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A cohort of 412 patients first attending a cystic fibrosis (CF) clinic between 1961 and 1989 were followed up to 30 June 1989. The number of malignancies observed in the cohort was compared with the number expected based on the age, sex and calendar-year-specific cancer registration rates for England and Wales. Four CF patients were diagnosed as having malignancies before 30 June 1989. The tumours were: adenocarcinoma of the terminal ileum; adenocarcinoma of the pancreas, testicular teratoma, and B-cell lymphoma. This compares with 0.89 malignancies expected on the basis of rates in England and Wales (Standardised Registration Ratio = 452; 95% confidence interval 122-1150, P = 0.03). The single case of adenocarcinoma of the terminal ileum contrasts with less than 0.001 expected (P = 0.003) and that of the pancreas with 0.007 expected (P = 0.01). A further adenocarcinoma of the pancreas was diagnosed 2 years after the end of the study period. The two cases of pancreatic cancer compare with 0.008 expected (P = 0.0001) during the period to mid 1991. On the basis of the present findings and previous case reports in the literature adenocarcinoma of the pancreas and adenocarcinoma of the terminal ileum may be associated with cystic fibrosis.

For the last 20 years the National Health Service Central Register (NHSCR) has been used as the principal source of follow-up for mortality, and often for cancer incidence, in many cohort and clinical follow-up studies in England and Wales. Completeness of notification of childhood cancer registrations and deaths from the NHSCR was investigated by comparison between cancers and deaths notified to the Childhood Cancer Research Group (CCRG) from this source and notifications received directly from regional cancer registries and the national death registry. Six thousand, seven hundred and seventy-six (91.8%) of 7,379 cancers incident 1971-84, and 588 (95.8%) of 614 deaths occurring 1953-88, were successfully notified. Failures in cancer notification occurred mainly between the regional cancer registries and the National Cancer Register (3.3%), and between the National Cancer Register and the NHSCR (3.0%). An additional 1.9% of cancer notifications failed between the NHSCR and the CCRG. Incompleteness of registration of childhood cancers by regional cancer registries was estimated to be 4.7%. A total of 12.5% of incident childhood cancers were not notified by NHSCR. Incompleteness of notification may be greater for adults, for whom registration and record linkage may be more difficult. Failures in death notifications occurred mostly because deaths entered on the NHSCR were not notified to the CCRG (3.3%). This incompleteness of notification needs to be taken into account in the interpretation of published studies and in the analysis of studies using NHSCR flagging. It also implies similar incompleteness in published national cancer survival data, which use the same system of flagging. Nevertheless it is a notable achievement that NHSCR has successfully monitored such a high proportion of a population of 50 million people, by entirely clerical procedures, for 40 years.

Skin types 1 and 2, increased numbers of moles, and excessive intermittent sun exposure are known risk factors for cutaneous melanoma, but the inter-relationship between UV radiation exposure, moles and melanoma remains unclear. There is a noteworthy site variation in melanoma, it being more common on the lower leg in women and on the back in men. In order to determine whether this site variation could provide further clues to the pathogenesis of melanoma, we examined site variation in photosensitivity and its relationship to other known melanoma risk factors (number of moles, skin type and skin colour) in 25 healthy volunteers. A marked site variation in photosensitivity was found. The pale skin of the volar aspect of the forearm was markedly less photosensitive than the darker skin of the back. Females were more photoresistant than males on the lower legs even though this is the more common site for melanoma in women. There was some correlation between the number of moles and photosensitivity at the two sites.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin9s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin9s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin9s disease and of second primary non-Hodgkin9s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin9s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin9s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin9s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin9s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin9s disease.

Background: Assessing trends in cancer provides a means for gauging progress against the disease, estimating future demands for care and treatment, and suggesting clues about shifting causal factors that may account for the more recent changes. Purpose: This study was designed to evaluate trends in the major sites of cancer associated with high mortality rates in 15 industrialized countries. To highlight differences among regions, we grouped these countries into six geographic areas: United States, Eastern Europe, Western Europe, East Asia, Oceania, and Nordic countries. In addition, cancer mortality trends in these regions were compared with incidence patterns in the United States. Methods: Data provided by the World Health Organization were used to evaluate age-specific mortality trends from 1969 through 1986 for lung, breast, prostate, stomach, and colorectal cancers and for all other sites considered as a group. We also assembled and analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the same sites and age groups from 1973 through 1986. Results: Over the period 1969 through 1986, recorded cancer mortality in persons aged 45 years and older in the six regions studied has increased for lung, breast, and prostate cancers in most age groups, while the decline in stomach cancer mortality is substantial. The increase in lung cancer deaths in men aged 45-54 years has slowed greatly or reversed in all areas except Eastern Europe and East Asia. Trends for intestinal cancer vary by age and region. For all other sites considered as a group, increases have occurred for persons older than 64 years in most regions. In Eastern Europe, there are disturbingly high rates and rapid increases for several of the major forms of cancer in persons aged 45-54 years. In general, trends for cancer incidence in the United States parallel those for mortality. For intestinal cancer, however, incidence has increased while mortality has declined. Conclusions: The trends we report cannot be explained solely by changes in cigarette smoking or aging. Other causes of changes in cancer incidence and mortality need to be determined. Implications: The increasing and decreasing trends in mortality from and incidence of cancer that we found are important for health care planning and may also suggest opportunities for research in cancer prevention. [J Natl Cancer Inst 84: 313-320, 1992]

Dr Milham and Mr Morgan are concerned about the age and gender distribution of controls relative to the cases in our recent paper. In short, the control series in the Interphone study was not selected for meningioma cases only, but the age and sex distribution reflect that of the entire set of cases including also cases of glioma and acoustic neurinoma. All controls were included in the analysis of meningioma in order to increase the statistical power. The age and sex distribution have no influence on the results of the stratified (conditional) analysis. Secondly, Dr Milham points out that dissimilar case and control frequencies are given in different sections of the paper. This refers to numbers of eligible, participating and analysed cases and controls. Indeed, it would be ideal that all eligible subjects would participate and provide complete information, but this rarely occurs in practice. Thirdly, both find the large number of odds ratios

The epidemiology of germ cell cancer of the ovary has been little investigated. We studied ovarian germ cell cancers incident 1971-84 in England, using data from the England and Wales national cancer register. The age distribution showed a sharp peak at ages 15-19, to which both teratomas and dysgerminomas contributed equally, and a secondary, much wider peak, at ages 65-69, mainly due to teratomas. For teratomas there were diverging secular trends by age: incidence has been increasing at ages 0-44 (P around 0.05) and decreasing at ages over 44 (P less than 0.01). Birth cohort analysis showed an increase in risk at ages 0-44 for more recent generations of women. There were no changes over time for dysgerminomas. There was no clear geographic pattern of distribution across the regions of England. The early age peak, and the increase in incidence of ovarian germ cell cancers at young ages but decrease at older ages, resembles testicular cancer epidemiology. Interestingly, discrepancies and similarities in the age distribution of these tumours between the sexes parallel lifetime profiles of gonadotropin levels in each sex.

OBJECTIVE--To determine whether the risk of Kaposi9s sarcoma in patients with AIDS is increased by sexual contact with groups from abroad with a high incidence of Kaposi9s sarcoma. DESIGN--Analysis of risk of Kaposi9s sarcoma in patients with AIDS, according to country of origin of their sexual partners. SETTING--United Kingdom. PATIENTS--2830 patients with AIDS reported to the Communicable Disease Surveillance Centre and the Communicable Disease (Scotland) Unit up to March 1990, of whom 566 had Kaposi9s sarcoma. MAIN OUTCOME MEASURES--Percentage of patients with AIDS who had Kaposi9s sarcoma. RESULTS--537 of 2291 homosexual or bisexual men (23%) with AIDS had Kaposi9s sarcoma; 10% (14/135) of the men and women who acquired HIV by heterosexual contact had Kaposi9s sarcoma. None of the 316 subjects who acquired HIV through non-sexual routes had Kaposi9s sarcoma. Kaposi9s sarcoma was more common among homosexual men whose likely source of infection included the United States (171/551, 31%) or Africa (9/34, 26%) than among those infected in the United Kingdom (119/625, 19%) (p less than 0.05). CONCLUSION--The data suggest that Kaposi9s sarcoma is caused by a sexually transmissible agent which was introduced into the British homosexual population mainly from the United States [corrected].

Mortality and cancer incidence were analysed in follow-up of a cohort of 3327 Vietnamese refugees who came to Britain after the end of the Vietnam war. Overall mortality of the refugees was very low compared to expectations based on England and Wales national rates: the all-cause standardized mortality ratio for males was 64 (95% confidence interval 52-77) and for females was 56 (95% confidence interval 44-71). This resulted particularly from very low mortality from ischaemic heart disease and colorectal cancer in each sex, and breast cancer in women. Mortality in the refugees was greatly increased for tuberculosis, cancer of the stomach in both sexes, cancers of the nasopharynx and liver in males, and peptic ulcer in females. Cancer incidence data showed in addition an excess of cancer of the penis. Despite the great trauma and stress of their flight, the only indication of a possible effect of the migration on the mortality of the refugees who survived to reach Britain was the excess of peptic ulcer deaths in women.

Melanocytic naevi (MN) are recognised risk factors for malignant melanoma but the epidemiology of MN is poorly understood. Some MN are present at birth and the study of congenital lesions is an important first step toward understanding the development of MN in early life. In this study, the prevalence and characteristics of congenital pigmented lesions were documented in 1012 White caucasian newborn babies at a maternity hospital in Oxford. Only 12 babies (1.2%) were found to have pigmented skin marks and each of these had only one lesion and no other abnormalities. MN were identified with certainty in only five babies (0.5% of the population; 95% CI, 0.06%-0.93%) thus confirming the relatively low prevalence of this lesion. Four of the MN were noted to be 'small' (less than 15 mm diameter) and all five were less than or equal to 20 mm in diameter. In other respects, the MN displayed a diversity of features. Of the other lesions there were two Mongolian blue spots, one melanocytic pustule, one 'probable' MN and three unusual skin marks where the diagnosis was uncertain but considered unlikely to be MN. During the course of the study, examinations were also carried out incidentally on 39 non-White babies. Twenty-two of these were noted to have Mongolian spots (57%) and three had other pigmented lesions (8%).

Objective: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes. Design: Cohort study. Setting: Hospital for Sick Children, Great Ormond Street, London. Subjects: 1075 boys with cryptorchidism treated by orchidopexy or hormones at the hospital during 1951-64. Main outcome measures: Relative risk of testicular cancer in the cohort compared with men in the general population. Results: 12 testicular cancers occurred in 11 of the patients during follow up to mid-1990 (relative risk of cancer in males with cryptorchidism=7.5 (95% confidence interval 3.9 to 12.8)). The relative risk fell significantly beyond 15 years after orchidopexy but did not decrease with younger age at orchidopexy. Risk was significantly raised in testes that had had biopsy samples removed during orchidopexy (relative risk=66.7 (23.9 to 143.3) compared with a testis in a man in the general population) and was significantly greater in these testes than in undescended testes that had not had biopsy samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or distinguishing clinical aspects of the testes that had had biopsy samples taken and later developed malignancies were evident in the case notes. No histological abnormalities were evident at initial biopsy except in one testis that had features of dysgenesis. Conclusions: Biopsy seems to be a stronger risk factor for testicular cancer than any factor previously identified. The trauma of open biopsy may contribute substantially to risk of malignancy or the testes may have been selected for biopsy on the basis of clinical factors predictive of malignancy but not mentioned in the case notes. Key messages The reasons for increased risk of testicular cancer in cryptorchidism are unclear Risk of testicular cancer was determined in follow up of 1075 boys with cryptorchidism treated during 1951-64 The relative risk of testicular cancer in the cohort compared with men in the general population was 7.5 and did not decrease with younger age at orchidopexy Risk was much greater in undescended testes from which a biopsy sample had been taken during orchidopexy than in those with no biopsy Biopsy was a stronger risk factor for testicular cancer than any factor previously identified

The Portuguese Thorotrast study cohort consists of a group of patients who received Thorotrast for diagnostic reasons between 1929 and 1956, and a group of similar patients who were given nonradioactive contrast agents. The cohort members were identified from medical records that contained information on reasons for the radiological investigation, type of procedure employed, and name and dose of the contrast medium used. This cohort was assembled in 1961, but its follow-up was interrupted in 1976. We have now reactivated this cohort and extended its follow-up through the end of 1996. Similar methods were used to follow up and ascertain cause of death for the Thorotrast-exposed and unexposed subjects. A total of 1931 patients who received Thorotrast systemically and 2258 unexposed subjects were initially identified from medical records. We were able to successfully follow up 58.6% (1131) of the Thorotrast patients and 45.7% (1032) of the unexposed patients. By the end of 1996, 92.2% of the Thorotrast patients and 75.2% of the unexposed patients were dead. Mortality from all causes was increased in the Thorotrast patients compared to those who were not exposed. This excess in mortality increased with time since exposure, peaking 30 years after administration of Thorotrast. The rise in overall mortality was essentially due to neoplasms [relative risk (RR) adjusted for sex, age and period = 6.04, 95% CI = 4.42-8.26], nonmalignant liver disorders (RR = 5.67, 95% CI 3.13-10.3) and nonmalignant hematological conditions (RR = 14.2, 95% CI = 2.54-79.3). The increase in mortality from neoplasms was explained mainly by increases in the risk of liver cancer (RR = 70.8, 95% CI = 19.9-251.3) and, to a much lesser extent, leukemia (RR = 15.2, 95% CI = 1.28-181.7).

Lung cancer mortality in a cohort of 4320 miners first employed during 1948-1959 at the Jáchymov and Horní Slavkov uranium mines in West Bohemia and followed until 1 January 1991 has been studied to gain a greater understanding of the consequences of exposure to radon and its progeny. Among men whose exposure rates never exceeded 10 working levels, excess relative risks per unit exposure were greater in younger men, and exposures received in the periods 15-24, 25-34 and 35+ years previously were found to have 47, 24 and 0% of the effect of exposures 5-14 years previously. Within this low-exposure-rate group excess relative risk increased linearly with time-weighted cumulative exposure and did not depend on exposure rate or duration of exposure. For men who spent less than 20% of their employment at the Jáchymov mine the excess relative risk per working level month was 1.36% (95% confidence interval 0.52-3.54) in the baseline category (age group 55+ and exposure received 5-14 years previously). For men who spent more than 20% of their employment at Jáchymov, the corresponding excess relative risk per working level month was higher by a factor of 1.80 (95% confidence interval 1.27-2.97). The difference may be due to the fact that men who spent more than 20% of their employment at Jáchymov were exposed to the much higher levels of arsenic in the dust at the Jáchymov mine than at other mines. When men with exposure rates above 10 working levels were included in the analysis, patterns of risk were complex and depended on both exposure rate and duration of exposure in addition to the factors mentioned above. If these findings are confirmed elsewhere, calculation of risk estimates for extrapolation to modern occupational or environmental exposures should be based on miners with exposure rates below about 10 working levels. Further investigation is desirable of the influence of dusts containing arsenic on lung cancer risk in miners exposed to radon.

Exposure to solar radiation is increasingly being associated with a risk of cutaneous melanoma, and some risk has also been attributed to exposure to fluorescent lights. The risk of cutaneous melanoma associated with exposure to some sources of artificial ultraviolet radiation was examined in a case-control study in a Scottish population with fairly low exposure to natural ultraviolet radiation. The risk was not significantly or consistently raised for exposure to fluorescent lights at home or at work. The use of ultraviolet lamps and sunbeds, however, was associated with a significantly increased risk (relative risk = 2.9; 95% confidence interval 1.3 to 6.4), and the risk was significantly related to duration of use. The risk was particularly raised among people who have first used [corrected] ultraviolet beds or lamps more than [corrected] five years before presentation (relative risk = 9.1; 95% confidence intervals 2.0-40.6), in whom it was significantly related to cumulative hours of exposure. The risks associated with exposure to ultraviolet lamps and sunbeds remained significant after adjustment for other risk factors for melanoma.

Incidence of eye cancer in persons 15 years of age and over in England and Wales was studied as a surrogate for eye melanoma data. Age-standardized registration rates for cancer of the eye in adults increased by half in both males and females from 1962 to 1977. This probably reflects a real increase in incidence of eye melanoma. There was a gradient of increasing incidence with decreasingly urban place of residence, but there was no gradient of incidence with latitude. In both sexes, incidence was highest in the Birmingham region. Proportional registration ratios were generally higher for nonmanual than for manual social classes and notably high for electrical and electronics workers.

Mortality and malignancy were studied in a series of 32 patients with xeroderma pigmentosum presenting during the period 1950-84. Twenty-nine of the patients were followed to the end of 1984 using the National Health Service Central Register, and hospital case records and correspondence with referring physicians; three patients had incomplete follow-up. Three of the patients developed malignant melanoma during follow-up, but none developed internal malignancy. Two males and one female died [standardized mortality ratio (SMR) = 971, P less than 0.05, for males; SMR = 1931, not significant, for females]. All three deaths were from non-malignant causes: severe neurological involvement with terminal infection. This high mortality from neurological complications in xeroderma pigmentosum patients contrasts with previously reported mortality, particularly from actinic-induced cutaneous tumours.

The position of the testes reduces their temperature but makes them vulnerable to trauma. Patients with testis cancer frequently report prior testicular trauma, but this trauma may have triggered diagnosis of the tumor rather than been aetiological. In this study, the frequencies of various prior traumatic and temperature exposures in 259 patients with testis cancer were compared with their frequencies in two sets of control patients who did not have testis cancer. Particular effort was made to prevent bias. Testis cancer was not significantly associated with any temperature or trauma exposure and the confidence limits of the findings excluded substantially raised risks. The evidence suggests that raised temperatures and traumas commonly encountered in everyday life are not important risk factors for testis cancer. The possible aetiological roles of extreme trauma sufficient to cause atrophy, and of the trauma and raised temperature which can occur in cryptorchidism, however, need investigation by other methods.

SUMMARY There is growing evidence that individuals at high risk of cutaneous melanoma can be identified by the use of simple measures of benign melanocytic naevi—raised risk occurring in persons who have large numbers of naevi, or naevi with atypical clinical features. Very high risk of melanoma appears to exist in two rare groups: persons with dysplastic naevi whose families include at least two individuals who have had melanoma, and persons with giant congenital naevi. Risks of melanoma in other individuals with dysplastic naevi and in persons with small congenital naevi have not yet been quantified. Much of the published work on risk of melanoma in relation to naevi has been based on clinical series or assemblage of case reports, with great potential for bias. In such studies, naevi have often been classified into dichotomies or syndromes originally defined for pathological or clinical purposes, frequently using poorly reproducible criteria. Case-control and cohort studies of the relationship of naevi to melanoma are needed, which use reproducible criteria and designs minimizing bias, and which examine risk in relation to graded clinical and histological measures of naevi. Malignant melanoma is the commonest cause of skin cancer death and in many white populations is increasing rapidly in incidence and as a cause of mortality. Thus, there is a particular need to nnd aetiological factors and high-risk groups on whom preventive measures could be concentrated. Recent studies have shown that naevus ‘parameters’ (measures or features) are strong predictors of melanoma risk, encouraging interest in naevi and their relationship to melanoma. This paper synthesizes from an epidemiologicat standpoint present evidence and research needs regarding the relation of melanocytic naevi to melanoma.

A case-control study is reported based on 87 deaths from testicular cancer that occurred in children in Great Britain 1953-73. Factors that significantly increased relative risk were tuberculosis of the mother during the index pregnancy and maternal epilepsy; factors that increased risk but not significantly were hyperemesis in the index pregnancy, a maternal history of stillbirths, and hernia and genitourinary defects in the child. Cryptorchidism was not studied. The available evidence suggests that prenatal determinants of testicular cancer in adults are also determinants of testicular cancer in childhood. The incidence and mortality from this disease are not increasing among children in Britain and other countries, whereas there is an increasing trend in young adults in several developed countries. Probably, therefore, the secular increase in the rates of young adult testicular cancer is due to factors that affect adults but not children, the hence are likely to be postnatal.

The month of birth of boys undergoing orchidopexy in the Oxfordshire Health District during the years 1974-83 was analysed. A significant seasonal variation with a peak in April was found for those boys operated upon by paediatric surgeons at a young age (0-4). Possible causes of this variation and its relationship to the aetiology of cryptorchidism are discussed.

For some death certificates in England and Wales the cause information coded and published in national data is not that initially submitted by the certifier, but instead derives from a subsequent enquiry to the certifier for further information. These enquiries can lead to substantial artefacts in secular mortality data, and also to substantial non-comparability between mortality data for special study groups, such as subjects in cohort studies, and published mortality data. A description of current enquiry policy relevant to cancers, and changes in this policy over recent years is given to aid interpretation of mortality data. The effects on secular data of changes in enquiry policy are illustrated. At 4-digit level of the ICD, changes in enquiry policy can alter published mortality rates by several hundred per cent. At 3-digit level the greatest effects of enquiries at present are to increase the number of deaths coded to cancer of the eye by 35% and cancer of the body of the uterus by 31%; cancers of the thymus, heart and mediastinum are increased by 18%, and pleural cancer by 17%, while decreases of more than 10% are caused for several 'other' and 'unspecified' rubrics, and a decrease of 6% for deaths coded to melanoma.

The relation of occupation to the risk of testicular cancer was investigated in a case-control study using data from the files of the South Thames Cancer Registry. Risks by age and histology subdivisions of the tumour were investigated since there is epidemiological evidence of differences in aetiology between these subdivisions but no previous systematic study of occupational risks by age and histology. Analyses were conducted comparing 1605 cases of testicular cancer incident in the region during 1958-77 with 7187 controls selected from other cancers incident in men in the region during the same period. The greatest risks of testicular cancer overall were for administrators and managers, sales workers, professional and allied workers, electrical workers, and clerical workers; these occupations were generally also at high risk of subdivisions of the tumour age and histology. Risk of testicular cancer overall and in each age and histology subgroup was greater in men of high than of low occupation based social class. Occupations with high risk of testicular cancer for their social class are of particular interest for further investigation of possible occupational risk factors; occupations with this characteristic for testicular cancer overall or in subdivisions in the present and some previous data are farmers, electrical workers, and paper and printing workers.

Coronary heart disease (CHD) mortality has declined in Britain since the early 1970s and followed a reduction in dietary fat intake in the population. We attempted to determine whether there have been changes in dietary fat intakes by social classes and to see whether they correspond to social class changes in CHD mortality, where the greatest reduction has been in the upper social class groups. Dietary fat intake was specially obtained by social class on a household basis from the National Food Survey (NFS) for 1974 and 1981. The decline in saturated fat intake and increase in polyunsaturated fat is shown to have occurred in each social class group, although it was not possible to examine the data separately for men and women. In contrast, the decline in the proportion of current smokers between 1974 and 1980 (from the General Household Survey) was greatest in the higher social classes. Rates of CHD mortality showed the greatest decline among men in social classes I & II over the period 1969/73 to 1979/83. However, despite some problems in the interpretation of the data collected by the NFS, this study shows that recent social class trends in dietary fat intakes are unlikely to account for the differential changes in CHD mortality. Changes in the prevalence of smoking among social classes are more consistent with the change in CHD mortality.

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case-control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case-control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r = 0.23, P = 9.3 × 10 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10 ) and concordance in effect direction (P = 2.0 × 10 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases. ispartof: Cancer Medicine vol:7 issue:5 pages:1978-1987 ispartof: location:United States status: published

In a case-control study of testis cancer 259 cases with testicular cancer, 238 controls treated at radiotherapy centres and 251 non-radiotherapy hospital in-patient controls were interviewed about some possible prenatal and familial risk factors for the tumour. For firstborn men, the risk of testis cancer increased significantly according to maternal age at the subject's birth, and this effect was most marked for seminoma. The association with maternal age was not apparent for cases other than firstborn. The risk of testis cancer was also significantly raised for men from small sibships and of early birth order. These results accord with the theory that raised maternal levels of available oestrogen during the early part of pregnancy are aetiological for testicular cancer in the son, although other explanations are possible; there is evidence that seminoma risk may particularly be affected.

The relationship of risk of testis cancer, and subdivisions of the tumour by histology, to variables which may be related to hormonal status, sexual behaviour and fertility was investigated in data from a case-control study with 259 cases and 2 sets of controls. No consistent association was found between testis cancer risk and age at puberty, need to shave, obesity, alcohol intake, animal fat intake, and sexual behaviour. There was a significant excess of seminomas in very tall men. Testis cancer cases showed lower fertility than controls according to various measures, but this reflected the greater frequency of cryptorchidism among cases compared to controls. Among non-cryptorchid subjects there was no clear evidence that infertility was associated with risk of testis cancer.

A case-control study of the aetiology of testicular cancer was conducted using information obtained by interview and from case-notes of 259 cases with testicular cancer and two sets of control patients -238 men with diagnoses other than testicular cancer attending the same radiotherapy centres as those attended by the cases, and 251 hospital in-patients not attending radiotherapy departments. Logistic regression analyses were performed, after stratifying by age and region of residence, to estimate the relative risks (RRs) associated with various aspects of prior medical history. The risk of testicular cancer was found to be raised for men with a history of cryptorchidism (RR based on comparison with all controls = 6.3; P less than 0.001), inguinal hernia (RR = 1.6; P = 0.14), mumps orchitis (RR = 12.7; P = 0.006), atopy (RR = 1.8; P = 0.03), and meningitis (RR = 3.0; P = 0.21). Inguinal herniorrhaphy before the age of 15 years was particularly a risk factor for seminoma, whereas the relative risks were similar for seminoma and teratoma for the other factors. The results add to the growing evidence that congenital abnormalities involving the process of testicular descent and closure of the processus vaginalis are risk factors for testicular cancer, and that some types of testicular damage later in life may also be important. The findings of associations with previous atopy and certain infections suggest a possible second aetiological mechanism - that immunological abnormalities may be associated with an increased risk of testis cancer.

A study of cryptorchidism was undertaken based on patients identified through the Oxford Record Linkage Study. The cumulative lifetime incidence of archidopexy among males in the study area was estimated to be 3.38%; 88% of orchidopexies were performed on males aged 5 years and over and 32% on those aged 10 and over. In a case-control study with 146 cases ascertained at orchidopexy and 146 matched controls there was a substantially increased risk of cryptorchidism for those who had undergone breech labour. Raised risks of cryptorchidism were found for boys born to mothers who were primigravidas or aged under 20, and a significantly reduced risk was found for boys whose mothers were of B blood group. There was a gradient of increasing risk with decreasing birth weight and a significantly raised risk associated with clinical inguinal hernia. Since cryptorchidism and testicular cancer share several risk factors, it may be profitable to study newly identified risk factors for cryptorchidism in relation to testicular cancer.

Examination of 180 patients with cutaneous malignant melanoma and 197 control patients in a case-control study showed that the risk of melanoma is strongly related to numbers of benign melanocytic naevi (moles). Some unusual features of naevi--a diameter exceeding 7 mm, colour variation, and irregular lateral outline--also showed a strong association with the risk of melanoma, but the relation of numbers of naevi to risk was present even in the group of patients whose naevi had none of these unusual features. Biopsy of clinically atypical naevi from several of the patients at highest risk generally did not show dysplastic histology. Thus a group of people at high risk of melanoma may be identified by using simple clinical assessment of naevi.

The seasonality of presentation of 1019 skin melanomas in Oxford Region 1952-1975, and of 1,523 squamous cell and 4,865 basal cell skin cancers in the region 1967-1975, were analysed using data from the Oxford Cancer Registry. For males and for females, for each of the histologies there was a peak of presentations during July to September. In further subdivisions of the data by age and by skin site, a summer or autumn peak was generally present except where numbers of cases were small. Amplitude of seasonality did not show consistent differences by histology, sex, or skin site, but for both melanoma and squamous cell cancer amplitude was greater for persons aged under 55 years than for older persons. There was no substantial seasonality for presentations of cancers of all non-skin sites in the region. The seasonality of presentation of skin cancers appeared not to be mainly an artefact of the cancer registration process or of organisational aspects of medical care attendance, and only a small proportion of it could be explained as an artefact of the longer term increase in registrations of these cancers. The visibility of skin cancers might have lead to seasonal variation in rapidity of presentation to medical care, for instance for social reasons, or the results might reflect a short induction period effect of exposure to a seasonal insult, perhaps sun radiation, on the aetiology, growth or symptoms of skin cancers; for melanoma there is previous evidence suggesting a short induction period aetiological effect of sun radiation.

Data from the England and Wales national congenital malformation notification scheme were examined for associations of male genital tract malformations. For some of the malformations comparison of notification rates with the literature suggested gross undernotification. There was also evidence suggesting bias: examination of the relationships of the malformations to birth weight, maternal parity, and maternal age at delivery showed some highly significant trends in risk, most of which were at variance with findings in the literature, and several potential mechanisms for bias could be adduced. Direct investigation is needed, for this and other similar data sets, of the extent and mechanisms of biased undernotification.

In a study of risk factors for the development of melanocytic naevi in relation to the pathogenesis of malignant melanoma 197 white adults were examined by four dermatologists and naevus counts correlated with several other features. Highly significant associations were found between large numbers of banal acquired melanocytic naevi and the ability to tan easily without burning (skin types 3 and 4; relative risk 4.6), brown or hazel eyes (relative risk 3.5), green or grey eyes (relative risk 3.5) and brown or black hair (relative risk 3.7). No significant associations with numbers of naevi were shown for parity or use of oral contraceptives or other steroid hormones. This is the first study to find any relation between melanocytic naevi and phenotypic factors in a white population.

In most of England and Wales the incidence of malignant melanoma of the skin has risen rapidly in recent years, especially in women. Mean incidences in the 14 English health regions and Wales correlated negatively with latitude and positively with hours of sunshine, suggesting that exposure to sunshine was an important causal factor. Male and female incidences within a region tended to show similar yearly fluctuations, implying a common factor affecting the incidence in both men and women with a short latent period of action. This factor may be exposure to sunshine, which may cause melanoma after an induction period of about two years; for women the incidence of melanoma in the regions of England and Wales correlated positively with hours of sunshine two years earlier.

We present some new analyses of data from the Western Canada Melanoma Study [1–3], based on 595 subjects with melanoma, excluding lentigo, and community controls. The validity of the study has been checked; interviewed patients do not differ from non-interviewed patients in pathological type, stage, or age, and the control group is virtually identical to the census populationon variables where this can be assessed. For many exposures, the proportions of patients and controls giving positive replies are virtually identical, suggesting no major response bias.

Ultrasound tomography (UST) is an emerging whole breast 3D imaging technique that obtains quantitative tomograms of speed of sound (as well as other properties) of the entire breast. The measured parameter is the volume averaged speed of sound (VASS) [1,2]. It improves on mammography by measuring density at each voxel and holds promise as a cheap, patient-acceptable, non-ionising radiation method to evaluate density. This study was to evaluate the technique of UST and compare VASS with percentage water density from non-contrast MRI.

Background Women diagnosed with breast cancer frequently attribute their cancer to psychological stress, but scientific evidence is inconclusive. We investigated whether experienced frequency of stress and adverse life events affect subsequent breast cancer risk. Methods Breast cancer incidence was analysed with respect to stress variables collected at enrolment in a prospective cohort study of 106,000 women in the United Kingdom, with 1783 incident breast cancer cases. Relative risks (RR) were obtained as hazard ratios using Cox proportional hazards models. Results There was no association of breast cancer risk overall with experienced frequency of stress. Risk was reduced for death of a close relative during the 5 years preceding study entry (RR = 0.87, 95 % confidence interval (CI): 0.78–0.97), but not for death of a spouse/partner or close friend, personal illness/injury, or divorce/separation. There was a positive association of divorce with oestrogen-receptor-negative (RR = 1.54, 95 % CI: 1.01–2.34), but not with oestrogen-receptor-positive breast cancer. Risk was raised in women who were under age 20 at the death of their mother (RR = 1.31, 95 % CI: 1.02–1.67), but not of their father, and the effect was attenuated after excluding mothers with breast or ovarian cancer (RR = 1.17, 95 % CI: 0.85–1.61). Conclusions This large prospective study did not show consistent evidence for an association of breast cancer risk with perceived stress levels or adverse life events in the preceding 5 years, or loss of parents during childhood and adolescence. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0733-1) contains supplementary material, which is available to authorized users.