A J Swerdlow

Publications of A J Swerdlow

• The Breakthrough Generations Study: design of a long-term UK cohort study to investigate breast cancer aetiology.

  Authors: A J Swerdlow, M E Jones, M J Schoemaker, J Hemming, D Thomas, J Williamson, A Ashworth

  British journal of cancer. 09/2011; 105(7):911-7.

  The rationale, design, recruitment and follow-up methods are described for the Breakthrough Generations Study, a UK cohort study started in 2003, targeted at investigation of breast cancerThe rationale, design, recruitment and follow-up methods are described for the Breakthrough Generations Study, a UK cohort study started in 2003, targeted at investigation of breast cancer aetiology. Cohort members have been recruited by a participant referral method intended to assemble economically a large general population cohort from whom detailed questionnaire information and blood samples can be obtained repeatedly over decades, with high completeness of follow-up and inclusion of large numbers of related individuals. 'First-generation' recruits were women contacted directly, or who volunteered directly, to join the study. They nominated female friends and family, whom we contacted, and those who joined ('second generation') nominated others, reiterated for up to 28 generations. The method has successfully been used during 2003-2011 to recruit 112,049 motivated participants with a broad geographic and socioeconomic distribution, aged 16-102 years, who have completed detailed questionnaires; 92% of the participants gave blood samples at recruitment. When eligible, 2½ years after recruitment, >98% completed the first follow-up questionnaire. Thirty percent are first-degree relatives of other study members. The 'generational' recruitment method has enabled recruitment of a large cohort who appear to have the commitment to enable long-term continuing data and sample collection, to investigate the effects of changing endogenous and exogenous factors on cancer risk.

• Determinants of age at menarche in the UK: analyses from the Breakthrough Generations Study.

  Authors: D H Morris, M E Jones, M J Schoemaker, A Ashworth, A J Swerdlow

  British journal of cancer. 11/2010; 103(11):1760-4.

  Early menarche increases breast cancer risk but, aside from weight, information on its determinants is limited. Age at menarche data were collected retrospectively by questionnaire from 81,606 womenEarly menarche increases breast cancer risk but, aside from weight, information on its determinants is limited. Age at menarche data were collected retrospectively by questionnaire from 81,606 women aged 16-98, resident in the UK and participating in the Breakthrough Generations Study. Menarche occurred earlier in women who had a low birthweight (P(trend)<0.001), were singletons (P<0.001), had prenatal exposure to pre-eclampsia (P<0.001) or maternal smoking (P=0.01), were not breastfed (P(trend)=0.03), were non-white (P<0.001), were heavy (P(trend)<0.001) or tall (P(trend)<0.001) compared with their peers at age 7 and exercised little as a child (P(trend)<0.001). Menarcheal age increased with number of siblings (P<0.001) independently of birth order, and had an inverse association with birth order after adjustment for sibship size (P<0.001). In a multivariate model, birthweight, ethnicity, weight, height, exercise, sibship size and birth order remained significant, and maternal age at birth became significant (positive association, P<0.001). Age at menarche was influenced by both pre- and post-natal factors, and these factors may affect breast cancer risk through this route.

• Risk of cervical abnormality after age 50 in women with previously negative smears.

  Authors: R G Blanks, S M Moss, S Addou, D A Coleman, A J Swerdlow

  British journal of cancer. 06/2009;

  There is discussion over the benefit of continuing cervical screening in women over the age of 50 with a history of negative cytology. We aimed to determine the risk of abnormal cytology in suchThere is discussion over the benefit of continuing cervical screening in women over the age of 50 with a history of negative cytology. We aimed to determine the risk of abnormal cytology in such women. Screening history data from 1985 to 2003 were obtained for a cohort of 2 million women from the NHS cervical screening programme from four Health Authorities in England. The 57 651 women in the cohort who reached age 40 between 1 January 1985 and 31 December 1990 and had at least one routine or opportunistic smear between ages 50 and 54 were included in the analysis. Exposure groups (negative cytology history, negative but including inadequate smears, and positive history) were defined on the basis of screening histories from ages 40 to 49. Sixty-four percent (134/206) (95% CI: 57-71%) of the moderate dyskaryosis or worse lesions at ages over 50 were detected from women in the negative smear history group. After allowance for time since last negative smear, the relative risk for the first primary smear over the age of 50 having moderate dyskaryosis or worse decreased from 0.60 (95% CI: 0.41-0.84) for two negative smear episodes to 0.25 (95% CI: 0.10-0.56) for four negative smear episodes, compared with the positive history group. If screening were discontinued for all women over 50 with a negative history, the majority of cytological abnormalities now being detected at these ages that lead directly to referral to colposcopy would be missed.British Journal of Cancer advance online publication, 5 May 2009; doi:10.1038/sj.bjc.6605069 www.bjcancer.com.

• The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme.

  Authors: R G Blanks, S M Moss, D A Coleman, S Addou, A J Swerdlow

  Cytopathology : official journal of the British Society for Clinical Cytology. 02/2009;

  R. G. Blanks, S. M. Moss, D. A. Coleman, S. Addou and A. J. Swerdlow The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical ScreeningR. G. Blanks, S. M. Moss, D. A. Coleman, S. Addou and A. J. Swerdlow The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening ProgrammeObjective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women's screening histories as episodes rather than as individual smears. Design: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. Setting: NHS Cervical Screening Programme. Population: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. Methods: Cytology information obtained from the call/recall ('Exeter') computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. Main outcome measures: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. Results: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20-24 years down to 0.9% in women aged 60-64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. Conclusion: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.

• Cancer risk in patients with constitutional chromosome deletions: a nationwide British cohort study.

  Authors: A J Swerdlow, M J Schoemaker, C D Higgins, A F Wright, P A Jacobs

  British journal of cancer. 07/2008; 98(12):1929-33.

  The finding of increased risks of specific cancers in individuals with constitutional deletions of chromosomes 11p and 13q led to the discovery of cancer predisposition genes at these locations, butThe finding of increased risks of specific cancers in individuals with constitutional deletions of chromosomes 11p and 13q led to the discovery of cancer predisposition genes at these locations, but there have been no systematic studies of cancer risks in patients with constitutional deletions, across the chromosome complement. Therefore, we assessed cancer incidence in comparison with national cancer incidence rates in a follow-up of 2561 patients with constitutional autosomal chromosome deletions diagnosed by microscopy or fluorescence in situ hybridisation in Britain during the period 1965-2002. Thirty cancers other than non-melanoma skin cancer occurred in the cohort (standardised incidence ratio (SIR)=2.4, 95% confidence interval (CI) 1.6-3.5). There were significantly increased risks of renal cancer in persons with 11p deletions (SIR=1869, 95% CI 751-3850; P=4 x 10(-21)), eye cancer with 13q deletions (SIR=1084, 95% CI 295-2775; P=2 x 10(-11)), and anogenital cancer with 11q deletions (SIR=305, 95% CI 63-890; P=3 x 10(-7)); all the three latter cancers were in the 11 subjects with 11q24 deletions. The results strongly suggest that in addition to suppressor genes relating to Wilms' tumour risk on 11p and retinoblastoma on 13q, there are suppressor genes around 11q24 that greatly affect anogenital cancer risk.

• An examination of the role of opportunistic smear taking in the NHS cervical screening programme using data from the CSEU cervical screening cohort study.

  Authors: R G Blanks, S M Moss, D A Coleman, A J Swerdlow

  BJOG : an international journal of obstetrics and gynaecology. 12/2007; 114(11):1408-13.

  OBJECTIVE: The objective of this study was to study the prevalence of opportunistic smear taking in the NHS cervical screening programme between 1999 and 2003 and the relationship of this toOBJECTIVE: The objective of this study was to study the prevalence of opportunistic smear taking in the NHS cervical screening programme between 1999 and 2003 and the relationship of this to screening interval policy. DESIGN: A cohort study of nearly 2 million women, with data on screening at ages 20-64 years from 1988 to 2003 has been constructed. Data from 1999 to 2003 have been used in this analysis. Screening episodes have been divided into those where the primary smear was initiated by the national call/recall system (invitational), normally at 3- or 5-yearly intervals, and those initiated by the GP or woman (opportunistic). Opportunistic smears were further classified as routine (occurring within 6 months of 3 or 5 years) or sporadic (occurring at other times). SETTING: NHS cervical screening programme. POPULATION: Four Health Authorities in England (now Primary Care Trusts) with supplementary studies on national data. METHODS: Screening episodes have been defined. All episodes start with a primary smear defined as being invitational or opportunistic in origin. MAIN OUTCOME MEASURE: Proportion of primary smear that were invitational or opportunistic. RESULTS: In total, 72% of incident screen primary smears were invitational and 28% were opportunistic. The proportion of opportunistic primary smears was 17 and 43% in 3- or 5-yearly screening policy areas, respectively, resulting in a considerably reduced average screening interval for women aged 20-64 years in 5-year policy areas. CONCLUSION: The NHS cervical screening programme is strongly influenced by opportunistic smear taking. In particular, nominally 5-year policy areas experienced much higher levels of opportunistic smear taking than those with a 3-year policy, causing the average interval in the 5-year areas to be much shorter than the policy would suggest. In future, with the change in national policy for inviting women aged 25-49 years every 3 years and those aged 50-64 years every 5 years, the level of opportunistic smear taking, particularly in the older group of women, needs to be carefully monitored. A lack of compliance may result in greater than predicted costs with little or no additional cancer prevention.

• Ovarian cancer risk in premenopausal and perimenopausal women treated with Tamoxifen: a case-control study.

  Authors: A J Swerdlow, M E Jones

  British journal of cancer. 04/2007; 96(5):850-5.

  As tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increaseAs tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increase ovarian cancer risk in women treated premenopausally. In a national case-control study in Britain, treatment histories were collected for 158 cases of ovarian cancer after breast cancer diagnosed at ages under 55 years and 464 controls who had breast cancer at these ages without subsequent ovarian cancer. Risk of ovarian cancer was not raised for women overall who had taken tamoxifen (odds ratio (OR)=0.9, 95% confidence interval (CI) 0.6-1.3) or for those treated when premenopausal (OR=1.0, 95% CI 0.6-1.6) or perimenopausal (OR=0.7, 95% CI 0.2-2.4). There was also no relation of risk to daily dose, duration or cumulative dose of tamoxifen, or time since last use. There was, however, a significantly raised risk in relation to non-hormonal chemotherapy. The results suggest that tamoxifen treatment of premenopausal or perimenopausal women does not materially affect ovarian cancer risk, but that non-hormonal chemotherapy might increase risk.

• History of allergic disease and risk of meningioma.

  Authors: M J Schoemaker, A J Swerdlow, S J Hepworth, M van Tongeren, K R Muir, P A McKinney

  American journal of epidemiology. 03/2007; 165(5):477-85.

  Epidemiologic studies have consistently shown inverse associations of allergic disease with risk of glioma, but it is unclear whether this association also applies to meningioma. The authorsEpidemiologic studies have consistently shown inverse associations of allergic disease with risk of glioma, but it is unclear whether this association also applies to meningioma. The authors conducted a pooled analysis of meningioma risk in relation to a history of allergic disease based on data from two population-based, case-control studies with 475 cases and 1,716 controls in the United Kingdom (2001-2004). Meningioma risk was significantly reduced in relation to self-reported, physician-diagnosed allergic disease (odds ratio = 0.76, 95% confidence interval (CI): 0.61, 0.96) but was nonsignificantly reduced for individual conditions: asthma (odds ratio = 0.85, 95% CI: 0.61, 1.18), hay fever (odds ratio = 0.81, 95% CI: 0.62, 1.06), and eczema (odds ratio = 0.72, 95% CI: 0.51, 1.02). Risk reductions were greatest for asthma (odds ratio = 0.43, 95% CI: 0.21, 0.89) and hay fever (odds ratio = 0.50, 95% CI: 0.25, 1.00) with an early age at onset (<10 years) and for eczema (odds ratio = 0.46, 95% CI: 0.21, 1.07) with an onset at ages 10-19 years; they were near unity for onset in adulthood. This study suggests an inverse association between a history of allergies and meningioma risk, but with smaller risk reductions than for glioma. The reasons for this association need clarification, as well as an etiologic explanation. Consideration also needs to be given to confounding or bias.

• Medical history, cigarette smoking and risk of acoustic neuroma: an international case-control study.

  Authors: M J Schoemaker, A J Swerdlow, A Auvinen, H C Christensen, M Feychting, C Johansen, L Klaeboe, S Lönn, T Salminen, T Tynes

  International journal of cancer. Journal international du cancer. 02/2007; 120(1):103-10.

  Acoustic neuroma (vestibular schwannoma) is a benign tumor of the vestibulocochlear nerve. Its recorded incidence is increasing but risk factors for this tumor have scarcely been investigated. WeAcoustic neuroma (vestibular schwannoma) is a benign tumor of the vestibulocochlear nerve. Its recorded incidence is increasing but risk factors for this tumor have scarcely been investigated. We conducted a population-based case-control study of risk factors for acoustic neuroma in the UK and Nordic countries, including 563 cases and 2,703 controls. Tumor risk was analyzed in relation to medical history and cigarette smoking. Risk of acoustic neuroma was significantly raised in parous compared with nulliparous women (OR = 1.7, 95% CI: 1.1-2.6), but was not related to age at first birth or number of children. Risk was not associated with a history of allergic disease, past head injury, past diagnosis of a neoplasm or birth characteristics, but was significantly raised for past diagnosis of epilepsy (OR = 2.5, 95% CI: 1.3-4.9). Tumor risk was significantly reduced in subjects who had ever regularly smoked cigarettes (OR = 0.7, 95% CI: 0.6-0.9), but the reduction applied only to current smokers (OR = 0.5, 95% CI: 0.4-0.6), not ex-smokers (OR = 1.0, 95% CI: 0.8-1.3). The reduced risk of acoustic neuroma in smokers and raised risk in parous women might relate to sex hormone levels, or smoking might suppress tumor growth, but effects of parity and smoking on timing of diagnosis of the tumor are also a potential explanation. The raised risk in relation to past diagnosis of epilepsy might be a surveillance artefact or imply that epilepsy and/or antiepileptic medication use predispose to acoustic neuroma. These findings need replication by other studies and possible mechanisms need to be clarified.

• Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries.

  Authors: M J Schoemaker, A J Swerdlow, A Ahlbom, A Auvinen, K G Blaasaas, E Cardis, H Collatz Christensen, M Feychting, S J Hepworth, C Johansen, L Klaeboe, S Lönn, P A McKinney, K Muir, J Raitanen, T Salminen, J Thomsen, T Tynes

  British journal of cancer. 11/2005; 93(7):842-8.

  There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of theThere is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case-control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7-1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR = 1.8, 95% CI: 1.1-3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out.

• Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study.

  Authors: A J Swerdlow, S P Laing, Z Qiao, S D Slater, A C Burden, J L Botha, N R Waugh, A D Morris, W Gatling, E A Gale, C C Patterson, H Keen

  British journal of cancer. 07/2005; 92(11):2070-5.

  Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients withRaised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30-49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22-3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45-5.19), with greatest risks for those with diabetes diagnosed at ages 10-19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

• Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95.

  Authors: I dos Santos Silva, C Higgins, A J Swerdlow, S P Laing, S D Slater, D W M Pearson, A D Morris

  Diabetic medicine : a journal of the British Diabetic Association. 04/2005; 22(4):440-7.

  AIMS: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus. METHODS: Data aboutAIMS: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus. METHODS: Data about diabetes from the Diabetes UK cohort were linked to data on births from the Scottish Hospital In-Patient Record System. This identified 1112 eligible singleton deliveries during 1979-95 to 706 insulin-treated women. RESULTS: One thousand and eighty-four (97.5%) deliveries resulted in a live-born infant and 28 (2.5%) in a stillbirth. There were 13 (1.2%) neonatal deaths. The mean birthweight of the live-born infants was 3421 g, 1.06 standard deviations greater than that of infants in the Scottish general population after correcting for sex and gestational age. Forty-three per cent of live-born babies in the study were large (> Scottish 90th percentile) and 4% small (< 10th percentile) for their sex and gestational age. Macrosomia, defined as birthweight > or = 4000 g, occurred in 23% live-born babies and its prevalence was significantly inversely related to duration of maternal diabetes. However, the mean birthweight of infants born to mothers with diabetes for 20 or more years was still 0.90 standard deviations greater than in the general population. Prevalence of macrosomia increased with increasing number of previous pregnancies, but was not associated with maternal height or smoking habits. Stillbirth and neonatal death rates were, respectively, 4.7 (95% confidence interval = 3.3, 6.8) and 2.4 (1.4, 4.1), times higher than those in the general population. CONCLUSIONS: The frequency of adverse pregnancy outcomes in women with pre-existing insulin-treated diabetes was much higher than in the Scottish general population, and changed little during the study period. A detailed quantification of the independent effect of duration of mother's diabetes on birthweight revealed a continuous inverse correlation between these two variables.

• Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study.

  Authors: A J Swerdlow, S P Laing, I dos Santos Silva, S D Slater, A C Burden, J L Botha, N R Waugh, A D Morris, W Gatling, P J Bingley, C C Patterson, Z Qiao, H Keen

  Diabetic medicine : a journal of the British Diabetic Association. 09/2004; 21(8):845-51.

  AIMS: To investigate mortality in South Asian patients with insulin-treated diabetes and compare it with mortality in non South Asian patients and in the general population. METHODS: A prospectiveAIMS: To investigate mortality in South Asian patients with insulin-treated diabetes and compare it with mortality in non South Asian patients and in the general population. METHODS: A prospective cohort study was conducted of 828 South Asian and 27 962 non South Asian patients in the UK with insulin-treated diabetes diagnosed at ages under 50 years. The patients were followed for up to 28 years. Ethnicity was determined by analysis of names. Standardized mortality ratios (SMRs) were calculated, comparing mortality in the cohort with expectations from the mortality experience of the general population. RESULTS: SMRs were significantly raised in both groups of patients, particularly the South Asians, and especially in women and subjects with diabetes onset at a young age. The SMRs for South Asian patients diagnosed under age 30 years were 3.9 (95% CI 2.0-6.9) in men and 10.1 (5.6-16.6) in women, and in the corresponding non South Asians were 2.7 (2.6-2.9) and 4.0 (3.6-4.3), respectively. The SMR in women was highly significantly greater in South Asians than non South Asians. The mortality in the young-onset patients was due to several causes, while that in the patients diagnosed at ages 30-49 was largely due to cardiovascular disease, which accounted for 70% of deaths in South Asian males and 73% in females. CONCLUSIONS: South Asian patients with insulin-treated diabetes suffer an exceptionally high mortality. Clarification of the full reasons for this mortality are needed, as are measures to reduce levels of known cardiovascular disease risk factors in these patients.

• Second primary breast cancer after Hodgkin's disease.

  Authors: A Horwich, A J Swerdlow

  British journal of cancer. 02/2004; 90(2):294-8.

  Although the potential carcinogenic risk of radiotherapy is well known, it has become clear that there is a particularly high risk of radiation-induced breast cancer in women treated for Hodgkin'sAlthough the potential carcinogenic risk of radiotherapy is well known, it has become clear that there is a particularly high risk of radiation-induced breast cancer in women treated for Hodgkin's disease at young ages. Thankfully, death from breast cancer in this population is uncommon, but it is important to understand factors contributing to the risk, including treatment parameters, and to develop a logical and efficient method for medical management of those at risk. In this minireview, we examine the evidence which should inform such a management policy.

• Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone.

  Authors: A J Swerdlow, C D Higgins, P Adlard, M E Jones, M A Preece

  Neurology. 10/2003; 61(6):783-91.

  OBJECTIVE: To investigate risk factors for Creutzfeldt-Jakob disease (CJD) in patients in the United Kingdom treated with human pituitary growth hormone (hGH). METHODS: Incidence rates of CJD, basedOBJECTIVE: To investigate risk factors for Creutzfeldt-Jakob disease (CJD) in patients in the United Kingdom treated with human pituitary growth hormone (hGH). METHODS: Incidence rates of CJD, based on person-year denominators, were assessed in a cohort of 1,848 patients treated with hGH in the United Kingdom from 1959 through 1985 and followed to the end of 2000. RESULTS: CJD developed in 38 patients. Risk of CJD was significantly increased by treatment with hGH prepared by the Wilhelmi method of extraction from human pituitaries. Risk was further raised if this treatment was administered at ages 8 to 10 years. The peak risk of CJD was estimated to occur 20 years after first exposure, and the estimated lifetime cumulative risk of CJD in Wilhelmi-treated patients was 4.5%. CONCLUSIONS: Size-exclusion chromatography, used in non-Wilhelmi preparation methods, may prevent CJD infection. Susceptibility to CJD may vary with age, and susceptibility may be present in only a few percent of the population.

• Life-course body size and perimenopausal mammographic parenchymal patterns in the MRC 1946 British birth cohort.

  Authors: V A McCormack, I dos Santos Silva, B L De Stavola, N Perry, S Vinnicombe, A J Swerdlow, R Hardy, D Kuh

  British journal of cancer. 09/2003; 89(5):852-9.

  Dense mammographic parenchymal patterns are associated with an increased risk of breast cancer. Certain features of body size have been found to be associated with breast cancer risk, but less isDense mammographic parenchymal patterns are associated with an increased risk of breast cancer. Certain features of body size have been found to be associated with breast cancer risk, but less is known about their relation to breast density. We investigated the association of birth size, childhood growth and life-course changes in body size with Wolfe grade in 1298 perimenopausal women from a British cohort of women born in 1946. The cohort benefits from repeated measures of body size in childhood and adulthood. We obtained mammograms for 90% of women who at age 53 years reported having previously had a mammogram. We found no associations with birth weight or maximum attained height. Body mass index (BMI) at age 53 years and breast size were independently and inversely associated with Wolfe grade (P-value for trend <0.001 for both). Women who reached puberty later were at a greater odds of a higher Wolfe grade than women who had an earlier puberty (odds ratio associated with a 1 year delay in menarche 1.14, 95% CI: 1.01-1.27, adjusted for BMI and breast size at mammography). A higher BMI at any age during childhood or adult life was associated with a reduction in the odds of a higher Wolfe grade, after controlling for breast size and BMI at mammography, for example, standardised odds ratio for height at age 7 was 0.72 (95% CI: 0.64, 0.81). These findings reveal the importance of taking life-course changes in body size, and not just contemporaneous measures, into account when using mammographic density as an intermediate marker for risk of breast cancer.

• Epidemiology of Hodgkin's disease and non-Hodgkin's lymphoma.

  Authors: A J Swerdlow

  European journal of nuclear medicine and molecular imaging. 07/2003; 30 Suppl 1:S3-12.

  This review considers in detail the descriptive and aetiological epidemiology of Hodgkin's disease and non-Hodgkin's lymphoma (NHL), with attention to histological subcategories when the literatureThis review considers in detail the descriptive and aetiological epidemiology of Hodgkin's disease and non-Hodgkin's lymphoma (NHL), with attention to histological subcategories when the literature allows. The aetiology of Hodgkin's disease remains only partially understood. There is evidence that Epstein-Barr virus (EBV) may be involved in the causation of some cases, and clinical immune deficiency is a risk factor for a few, but the evidence is not entirely consistent and other factors may also be important in causing the EBV-associated cases of Hodgkin's disease. The cause of EBV-unassociated cases remains obscure. For NHL, although it has been shown that some cases are related to immune deficiency and chronic antigenic stimulation, and especially to EBV in the context of immune deficiency, the causation of the majority of cases remains unknown. The increasing incidence of NHL, other than that related to AIDS, is also essentially unexplained. Epidemiological investigation of the aetiology of NHL and Hodgkin's disease is making steady progress, however, and there remain leads to be followed that may result in a better understanding and hence prevention.

• Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.

  Authors: S P Laing, A J Swerdlow, S D Slater, A C Burden, A Morris, N R Waugh, W Gatling, P J Bingley, C C Patterson

  Diabetologia. 07/2003; 46(6):760-5.

  AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

• Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study.

  Authors: A J Swerdlow, C D Higgins, P Adlard, M A Preece

  Lancet. 08/2002; 360(9329):273-7.

  BACKGROUND: Growth hormone raises serum concentrations of insulin-like growth factor IGF-I, which is mitogenic and antiapoptotic. There is evidence that raised endogenous levels of growth hormone andBACKGROUND: Growth hormone raises serum concentrations of insulin-like growth factor IGF-I, which is mitogenic and antiapoptotic. There is evidence that raised endogenous levels of growth hormone and IGF-I might be associated with increased risk of certain solid cancers, but there have been no data on long-term risks of solid cancers after growth hormone treatment. METHODS: We did a cohort study to investigate cancer incidence and mortality in 1848 patients in the UK who were treated during childhood and early adulthood with human pituitary growth hormone during the period from 1959 to 1985. Patients were followed up for cancer incidence to December, 1995 and for mortality to December, 2000. Risk of cancer in the cohort was compared with that in the general population, controlling for age, sex, and calendar period. FINDINGS: Patients treated with human pituitary growth hormone had significantly raised risks of mortality from cancer overall (standardised mortality ratio 2.8, 95% CI 1.3-5.1; ten cases), colorectal cancer (10.8, 1.3-38.8; two cases), and Hodgkin's disease (11.4, 1.4-41.3; two cases). Incidence of colorectal cancer was also greatly raised (7.9, 1.0-28.7). After exclusion of patients whose original diagnosis rendered them at high risk of cancer, the significance and size of the risks of colorectal cancer incidence and mortality, and of Hodgkin's disease mortality were increased. INTERPRETATION: Although based on small numbers, the risk of colorectal cancer is of some concern and further investigation in other cohorts is needed. We have no evidence as to whether growth hormone in modern dosage regimens is associated with an increased risk of colorectal cancer.

• A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use.

  Authors: M R Karagas, T A Stukel, J Dykes, J Miglionico, M A Greene, M Carey, B Armstrong, J M Elwood, R P Gallagher, A Green, E A Holly, C S Kirkpatrick, T Mack, A Østerlind, S Rosso, A J Swerdlow

  British journal of cancer. 05/2002; 86(7):1085-92.

  Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in womenData regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.