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Whether individuals with autism spectrum disorders (ASDs) have a higher-than-expected risk of cancer remains unknown.We carried out a population-based cohort study including 2.3 million individuals live-born to mothers from Nordic countries during 1987-2013 in Sweden with follow-up through 2016 (up to age 30 years). Individuals with ASD were ascertained through the Swedish National Patient Register. We estimated the relative risk of cancer in relation to ASD by odds ratios (ORs) and associated 95% confidence intervals (CIs) derived from logistic regression, after detailed adjustment for potential confounders. We also carried out a sibling comparison to address familial confounding and a genetic correlation analysis using the genome-wide association study summary statistics to address confounding due to potential polygenetic pleiotropy between ASD and cancer.We observed an overall increased risk of any cancer among individuals with ASD (OR 1.3, 95% CI 1.2-1.5), compared with individuals without ASD. The association for any cancer was primarily noted for narrowly defined autistic disorder (OR 1.7, 95% CI 1.3-2.1) and ASD with comorbid birth defects (OR 2.1, 95% CI 1.5-2.9) or both birth defects and intellectual disability (ID; OR 4.8, 95% CI 3.4-6.6). An association was also suggested for ASD with comorbid ID (OR 1.4; 95% CI 0.9-2.1), but was not statistically significant. ASD alone (i.e. without comorbid ID or birth defects) was not associated with an increased risk of any cancer (OR 1.0, 95% CI 0.8-1.2). Sibling comparison and genetic correlation analysis showed little evidence for familial confounding or confounding due to polygenetic pleiotropy between ASD and cancer.ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring ID and/or birth defects in ASD.

This abstract was withdrawn by the authors. Citation Format: Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O'Brien KM, Adami H-O, Baglietto L, Bernstein L, Bertrand KA, Boutron-Ruault M-C, Chen Y, Connor AE, Dorronsoro M, Dossus L, Eliassen AH, Giles GG, Gram IT, Hankinson SE, Kaaks R, Key TJ, Kirsh VA, Kitahara CM, Koh W-P, Larsson SC, Linet MS, Ma H, Masala G, Merritt MA, Milne RL, Overvad K, Ozasa K, Palmer JR, Riboli E, Rohan TE, Sadakane A, Sund M, Tamimi RM, Trichopoulou A, Ursin G, Van Gils CH, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Yuan J-M, Zeleniuch-Jacquotte A, Sandler DP, Swerdlow AJ. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-01.

The development of nasopharyngeal carcinoma (NPC) and its unique geographic distribution have long been attributed to a combination of dietary intake of salt-preserved fish, inherited susceptibility, and early-life infection with the Epstein-Barr virus (EBV). New findings from our large, rigorously designed, population-based case-control study of NPC in southern China have enabled substantial revision of this causal model. Here, we briefly summarize these results and provide an updated model of the etiology of NPC. Our new research identifies two EBV genetic variants that may be causally involved in the majority of NPC in southern China, and suggests the rise of modern environmental co-factors accompanying cultural and economic transformation in NPC-endemic regions. These discoveries can be translated directly into clinical and public health advances, including improvement of indoor air quality and oral health, development of an EBV vaccine, enhanced screening strategies, and improved risk prediction. Greater understanding of the roles of environmental, genetic, and viral risk factors can reveal the extent to which these agents act independently or jointly on NPC development. The history of NPC research demonstrates how epidemiology can shed light on the interplay of genes, environment, and infections in carcinogenesis, and how this knowledge can be harnessed for cancer prevention and control.

Lung cancer is the most commonly diagnosed cancer among men in most countries, and is the primary cause of cancer death in men and women. Its epidemic increase in incidence began in the first half of the twentieth century, paralleling the uptake of cigarette smoking that occurred 20 years before. A series of landmark studies beginning in 1950 established tobacco as the primary cause of lung cancer. Current smokers have a 10- to 20-fold higher lung cancer risk compared to never smokers. Important for prevention, former smokers substantially reduce this excess risk 5 years after smoking cessation. Exposure to secondhand smoke, a well-established risk factor for lung cancer, has a 20%–25% higher risk for those exposed. There are several occupational exposures associated with lung cancer, including asbestos. Despite the success in defining lung cancer’s etiology, this highly preventable disease remains among the most common and most lethal cancers globally.

This chapter reviews central concepts in epidemiology, which apply also to cancer epidemiology. It examines cohort and case-control studies, with reference also to studies of genetic epidemiology, it considers the impact of chance and systematic errors, and it traces the process of causal reasoning. It attempts to convey that the sometimes esoteric theory of modern epidemiology can be condensed to a few central issues, namely (1) how to quantify and understand the impact of chance; (2) how to best harvest information on exposures and outcomes from a source population by using a cohort design, a case–control design, or variants thereof; (3) how to achieve valid results by minimizing the impact of confounding and bias, and; (4) how to address the central issue of causality in a structured way. A glossary at the end of the chapter provides a summary of definitions.

This chapter explores the genetic epidemiology of cancer: the identification and quantification of inherited genetic factors, and their potential interaction with the environment, in the etiology of cancer in human populations. It also describes the techniques used to identify genetic variants that contribute to cancer susceptibility. It describes the older research methods for identifying the chromosomal localization of high-risk predisposing genes, such as linkage analysis within pedigrees and allele-sharing methods, as it is important to understand the foundations of the field. It also reviews the epidemiologic study designs that can be helpful in identifying low-risk alleles in candidate gene and genome-wide association studies, as well as gene–environment interactions. Finally, it describes some of the genotyping and sequencing platforms commonly employed for high-throughput genome analysis, and the concept of Mendelian randomization and how it may be useful in the study of biomarkers and environmental causes of cancer.

Bladder cancer is the ninth most common cancer worldwide, resulting in 430,000 new cases in 2012, and its incidence is substantially higher in men than women. Urothelial cell carcinoma, also known as transitional cell carcinoma, is the predominant histopathologic type. Bladder cancer occupies an important place in occupational epidemiology, in which associations with occupations exposed to aromatic amines were first identified in the 1950s. It is also among the first cancers for which an infectious etiology was identified, through parasitic infection with Schistosoma haematobium, which occurs in Africa and the eastern Mediterranean. Smokers have a two- to threefold increased risk of bladder cancer, and a fivefold higher risk for heavy smokers. Specific medical conditions, including urinary stones and diabetes, are positively associated with risk. Finally, bladder cancer is one of the few examples with consistent evidence of interactions between environmental exposures and genetic polymorphisms in cancer epidemiology.

In his chapter “Accomplishments in Cancer Epidemiology,” Dr. MacMahon summarizes the history of the discipline, particularly the epidemiologic evidence on cigarette smoking, ionizing radiation, occupation, the physical and microbiologic environments, the reproductive experience of women, alcohol, and iatrogenic exposures as their bear on cancer risk in humans. Ionizing radiation as a cause of leukemia and cancer of the skin, breast, lung, and thyroid is discussed in detail, as well as liver cancer and myelogenous leukemia following exposure to the X-ray contrast medium thorotrast. Important occupational carcinogens include arsenic (lung cancer, bladder cancer), asbestos (lung cancer and mesothelioma), benzene (acute myeloid leukemia), chemical dyes (bladder cancer), chromium (lung cancer), nickel (nasal cancer), and vinyl chloride (angiosarcoma in the liver). The chapter ends with a broader overview of the other environmental causes of cancers that are reviewed in detail in the site-specific chapters.

This chapter addresses the various methods for measuring cancer burden and the complexities resulting from practical applications of these measurements. It also provides an overview of global cancer patterns and trends. Epidemiological observations indicate that cancer development and progression is due to an interaction of environmental exposures with genetic factors. This underscores the importance of using complementary epidemiological measurements to obtain a cohesive and comprehensive panorama of cancer burden. Manifold measurements that capture the number of deaths, incidence/mortality rates, and time trends with respect to variations between countries, regions, and risk factors must be considered. Efforts to quantify the impact of cancer are limited primarily by the fact that only a small proportion of the global population is covered by cancer registries. Collectively, neoplasms are the second largest cause of death worldwide and deaths from site-specific cancers ascended the causes of death list in both low- and high-income countries.

Modern molecular methods are rapidly becoming an integral part of many epidemiological studies. IThile approaches to evaluate genetic factors were described in another chapter, this one deals with the use of molecular methods to measure exposure, early evidence of malignant transformation, and individual susceptibility. As we will see, such epidemiologic studies are subject to problems of design and analysis similar to those encountered in more traditional epidemiologic investigations. The use of biological measurements to assess variables of interest in epidemiological studies is not new. In the areas of infectious and cardiovascular diseases, research that would nowadays be viewed in the context of biomarkers has been conducted for decades. As an example, Figure 5-1 shows the results linking elevated serum cholesterol levels to the risk of ischaemic heart disease in the Framingham prospective study (Truett et al, 1967). During the last decade, however, the use of biomarkers in cancer epidemiology has greaily increased. Several reasons may explain this expansion. The search for carcinogens, characterrzed by complex exposure circumstances and possibly weak effects, has become increasingly difficult with traditional epidemiological approaches. An example is the investigation of the role of diet, in particular early in life, in breast carcinogenesis (Okasha et al, 2A$).In parallel, increasing knowledge of mechanisms of carcinogenesis led to the proposal of models involving genetic and epigenetic events, as well as cellular and histological alterations. These models, which need to be tested in human studies, represent a theoretical framework for molecular epidemiological research. Furthermore, developments in molecular biology and genetics, such as the use of robots and the increasing throughput of automatic analytical equipments, allow the large-scale application of assays that would otherwise be very resource intensive. It is useful to consider biomarkers in general and molecular epidemiology tools in particular within the larger framework of epidemiological studies. Epidemiology aims

This is a post-peer-review, pre-copyedit version of an article published in Cancer Causes and Control. The final authenticated version is available online at: http://doi.org/10.1007/s10552-017-0926-7. Purpose: Sun exposure is associated with risk of several chronic diseases including cancer. The study aim is to investigate whether sun behaviours are related to other lifestyle risk factors of cancer. Methods: We analysed data collected in 2003-2004 by self-completed questionnaire from 34,402 Swedish women aged 40-61 years, who comprised 70% of a cohort of originally recruited from a population registry in 1991-1992 (n=49,259). Participants were asked about annual number of sunburns and annual number of weeks of swimming and sunbathing during 1991-2002, solarium use during 1991-1998 and current sunscreen use. Results: Compared to non-drinkers, the prevalence ratio (95% CI) in women who drank >10 g of alcohol per day was 1.64 (1.49, 1.81) for having >1 sunburn per year, 1.39 (1.29, 1.51) for swimming and sunbathing >2.5 weeks per year and 1.55 (1.41, 1.70) for using a solarium >1 time per 2 months, adjusting for demographic and lifestyle variables. Tobacco smokers were less likely to report sunburn and to use sunscreen, and more likely to sunbath and use solaria, compared with non-smokers. Physical activity was associated positively with swimming and sunbathing, and with the separate use of solaria and sunscreens, but not with number of sunburns. The lifestyle variables that explained most of the variation in sun behaviour were alcohol and smoking. Conclusions: Our results suggest that alcohol consumption and tobacco smoking are potential lifestyle confounders which should be adjusted in studies investigating the association that sun and/or solarium exposure may have with risk of several cancer sites.

We evaluated the risk of bladder cancer in a cohort of 79 280 Swedish men hospitalised for benign prostatic hyperplasia (BPH), identified in the Swedish Inpatient Register between 1964 and 1983 and followed until 1989 via multiple record linkages with nationwide data on cancer registry, death and emigration. Standardised incidence ratios (SIRs), the ratios of the observed to the expected numbers of incident bladder cancers, were used to calculate the risk associated with BPH. The expected number was calculated by multiplying the number of person-years by the age-specific cancer incidence rates in Sweden for each 5-year age group and calendar year of observation. Analyses were stratified by BPH treatment, latency, calendar year and presence of genitourinary (GU) comorbid conditions. After excluding the first 3 years of follow-up after the index hospitalisation, we observed 506 incident bladder cancer cases during follow-up in the cohort. No overall increased risk of bladder cancer was apparent in our main analysis involving the entire BPH cohort. However, among BPH patients with transurethral resection of the prostate (TURP), there was an increased risk in all follow-up periods; SIRs of bladder cancer during years 4–6 of follow-up was 1.22 (95% confidence interval=1.02–1.46), 1.32 for 7–9 years of follow-up, and 1.47 for 10–26 years of follow-up. SIRs of bladder cancer among TURP-treated BPH patients were particularly elevated among those with comorbid conditions of the GU tract (e.g., stone, infection, etc.); 1.72, 1.74 and 2.01 for 4–6, 7–9, 10–26 years of follow-up, respectively, and also for those whose diagnoses occurred before 1975, when TURP was more likely to be performed by a urologist than a general practitioner: 1.87, 1.90 and 1.74, respectively. These findings suggest that BPH overall is not associated with bladder cancer risk. However, among men treated with TURP, particularly those with other comorbid GU tract conditions, risk of bladder cancer was elevated.

COX-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Accumulating evidence from epidemiologic studies, chemical carcinogen-induced rodent models and clinical trials indicate that COX-2 plays a role in human carcinogenesis and is overexpressed in prostate cancer tissue. We examined whether sequence variants in the COX-2 gene are associated with prostate cancer risk. We analyzed a large population-based case–control study, cancer prostate in Sweden (CAPS) consisting of 1,378 cases and 782 controls. We evaluated 16 single nucleotide polymorphisms (SNPs) spanning the entire COX-2 gene in 94 subjects of the control group. Five SNPs had a minor allele frequency of more than 5% in our study population and these were genotyped in all case patients and control subjects and gene-specific haplotypes were constructed. A statistically significant difference in allele frequency between cases and controls was observed for 2 of the SNPs (+3100 T/G and +8365 C/T), with an odds ratio of 0.78 (95% CI = 0.64–0.96) and 0.65 (95% CI = 0.45–0.94) respectively. In the haplotype analysis, 1 haplotype carrying the variant allele from both +3100 T/G and +8365 C/T, with a population frequency of 3%, was also significantly associated with decreased risk of prostate cancer (p = 0.036, global simulated p-value = 0.046). This study supports the hypothesis that inflammation is involved in prostate carcinogenesis and that sequence variation within the COX-2 gene influence the risk of prostate cancer. © 2006 Wiley-Liss, Inc.

Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case-control study encompassing cases with cancer of the large bowel (N=591), bladder (N=263) and kidney (N=133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300-1200 microg kg(-1)) or moderate (range 30-299 microg kg(-1)) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied.

Trends in cervical cancer incidence following the introduction of screening have mostly been studied using cross-sectional data and not analysed separately for squamous cell cancer and adenocarcinomas. Using Swedish nationwide data on incidence and mortality, we analysed trends during more than 3 decades and fitted Poisson-based age-period-cohort models, and also investigated whether screening has reduced the incidence of adenocarcinomas of the cervix. The incidence of reported cancer in situ increased rapidly during 1958–1967. Incidence rates of squamous cell cancer, fairly stable before 1968, decreased thereafter by 4–6% yearly in women aged 40–64, with a much smaller magnitude in younger and older women. An age-cohort model indicated a stable 70–75% reduction in incidence for women born 1940 and later compared with those born around 1923. The incidence of adenocarcinomas doubled during the 35-year study period. The mortality rate increased by 3.6% before 1968 and decreased by 4.0% yearly thereafter. Although a combination of organized and opportunistic screening can reduce the incidence of squamous cell cancer substantially, the incidence of adenocarcinomas appears uninfluenced by screening. © 1999 Cancer Research Campaign

To investigate the relation between diabetes mellitus and the risk of renal cell cancer we carried out a population-based retrospective cohort study. Patients identified in the Swedish Inpatient Register who were discharged from hospitals with a diagnosis of diabetes mellitus between 1965 and 1983 formed a cohort of 153 852 patients (80 005 women and 73 847 men). The cohort members were followed up to 1989 by record linkage to three nation-wide registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using age-specific sex-specific and period-specific incidence and mortality rates derived from the entire Swedish population. After exclusion of the first year of observation, a total of 267 incidences of renal cell cancer (ICD-7 : 180.0) occurred in diabetic patients compared with the 182.4 that had been expected. Increased risks were observed in both women (SIR = 1.7, 95 % confidence interval, CI = 1.4–2.0) and men (SIR = 1.3; 95 % CI = 1.1–1.6) throughout the duration of follow-up (1–25 years). A higher risk was seen for kidney cancer (ICD-7 : 180) mortality (SMR = 1.9; 95 % CI = 1.7–2.2, women; SMR 1.7, 95 % CI = 1.4–1.9, men). In comparison with the general population, patients with diabetes mellitus have an increased risk of renal cell cancer. [Diabetologia (1999) 42: 107–112]

Because Pap-smear screening can detect pre-invasive cervical cancer, such screening can markedly reduce the occurrence of invasive cancer. However, its impact in different populations is uncertain. This study compares the changes in cervical cancer incidence at different ages after the introduction of screening in different populations, and addresses the impact of organized and opportunistic smear taking. We identified 17 cancer registries large enough and existing long enough to analyze screening effects. For each registry, we calculated the relative reduction in age-specific incidence rates and in incidence rates age-standardized to the world population after the introduction of cytologic screening. In 11 of the 17 populations, age-standardized incidence rates declined markedly from 27 percent in Norway and to 77 percent in Finland. Age-specific declines were confined to women aged 30 to 70 years old with a nadir around ages 40 to 55. In six other populations, age-standardized incidence rates declined less than 25 percent, an amount too small to provide unambiguous evidence of a screening effect. In several populations, cytologic screening had a more pronounced effect than is generally recognized. Because age-specific declines in cervical cancer incidence rates were strikingly similar in populations with widely different screening practices, organized screening may not be markedly superior to opportunistic screening. The reduction in reported cancer incidence because of screening is smaller in younger and older women.

BACKGROUND: Data are scarce on the potential change in suicidal behavior among adolescents and young adults after receiving a cancer diagnosis. PATIENTS AND METHODS: We conducted a population-based cohort study including 7 860 629 Swedes at the age of ≥15 during 1987-2009. Among the cohort participants, 12 669 received a first diagnosis of primary cancer between the age of 15 and 30. We measured the relative risks (RRs) of suicidal behavior (defined as completed suicides or suicide attempts) after cancer diagnosis. We also carried out a case-crossover study nested within the cohort to adjust for unmeasured confounders. RESULTS: Twenty-two completed suicides (versus 14 expected) and 136 suicide attempts (versus 80 expected) were identified among the cancer patients. The RR of suicidal behavior was 1.6 [95% confidence interval (CI), 1.4-1.9] after a cancer diagnosis, compared with cancer-free individuals. Risk increase was greatest immediately after diagnosis; the RR was 2.5 (95% CI 1.7-3.5) during the first year after diagnosis and was 1.5 (95% CI 1.2-1.8) thereafter. This pattern was similar for completed suicide and suicide attempts. The elevated risks were evident for majority of the main cancer types, except for cancer in thyroid, testis and melanoma. The case-crossover analysis of suicidal behavior during the first year after cancer diagnosis revealed similar results. CONCLUSIONS: Adolescents and young adults receiving a cancer diagnosis are at substantially increased risk of suicidal behavior, particularly during the first year after diagnosis. Although the absolute excess risk is modest, these findings emphasize the need to support and carefully monitor this vulnerable population. Language: en

Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumours. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984, 3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germ-cell, 15 not classifiable) and 510 tumours of borderline malignant potential were diagnosed. 5 individually age-matched controls (total 19,980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95% Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.98]), and germ-cell cancer (0.71 [0.48-1.05]), but a less consistent decrease for borderline tumours (0.92 [0.81-1.04]). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94] epithelial cancer, 0.92 [0.77-1.10] stromal cancer, 0.92 [0.65-1.32] germ-cell cancer, 0.93 [0.80-1.09] borderline tumours). Because our findings cannot be readily explained by theories involving incessant ovulation or high serum concentrations of gonadotropins, new aetiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer.

Current cancer care focuses on procuring the most up-to-date therapy to prevent cancer death. However, the majority of cancer survivors will not die from cancer but from cardiovascular disease.A cancer diagnosis presents a 'teachable moment' for lifestyle behavior change.Changes in key behavioral risk factors reduce cardiovascular risk; yet, this potential for primary prevention of cardiovascular disease among cancer survivors is often overlooked.Evidence now exists for both individual clinic-based approaches and complementary community-based strategies to induce successful behavior change.We propose a systematic re-alignment of clinical and research focus to complement cancer surveillance and adjuvant treatments with key patient-and community-based strategies to improve lifestyles in cancer survivors [added].

PART I - BACKGROUND 1. Burden of Cancer 2. Origin of Cancer 3. Genetic Epidemiology of Cancer 4. Biomarkers in Cancer Epidemiology 5. Concepts in Cancer Epidemiology and Etiology PART II - CANCER EPIDEMIOLOGY BY SITE OR TYPE OF MALIGNANT TUMOR 6. Oral and Pharyngeal Cancer 7. Esophageal Cancer 8. Stomach Cancer 9. Colorectal Cancer 10. Cancer of the Liver and Biliary Tract 11. Pancreatic Cancer 12. Cancer of the Lung, Larynx, and Pluera 13. Skin Cancer 14. Breast Cancer 15. Cervical Cancer 16. Endometrial Cancer 17. Ovarian Cancer 18. Prostate Cancer 19. Testicular Cancer 20. Urinary Bladder Cancer 21. Thyroid Cancer 22. Hodgkin's Disease 23. Non-Hodgkins Lymphomas 24. Leukemias

STUDY OBJECTIVE: To ascertain, from the published reports to date, whether or not a significantly increased risk of breast cancer is specifically attributable to a history of induced abortion, independent of spontaneous abortion and age at first full term pregnancy (or first live birth); to establish the relative magnitude of such risk increase as may be found, and to ascertain and quantify such risk increases as may pertain to particular subpopulations of women exposed to induced abortion; in particular, nulliparous women and parous women exposed before compared with after the first full term pregnancy. INCLUDED STUDIES: The meta-analysis includes all 28 published reports which include specific data on induced abortion and breast cancer incidence. Since some study data are presented in more than one report, the 28 reports were determined to constitute 23 independent studies. Overall induced abortion odds ratios and odds ratios for the different subpopulations were calculated using an average weighted according to the inverse of the variance. An overall unweighted average was also computed for comparison. No quality criteria were imposed, but a narrative review of all included studies is presented for the reader's use in assessing the quality of individual studies. EXCLUDED STUDIES: All 33 published reports including data on abortion and breast cancer incidence but either pertaining only to spontaneous abortion or to abortion without specification as to whether it was induced or spontaneous. These studies are listed for the reader's information. RESULTS: The overall odds ratio (for any induced abortion exposure; n = 21 studies) was 1.3 (95% confidence interval of 1.2, 1.4). For comparison, the unweighted overall odds ratio was 1.4 (1.3,1.6). The odds ratio for nulliparous women was 1.3 (1.0,1.6), that for abortion before the first term pregnancy in parous women was 1.5 (1.2,1.8), and that for abortion after the first term pregnancy was 1.3 (1.1,1.5). CONCLUSIONS: The results support the inclusion of induced abortion among significant independent risk factors for breast cancer, regardless of parity or timing of abortion relative to the first term pregnancy. Although the increase in risk was relatively low, the high incidence of both breast cancer and induced abortion suggest a substantial impact of thousands of excess cases per year currently, and a potentially much greater impact in the next century, as the first cohort of women exposed to legal induced abortion continues to age.

The relation between obesity, particularly abdominal obesity, and risk of stroke amongst women remains unclear. In 1991–1992, a prospective study was initiated in Sweden amongst women who returned a self-administered questionnaire. Through linkage with nation-wide registries, 45 449 women, free of stroke at entry, were followed up until diagnosis of first incident stroke, death, or the end of follow-up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence intervals (CIs) from Cox proportional hazards regression models. A total of 170 incident stroke cases occurred during an average of 11 years of follow-up. The RR of stroke amongst women in the highest compared with the lowest quintile was 2.4 (95% CI 1.3–4.2; P for trend 0.04) for waist-to-hip ratio, 2.5 (95% CI 1.5–4.3; P for trend 0.01) for waist-to-height ratio and 2.3 (95% CI 1.2–4.3; P for trend 0.02) for waist circumference. Adjustment for hypertension and diabetes attenuated these risk estimates. In contrast, birth weight, body mass index (BMI) at age 18, BMI at entry, weight change in adulthood and adult height were not significantly associated with risk of stroke. This study provides evidence that, in contrast to BMI, several different measures of abdominal obesity are strong predictors of stroke in women.

α-Methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation >0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cutpoints were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cutpoint on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cutpoint developed using prostate cancer–specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.

To examine whether early anthropometric measures and reproductive factors were associated with body mass index (BMI), overweight, and obesity.Cross-sectional, observational study.In all, 18 109 healthy women who participated in the Swedish Mammography Cohort aged 49-83 y.Early anthropometric (birthweight and body shape at age 10 y) and reproductive (age at menarche, age at the birth of the first child, and parity) variables were our predictors and current BMI, overweight (BMI 25-29.99 kg/m(2)), and obesity (BMIor =30 kg/m(2)) were our outcomes.In multivariate-adjusted polytomous logistic regression analysis, risk of overweight and obesity increased with increasing body shape at age 10 y and decreased with increasing age at menarche and age at first birth (P for trend0.0001). A U-shaped relation with birthweight was observed. In our tests for effect modification of the relation with overweight/obesity (ow/ob; BMIor =25 kg/m(2)), we detected significant interactions between body shape at 10 y and age (P0.0001); body shape at 10 y and physical activity (P0.0001); age at first birth and smoking (P=0.02); and parity and physical activity (P=0.004). The increased risk of ow/ob among women who reported a larger childhood body shape was reduced as women moved from the lowest to highest quartile of physical activity in adulthood. Likewise, the increasing risk of ow/ob among women with greater parity was reduced with increased physical activity.Early anthropometric measures and reproductive factors are significantly associated with BMI, overweight, and obesity among older women. The effects of childhood body weight, age at first birth, and parity may be modified by adult lifestyle choices, as well as age.

We linked four nationwide Swedish population-based registries to identify first-degree family history of breast and ovarian cancer among breast cancer cases diagnosed between 1991 and 1998 and followed them until death, emigration or end of follow-up in December 1998. The median follow-up was 36 months. Using Cox proportional hazards models, the hazard ratio of death (HR) due to breast cancer was estimated. Women with a family history of breast or ovarian cancer (n=2175, 12.7%) had a nonsignificantly better prognosis than women without any family history, HR 0.86 (95% CI 0.71-1.05); this appeared unrelated to age at diagnosis either in the index case or in relative(s) with breast and/or ovarian cancer. Our study shows that prognostic outlook is not worse among breast cancer patients with family history.

To investigate the association between alcoholism and risk of male breast cancer.We conducted a retrospective population-based cohort study in Sweden of men diagnosed with alcoholism between 1965 and 1995. The cohort was followed up through interlinkages with nationwide registries (the national cancer registry, immigration registry, causes of death registry, and population registry), using the national registration numbers. Standardized incidence ratios (SIRs), calculated using the Swedish national cancer incidence rate as reference, were used as estimates of relative risks.A total of 145,811 men were enrolled into the cohort, contributing 1,499,504 person-years of follow-up. Sixteen incident breast cancer cases were identified, and the mean age at diagnosis was 68 years. We excluded the first year of follow-up (cases and person-years) from the analysis to avoid detection bias. The overall SIR (excluding the first year of follow-up) was 1.1 (95% CI 0.6-2.0). Although based on small numbers we found no indication of a differential SIR according to duration of follow-up, age at cohort enrolment, or age at follow-up (attained age or age at cancer diagnosis).The observed associations are not compatible with an increase in breast cancer risk among male alcoholics.

To investigate how attitudes and beliefs about Pap smear screening affect women's choice to participate in organized or opportunistic screening.Telephone interviews were conducted with 430 (69.0%) non-attenders and 514 (80.7%) attenders to Pap smear screening, sampled from a population-based database. The interviews were conducted during 1998 in Uppsala County, Sweden.odds ratios (OR) and 95% confidence intervals (CI).Non-attendance was negatively associated with perceived severity of cervical cancer compared to other malignancies (OR = 1.9, 95% CI 1.1-3.4) as well as with satisfactory benefits (OR = 0.7, 95% CI 0.6-0.8), but positively associated with time-consuming and economical barriers (OR = 1.2, 95% CI 1.1-1.5 and OR = 1.7, 95% CI 1.2-2.5, respectively). Non-attendance was also negatively associated with anxiety, but was of borderline significance (OR = 0.9, 95% CI 0.8-1.0). The results were strengthened with increasing time since last smear or if self-reported attendance status was used instead of true attendance. Non-attenders kept holding harder to their preferences than did attenders, stating they would not participate if their preferences were not met.Important differences in attitudes and beliefs exist between non-attenders and attenders in Pap smear screening. Rather than being emotional, the main barriers are either practical or rooted in misunderstandings and lack of relevant information. These insights offer opportunities to increase attendance rates considerably.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMIor = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

Linkage of nationwide databases in Sweden allowed us to evaluate the incidence of ovarian cancer among 36,856 women diagnosed with alcoholism between 1965 and 1994. Mean duration of follow-up was 9.6 years, for a total of 317,518 person-years at risk. The expected number of cases of ovarian cancer was calculated by multiplying the number of person-years by 5-year age group and calendar year-specific incidence rates of ovarian cancer in Sweden. The effect measure was the standardized incidence ratio (SIR), with 95% confidence intervals (CIs). Our results indicate an overall deficit of cases of ovarian cancer of about 14% among women with a diagnosis of alcoholism. This deficit is particularly strong and statistically significant among alcoholic women younger than 60 years (SIR = 0.76, 95% CI 0.58-1.00). This deficit is compatible with the reported reduction of gonadotrophin levels among alcoholic women younger than 60 years and with the hypothesis invoking these gonadotrophins in the etiology of ovarian cancer.

To examine the hypothesis that sedentary women have an increased risk of endometrial cancer compared to physically active women.This is a population-based case-control study in the entire Swedish female population aged 50-74 years in 1994-1995. We obtained self-reported information on leisure-time physical activity during childhood, at ages 18-30, and recently from 709 incident case women with endometrial cancer and 3368 population controls. Occupational physical activity was estimated through record linkage to the Swedish census data from 1960, 1970, 1980, and 1990. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for different activity levels by multivariate logistic regression, taking into account potential confounders.Comparing lowest to highest (reference) levels of physical exercise, we observed statistically significant associations with risk of endometrial cancer for leisure-time activity at age 18-30 years (multivariate OR = 1.4; 95% CI = 1.0-1.8; p for trend 0.01) and in recent years (multivariate OR = 1.3; 95% CI = 1.0-1.7; p for trend 0.01). We found similar associations comparing lowest to highest (reference) levels of occupational activity assessed at the censuses in 1980 (multivariate OR = 1.4; 95% CI = 1.0-1.9; p for trend 0.03) and 1990 (multivariate OR = 1.3; 95% CI = 0.9-1.9, p for trend 0.05), but a less consistent association with censuses in 1960 and 1970. The increased risk associated with low level of occupational physical activity was confined to women who were not obese and to women who were smokers.Our data, in conjunction with past epidemiological studies, indicate that both occupational and leisure-time physical activity may reduce the risk for postmenopausal endometrial cancer.

A population-based cohort study of 36 856 women diagnosed with alcoholism in Sweden between 1965 and 1995 found that alcoholic women had only a small 15% increase in breast-cancer incidence compared to the general female population. It is therefore apparent, contrary to expectation, that alcoholism does not increase breast-cancer risk in proportion to presumed ethanol intake. © 2000 Cancer Research Campaign

Insulin-like growth factor 1 (IGF-1) is a potentially important determinant of disease; hence epidemiological identification of factors that influence circulating IGF-1 is merited. We therefore analysed data collected in Greece to determine the relationship between anthropometric, lifestyle and dietary variables and serum levels of IGF-1 among elderly men. We identified 51 men with prostate cancer, 50 men with benign prostatic hyperplasia, and 52 apparently healthy elderly men (controls), all matched for age (+/- 1 year). These 153 men provided blood specimens and were interviewed using a validated lifestyle and food frequency questionnaire. We performed multivariate linear regression to identify potential predictors of circulating IGF-1. After controlling for age, body mass index, smoking habits, alcohol drinking and coffee consumption, each 5 cm increase in height predicted a 13.0% increase in IGF-1 (95% CI 0.4-27.2%) among the controls and a 11.3% increase in IGF-1 (95% CI 4.5-18.6%) among the entire study group. None of the investigated dietary factors (total fat, carbohydrate, protein, dairy products, tomatoes, calcium) were strongly related to IGF-1 levels. The positive association between IGF-1 and height integrates the empirical evidence linking IGF-1 and height with prostate cancer risk.

To clarify whether type and timing of physical activity affect postmenopausal breast cancer risk.In a population-based case-control study within the Swedish female population 50-74 years of age, 3347 women with invasive, postmenopausal breast cancer (84% of all eligible) and 3455 controls (82% of all selected) reported on past leisure-time physical activity. Record linkage to decennial census data (1960-1990) provided estimates of their occupational physical activity. Odds ratios with 95% confidence intervals were estimated by multivariate logistic regression.After adjustment for potential confounders, women in sedentary occupations during their reproductive years (25-44 years of age) had a 50% higher risk for postmenopausal breast cancer, compared to those with the physically most demanding jobs. Only the most recent leisure-time physical activity was associated with a significant risk reduction. Women with the combination of sedentary jobs and lack of leisure-time exercise had a three-fold higher risk of breast cancer, compared to the physically most active both inside and outside the workplace.Effects of occupational and leisure-time physical activity on breast cancer risk appear to have different latency times, and/or to be effect-modified by age or reproductive status. Although chance might explain our findings, it is advisable to consider type and timing of physical activity in future studies.

To measure the association between endometrial cancer risk and obesity at age 18 and recently, adult weight gain, diabetes mellitus and hypertension.We performed a population-based, nationwide case-control study among postmenopausal women aged 50-74 years in Sweden, including 709 incident cases with histopathologically verified endometrial cancer and 3368 controls.Compared to lean women (recent body mass index (BMI), i.e. kg/m2 below 22.5), overweight women (recent BMI 28-29.99) had a 50% increase in risk for endometrial cancer (OR 1.5, 95% CI 1.0-2.1). Obese women (recent BMI 30-33.99) had a 3-fold increased risk (OR 2.9, 95% CI 2.0-4.0), and markedly obese women (recent BMIor = 34) a 6-fold increased risk (OR 6.3, 95% CI 4.2-9.5). The OR for Type 2 diabetes mellitus was 1.5 (95% CI 1.0-2.1) and for Type 1 diabetes mellitus it was 13.3 (3.1-56.4). The effect of recent BMI was similar for tumors having different degrees of differentiation and myometrial invasion, and did not vary with age, time since menopause, smoking status, diabetes mellitus, and use of contraceptives. Hypertension increased risk only among obese women. BMI at age 18, height, and adult weight change were not independent risk factors.Recent overweight/obesity and diabetes mellitus (Types 1 and 2) are associated with endometrial cancer risk. Hypertension increases risk among obese women.

This large population-based nested case-control study investigated the importance of perinatal characteristics as risk factors for prostate cancer in later life in a cohort of men who were born between 1889 and 1941 in Stockholm, Sweden. Eight hundred and thirty-four prostate cancer cases over 18 years of age and of singleton birth were identified from the cohort between 1958 and 1994. For each case, singleton males born live to the first four mothers admitted after the case's mother were selected as potential controls; 1880 eligible controls were included in the study. For each study subject, we obtained data on mother's parity, pre-eclampsia or eclampsia before delivery, age at delivery, and socioeconomic status, as well as child's birth length and weight, placental weight, and gestational age. Odds ratio (OR) estimates and 95% confidence intervals (CIs) were derived from logistic regression analyses. We found no statistically significant differences between cases and controls with respect to maternal age, socioeconomic status, or parity. Birth weight, birth length, and placental weight were also not significantly related to prostate cancer risk. Pregnancy toxemia (OR = 0.33; 95% CI, 0.07-1.45) and longer gestation age were associated with a reduced risk of prostate cancer; the OR estimate was 0.94 (95% CI, 0.89-0.99) for each 1-week prolongation of the duration of gestation. Our results suggest that birth size indicators are not important risk factors for prostate cancer in later life. In addition, our data on gestation age indicate that the late in utero environment may be as important as the early in utero environment in the modulation of prostate cancer risk in offspring.

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [/= 2 packs per day, odds ratio (OR)=2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.

The causes of renal cell cancer remain incompletely understood. In one previous retrospective case-control study, high occupational physical activity has been associated with a decreased risk among men, but not among women. Our aim was to investigate the association between occupational physical activity and renal cell cancer in a large cohort in Sweden. A cohort of Swedish men and women was identified in the nationwide censuses in 1960 and 1970, and the reported occupations were classified into 4 levels of physical demands. Follow-up from 1971 through 1989 was accomplished through record linkages to the Swedish Cancer Registry. Multivariate Poisson regression models were used to estimate relative risk (RR) and 95% confidence intervals (CI). We found a monotonic increase in risk of renal cell cancer with decreasing level of occupational physical activity among men (p for trend0.001). After adjustment for socio-economic status, place of residence, and calendar year of follow-up, men with long-term sedentary jobs had a 25% (RR = 1.25, 95% CI 1.02-1.53) increased risk compared to men with physically demanding occupations. Among women there was no association, the dose-risk trend was not significant (p for trend0.50). Occupational physical activity was inversely associated with renal cell cancer among men. The absence of association among women might be due to smaller range of exposure, confounding by household work or reproductive factors, or to a difference in biological response to physical activity in men and women.

Recent data suggest that the IGF system plays an important role in the pathogenesis of several forms of human cancer, and there is evidence that IGFs acting in an autocrine and paracrine manner may also affect colorectal cancer risk. We have conducted a case-control study on the island of Crete, Greece, to examine the potential relation between circulating IGF-I and -II and their major binding protein (IGF-BP3), on the one hand, and colorectal cancer, on the other. IGF-I, IGF-II and IGF-BP3 were determined in the serum from 41 patients with colorectal cancer and 50 healthy controls; data were analyzed using unconditional multiple logistic regression, adjusting for age, gender, education, height and BMI, as well as mutually. Both IGF-I and IGF-II were positively, while IGF-BP3 was inversely, associated with risk for colorectal cancer, though none of these relations reached statistical significance. However, individuals with IGF-I and -II values in the upper 2 tertiles of the respective distributions had a significantly elevated odds ratio for colorectal cancer (OR = 5.2, 95% confidence interval 1.0-26.8) compared with those in the lower tertile in both distributions. Our results provide evidence that high levels of circulating IGF-I and -II might be associated with colorectal cancer.

BACKGROUND—The quality of rectal cancer surgery at small units has been debated. No national studies of this issue have been undertaken and most studies have been based on insufficient data to clarify the controversy. It has been claimed that observed differences in outcomes between specialised centres and smaller hospitals are confounded by differences in stage/severity. AIM—To compare survival after rectal cancer between hospital catchment areas. PATIENTS—All patients with rectal cancer notified to the Swedish Cancer Register in 1973-1992 (n = 30 811) were followed up by record linkage to the nationwide Death Register. METHODS—Relative survival—that is, ratio of observed to expected survival—was computed as a measure of excess mortality attributable to rectal cancer. Multivariate analysis was then performed to estimate the independent effects of hospital catchment area categories and age, year of diagnosis, and duration of follow up. RESULTS—One year relative survival among rectal cancer patients residing in catchment areas of large regional hospitals was 76%, compared with 72% for small local hospitals (p

An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.