to increases in cancer of lung, prostate and unspecified site in men, and of lung, breast and unspecified site in women. Death coding and certification artefacts were much larger in older persons. In those aged 75-84, a change in the position of recording cancer on the death certificate could potentially account for 46% of the recorded increase in prostate-cancer mortality and 28% of the increase in breast-cancer mortality. The decrease in recorded mortality from ill-defined terminal events was far greater than the increase in cancer mortality in this age group. The rise in all-cancer mortality in the elderly was partly due to an increase in lung-cancer mortality, and data artefacts explained a large proportion of the increase in the other common specified cancers in those aged 75-84. The use of routine mortality statistics to chart progress against cancer lacks validity at older ages because of imprecision in certification of cause of death.

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.