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The effectiveness of Rappaport-Vassiliadis enrichment medium (RV medium) and Difco's tetrathionate brilliant green broth (TBG) for detection of Salmonella in 553 samples of meat products was compared. All samples were preenriched for 20 h in buffered peptone water. Then 0.1 ml of the preenrichment was inoculated into 10 ml of RV medium, 1 ml was added to 9 ml of TBG broth, and 1 ml was inoculated into 10 ml of Muller-Kauffman (MK) tetrathionate broth. All enrichments were incubated at 43°C for 24 h, except for MK broth which was incubated for 48 h, and all were subcultured onto brilliant green deoxycholate agar and bismuth sulfite agar. The Rappaport-Vassiliadis medium was superior to Difco's tetrathionate brilliant green broth, being considerably more sensitive and more specific. The superiority of RV medium concerned the number of positive samples (36% and 28%, respectively), and also the number of Salmonella serotypes and strains. The RV medium inhibited the lactose- and sucrose-negative competing organisms much more than the Difco's tetrathionate broth. The performance of Difco and Muller-Kauffman tetrathionate brilliant green broths was similar. Addition of the brilliant green solution after boiling the tetrathionate broth slightly increased its efficacy. The effectiveness of brilliant green deoxycholate agar and bismuth sulfite agar was similar, whether after enrichment in RV medium or in any of the studied tetrathionate brilliant green broths.

Background and aims High glycemic load (GL) has been associated with increased coronary heart disease (CHD) risk. We evaluated whether preference of low-GL foods conveys incremental benefits with respect to CHD, especially to people adhering to the traditional Mediterranean diet (MD). Methods and results We analyzed data from the Greek European Prospective Investigation into Cancer and Nutrition, including 20,275 participants free of cardiovascular diseases, cancer, or diabetes at baseline and without incident diabetes. Subjects completed a validated, semi-quantitative food frequency questionnaire at enrollment. We calculated a 10-point MD adherence score and the dietary GL, and estimated hazard ratios (HRs) for CHD incidence and mortality through Cox proportional hazard regression. After a median follow-up of 10.4 years, 417 participants developed CHD, and 162 died from the disease. A significant positive association of GL with CHD incidence emerged (HR for the highest versus the lowest tertile = 1.41, 95% confidence interval, CI: 1.05–1.90). HRs for CHD mortality exceeded unity but were not statistically significant. The association with GL was stronger among subjects with higher body mass index. High adherence to MD with low/moderate GL was associated with lower risk of CHD incidence (HR = 0.61, CI: 0.39–0.95) and mortality (HR = 0.47, 95% CI: 0.23–96). Conclusion High dietary GL increases the risk of CHD. Compared to a high GL diet with suboptimal adherence to the traditional Mediterranean pattern, a low/moderate GL diet that also conforms to the traditional MD principles could lead to a 40% reduced risk for CHD, and over 50% reduced risk for death from CHD.

Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.

Item does not contain fulltext We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07-1.41, P(trend)=0.02). After calibration to allow for measurement error, we estimated that a 35-g day(-1) increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1-72%, P(trend)=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.

Objective: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States.

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.

In studies of the health effects of exposure to environmental tobacco smoke (ETS), misclassification of active smokers has the potential to bias the estimates of disease risk. Biochemical validation of exposure to ETS can provide objective evidence of current smoking status in epidemiological studies. Intrinsic to this effort is the establishment of appropriate cut-off points for the measurements of tobacco biomarkers. Within a collaborative study on ETS co-ordinated by the International Agency for Research on Cancer, questionnaire data and urine samples were collected from 1,369 women at 13 centres in 10 countries. Forty seven of these women had urine cotinine levels above 50 ng.mg-1 creatinine, a level used to discriminate smokers from nonsmokers in previous studies. The distributions of the subjects across cotinine values and self-reported exposure to ETS was consistent with the association, at one extreme, of moderate cotinine levels (50-150 ng.mg-1) with very high exposure to ETS, and, at the other extreme, of very high cotinine levels indicating actual use of nicotine-containing products in women with low ETS exposure. Using the cut-off point of 150 ng.mg-1, only 1.5% of the alleged nonsmokers were reclassified as current light smokers. Potential bias due to smoker misclassification is very unlikely to be responsible for the increased health risks observed in epidemiological studies on ETS.

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.

Udgivelsesdato: 2010-Jan-28 Abstract. Bamia C, Halkjaer J, Lagiou P, Trichopoulos D, Tjønneland A, Berentzen TL, Overvad K, Clavel-Chapelon F, Boutron-Ruault M-C, Rohrmann S, Linseisen J, Steffen A, Boeing H, May AM, Peeters PH, Bas Bueno-de-Mesquita H, van den Berg SW, Dorronsoro M, Barricarte A, Rodriguez Suarez L, Navarro C, González CA, Boffetta P, Pala V, Hallmans G, Trichopoulou A (University of Athens, Athens, Greece; Institute of Cancer Epidemiology, Copenhagen, Denmark; Harvard School of Public Health, Boston, MA, USA; Bureau of Epidemiologic Research, Athens, Greece; Hellenic Health Foundation, Athens, Greece; Institute of Preventive Medicine, Copenhagen, Denmark; Institute of Public Health, Aarhus University, Aarhus, Denmark; Center for Cardiovascular Research, Aalborg, Denmark; Institut Gustave-Roussy, Paris, France; German Cancer Research Centre, Heidelberg, Germany; Institute of Epidemiology, Potsdam, Germany; German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany; University Medical Center Utrecht, Utrecht, the Netherlands; Public Health and Primary Care, London, UK; National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Public Health Department of Gipuzkoa & Ciberesp, San Sebastian, Spain; Health Institute of Navarra, Pamplona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Health and Healthcare services council, Asturias, Spain; Murcia Regional Health Council, Murcia, Spain; Catalan Institute of Oncology, Barcelona, Spain; International Agency for Research on Cancer, Lyon, France; Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy; and Nutritional Research, Umea, Sweden). Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition-Elderly Network on Ageing and Health study. J Intern Med 2010; 000: 000-000. Objective. Later life weight change and mortality amongst elders. Design. Nested case-control study. Setting. Six countries from the European Investigation into Cancer and nutrition - Elderly, Network on Ageing and Health. Subjects. A total of 1712 deceased (cases) and 4942 alive (controls) were selected from 34 239 participants, >/= 60 years at enrolment (1992-2000) who were followed-up until March 2007. Annual weight change was estimated as the weight difference from recruitment to the most distant from-date-of-death re-assessment, divided by the respective time. Outcome measures. Mortality in relation to weight change was examined using conditional logistic regression. Results. Weight loss >1 kg year(-1) was associated with statistically significant increased death risk (OR = 1.65; 95% CI: 1.41-1.92) compared to minimal weight change (+/-1 kg year(-1)). Weight gain >1 kg year(-1) was also associated with increased risk of death (OR = 1.15; 95% CI: 0.98-1.37), but this was evident and statistically significant only amongst overweight/obese (OR = 1.55; 95% CI: 1.17-2.05). In analyses by time interval since weight re-assessment, the association of mortality with weight loss was stronger for the interval proximal (

The phagocytic activity of mononuclear phagocytes of A/J mice and Wistar rats was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. In mice, the overall phagocytic activity was significantly increased at the end of the first week (P less than 0.0001), but the increase was marginal by the third and fourth weeks after injection. A significant increase in the relative weight of liver and spleen was observed even when phagocytic activity had returned to levels similar to those of controls (P less than 0.001). In rats, the overall phagocytic activity was significantly increased until the fourth week (P less than 0.00001). There was not, however, an increase in the relative weight of liver and spleen as observed for the mice. The results are discussed in the context of factors contributing to the pathogenic mechanisms responsible for differences in the patterns of arthritis due to mycoplasma observed in mice and rats.

Background: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer. Methods: We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. This study includes 630 incident prostate cancer cases and 630 matched control subjects. Odds ratios and their 95% confidence intervals (95% CI) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression. Results: The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 (95% CI, 0.99-1.82; Ptrend = 0.08) for IGF-I, 1.39 (95% CI, 1.02-1.89; Ptrend = 0.12) for the IGF-I residuals after adjusting for IGFBP-3, 1.22 (95% CI, 0.92-1.64; Ptrend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74-1.37; Ptrend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease, although the association of serum IGF-I concentration with risk was slightly stronger for advanced-stage disease; the odds ratio for the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; Ptrend = 0.21) for IGF-I and 1.76 (95% CI, 0.92-3.40; Ptrend = 0.11) for IGF-I adjusted for IGFBP-3. Conclusions: In this large nested case-control study, serum IGF-I concentration is not strongly associated with prostate cancer risk, although the results are compatible with a small increase in risk, particularly for advanced-stage disease; no association for IGFBP-3 was observed. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1121–7)

To be fit as we age could be described as "Age fitness". Increasing evidence points to opportunities for greater wellness, health maintenance and reduction of the burden of disease in later life for a growing proportion of the community than previously envisaged. The scope of "age fitness" is social, mental, physiological and physical. We know a great deal about food cultures associated with successful aging--Greek, Okinawan, and Scandinavian, for example. Within these cultures, we are beginning to account for variances in health and survival by integrative scores of food intake and their validation.

OBJECTIVE: To investigate the effects of variable amounts of tobacco smoking on body mass index and waist-to-hip ratio among current smokers. DESIGN: Population-based cohort study. SUBJECTS: A total of 22 059 apparently healthy men and women, who enrolled in the Greek EPIC cohort, aged 25-84 years, who had never smoked (14 751) or were current cigarette smokers (7308). MEASUREMENTS: Body mass index and waist-to-hip ratio (by anthropomentry), amount of tobacco smoking and energy expenditure (by an interviewer-administered, lifestyle questionnaire), energy intake and ethanol intake (by an interviewer- administered, validated, semiquantitative, food frequency questionnaire), at enrollment. RESULTS: In comparison to nonsmokers, smokers of the average number of cigarettes have lower body mass index. Among smokers, however, increased amount of smoking tends to be positively associated with body mass index, particularly among men. Waist-to-hip ratio is positively associated with amount of cigarettes smoked per day, among both men and women. CONCLUSION: Among smokers, tobacco smoking is positively associated with body mass index and waist-to-hip ratio. Our data suggest that the lower body mass index of smokers compared to nonsmokers reflects personality characteristics of those who choose to smoke and that the tendency to gain weight after smoking cessation may have behavioral rather than tobacco-related pharmacological roots.

We have assessed the ability of the Emergency Department Injury Surveillance System (EDISS), a registration network operating with limited resources, to predict the burden and pattern of injuries in the whole Greece.We have compared hospitalizations calculated on the basis of EDISS with those routinely recorded by the National Statistical Service countrywide. EDISS relies on data collected in the Emergency Departments of four hospitals, two located in the Greater Athens area, and two district hospitals in the remaining Greece. EDISS data concern hospitalized and non-hospitalized patients of all ages, with all types of injuries irrespectively of their etiology or intent.Over a three-year period 148 835 subjects with injuries were interviewed. Using sampling ratios of 2.2% for all injuries outside Greater Athens and for adults in Greater Athens but 28.9% for childhood injuries, the total annual number of injuries in Greece was estimated at 1.53 million (95% confidence interval: 1.48-1.57 million). Of those, about 18% concern children less than 15 years old. The difference between the EDISS estimated and the actually recorded hospitalized injuries was, in preliminary terms, acceptable.Of the ten major categories of injuries, seven among children and five among adults have shown deviations of less than 20%. For the remaining categories deviations were larger but in only one instance did the difference exceed 50%. It is concluded, that for a small and relatively homogeneous country, like Greece, injury data provided by four large hospitals can generate reasonably reliable estimates for large categories of injuries.

Since sports participation entails the risk of injuries that account for substantial morbidity and disability, the existence of adequate epidemiological information is essential for the development of sound preventive strategies. In this study, we present data on the occurrence of sports injuries among children in six European countries, namely Austria, Denmark, France, Greece, The Netherlands, and the United Kingdom. An operational definition for sports injuries was developed, and comparable data from the European Home and Leisure Accident Surveillance System, an established injury surveillance system operating in 12 European union countries, were collected from the participating member states, during a 1-year period (1998). Sports injuries were examined in schools, in organised and unorganised settings, and in specific types of sports by demographics and injury descriptive variables. Sports injuries represent a quantitatively important and sufficiently serious problem in European union countries, accounting for an estimated annual number of about a quarter of a million outpatient visits in two of the participating countries, which provide national estimates. It is evident, that sport injuries are not only common but also injuries of considerable severity, since a large fraction represents fractures, while approximately 4% of the total require hospitalisation. Football and basketball among male children are, in declining order, the two sports responsible for the most frequent injuries in the European union countries, whereas gymnastics and volleyball prevail among females. The study indicates the importance of injury surveillance in describing the epidemiology of sports injuries and provides an estimate of the magnitude and the profile of sport injuries that take place annually in European union countries.

The aim of this case-control study was to identify and quantify risk factors of injuries in playgrounds, where children spend an increasing amount of time in developed countries. The study took place in Greater Athens during 1999. A continuous Emergency Departments Injury Surveillance System (EDISS) of hospitals that cover about 30% of the children's time at risk in Greater Athens identified 777 injuries in public and private playgrounds out of a total of 17 497 injuries. Public playgrounds differ from private ones, because the former generally have more equipment, usually of greater height, with less resilient surfaces, and supervision relies mainly on parents or guardians. Patterns of type of playground use were assessed in a sample of 294 children from the same study base who served as a control group in a hierarchical case-control design. The annual incidence of playground injuries in Greater Athens was about 7 in 1000 among boys and 4 in 1000 among girls, with a 2.2 times higher risk for an injury in public than in private playgrounds (95% confidence interval 1.61-3.07). Children in public vs private playgrounds had a statistically significant eight times higher odds for concussion and six times higher for open wounds, whereas the odds for long bone fractures were four and for other fractures two; swings, slides and seesaws were the types of equipment most frequently associated with injuries. It was further shown that supervision of children was suboptimal (60%) in both public and private playgrounds, and children in private playgrounds sustained an unduly high frequency of sprain/ dislocation injuries (odds ratio 1.75) because they were encouraged to play bare-footed.Close to 50% of playground injuries could be prevented by structural and equipment changes, while further reduction could be accomplished through simple measures including closer supervision and encouraging children to wear proper shoes and use protective equipment whenever necessary.

Injuries related to central heating devices represent a non-negligible fraction of all indoor injuries among children with mechanical lesions, outnumbering burns. Prevention strategies refer mainly to modifications or safer use of the appliances and improvements in building design.

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.

Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL.The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers.There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19.Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.

To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted.IGF-1 declined significantly by almost 25% among men aged75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day.The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.

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.

Policies and measures for the prevention of human immunodeficiency virus Type 1 (HIV-1) transmission require adequate information about the risk profile of AIDS which is time-, place- and population-dependent. We have studied the risk factors for AIDS among men in Greece, a country with relatively low incidence of AIDS.A case-control study of all male patients with incident disease, who have been diagnosed in the major university-affiliated, AIDS Unit from February 1995 through August 1997 was conducted in Athens, Greece, a country with relatively low incidence of AIDS. Eighty-three AIDS patients were enrolled and an equal number of orthopaedic patients as controls. All interviews were conducted by the same physician and took place in the hospital.There were no differences among heterosexual men with AIDS, homo- or bi-sexual men with AIDS, and controls with respect to any socio-economic variable. The odds ratio for AIDS among homo- or bi-sexual men, in comparison with heterosexual men, was 51.5 (95% confidence intervals 21.6-122.7). Blood transfusion, intravenous drug abuse and haemophilia were less important risk factors for AIDS in this study. Condom use was generally very low and there was a tendency for lesser use among men at highest risk for HIV transmission, that is, those with a preference for receptive anal intercourse.AIDS among men in Greece is mainly driven by homosexual behaviour, but the relatively high proportion of bisexual men and the relatively low frequency of condom use are warning signs for the potential of the epidemic to expand in the future. The relatively low incidence of AIDS in Greece, in comparison with other European populations, may be due to a phase difference in the epidemic, but it could also be due to the traditional role separation of homosexuals in this geographical area, and the easy accessibility of disposable syringes and needles in Greece.

The incidence of cancer overall in Mediterranean countries is lower than in Scandinavian countries, the United Kingdom, and the United States. This is mostly accounted for by the lower incidence among Mediterranean countries of cancer of the large bowel, breast, endometrium, and prostate. These forms of cancer have been linked to dietary factors, particularly low consumption of vegetables and fruit, and to a certain extent, high consumption of meat. The traditional Mediterranean diet is characterized by high consumption of foods of plant origin, relatively low consumption of red meat, and high consumption of olive oil, which in several studies has been reported to be more beneficial against cancer than other forms of added lipids. By taking into account the established or presumed nutritional causation of major forms of cancer and the composition of the traditional Mediterranean diet, estimates can be derived concerning the fraction of cancer occurrence in highly developed Western countries that could be attributed to their diets in comparison with the healthy traditional Mediterranean diet. Although estimates can only be crude, it can be calculated that up to 25% of the incidence of colorectal cancer, approximately 15% of the incidence of breast cancer, and approximately 10% of the incidence of prostate, pancreas, and endometrial cancer could be prevented if the populations of highly developed Western countries could shift to the traditional healthy Mediterranean diet.

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.

Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States.We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data.The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer.The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer.Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base.There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer.We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.

The insulin-like growth factor (IGF) axis has important autocrine, paracrine, and endocrine roles in the promotion of growth. Alterations of the IGF system have recently been implicated in the pathogenesis of several malignancies, but the relation to hepatocellular carcinoma (HCC) risk is unclear. To address this issue, we used an immunoradiometric assay to quantify IGF-1 levels in serum samples in a hospital-based, case-control study in Greece. The study subjects were all men and included 53 patients with HCC positive for hepatitis B and/or hepatitis C virus infections, 20 virus-negative HCC patients, 25 virus-negative patients with metastatic liver cancer (MLC), and 111 virus-negative control subjects. Data were analyzed by multiple linear regression, using IGF-1 as the dependent variable. The mean value of IGF-1 was 65.9 ng/ml among virus-positive HCC patients, 79.5 ng/ml among virus-negative HCC patients, 110.8 ng/ml among patients with MLC, and 174.7 ng/ml among hospital controls. After controlling for the degree of liver damage, as assessed by prothrombin time and serum albumin level, the reduction in IGF-1 level among HCC patients was found to be more than could be attributed to liver damage alone. This finding may have both diagnostic and pathophysiological implications.

The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC).During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays.The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5-78.3) for the presence of HBsAg and 23.2 (11.4-47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9-216.6) compared to infection with neither virus.Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.

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.

To better understand the nutritional etiology of squamous cell esophageal cancer, we conducted a case-control study in 3 areas of northern Italy. A total of 304 incident, histologically confirmed cases of squamous cell carcinoma of the esophagus (275 men, 29 women) and 743 hospital controls (593 men, 150 women) with acute, non-neoplastic conditions, not related to smoking, alcohol consumption or long-term diet modification, were interviewed during 1992 to 1997, The validated food-frequency questionnaire included 78 questions on food items or recipes, which were then categorized into 19 main food groups, and 10 questions on fat intake pattern. After allowance for age, sex, education, area of residence, tobacco smoking, alcohol drinking and non-alcohol energy, a significant increased risk emerged for high consumption of soups (OR=2.1 for the highest vs. lowest quintile), whereas inverse associations with esophageal cancer risk were observed for pasta and rice (OR=0.7), poultry (OR=0.4), raw vegetables (OR=0.3), citrus fruit (OR=0.4) and other fruit (OR=0.5). The associations with dietary habits were consistent in different strata of tobacco smoking and alcohol drinking. Among added lipids, olive oil intake showed a significant reduction of esophageal cancer risk, even after allowance for total vegetable consumption (OR=0.4), while butter consumption was directly associated with this risk (OR=2.2). Our results thus provide further support to the evidence that raw vegetables and citrus fruit are inversely related to the risk of squamous cell esophageal cancer and suggest that olive oil may also reduce this risk. Int. J. Cancer 87:289-294, 2000. (C) 2000 Wiley-Liss, Inc.

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.

Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change.The data derive from a population-based case-control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n = 2015) were identified through state tumor registries and controls (n = 2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women.We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P = 0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger).Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.

A high total number of full-term pregnancies is associated with a reduced risk of breast cancer, though pregnancy transiently increases the risk of the disease. However, little attention has been given to a possible association of breast cancer risk with the gender of offspring, even though male fetuses have been associated with several factors linked to a low breast cancer risk, namely, pregnancy toxemia, increased levels of alpha-fetoprotein (AFP) and increased levels of sex hormone-binding globulin. We used data from linked Swedish registries to study the relative importance of male and female offspring as risk correlates of subsequent breast cancer in the mothers. In a nested case-control study, case patients were 2,328 women who had one or more live-born children delivered between 1973 and 1989 and who were subsequently diagnosed with breast cancer during this period. For comparison, 10,256 control subjects, matched to cases by birth year, were randomly selected from among the eligible women. Number of boys was inversely associated and number of girls positively associated with breast cancer risk. Neither of these trends was significantly different from the null value, but the difference between the 2 trends was marginally significant (p=0.06). Moreover, women who gave birth to 2 or more boys but no girls were at significantly lower risk for breast cancer in comparison to women who gave birth to 2 or more girls but no boys; the odds ratio was 0.78 (95% CI 0.64-0.95). The apparently protective effect of pregnancies with male fetuses was limited to women younger than 40 years. Endocrine or other metabolic processes specifically associated with a male rather than a female fetus may impart relative protection against the occurrence of breast cancer during the childbearing period.

A case-control study of prostate cancer (PC) was undertaken in Athens, Greece. Cases were 320 patients with histologically confirmed incident disease, whereas controls were 246 patients without history or symptomatology of benign prostatic hyperplasia, treated in the same hospitals as the cases for minor diseases or conditions. Cases and controls had similar distributions with respect to height, body mass index, sibship size and birth order in the parental family, marital status and number of offspring in the subject's own family and a long series of previous surgical operations and medical diagnoses, including diabetes mellitus, hepatitis and sexually transmitted diseases. There was also no evidence for a positive association between vertex baldness, tobacco smoking and drinking of coffee or alcoholic beverages, on the one hand, and PC, on the other. There was evidence, however, that some aspect of urban life may increase the risk for PC and a suggestion that sexual activity in early adulthood may be inversely associated with this risk.

The nutritional aetiology of prostate cancer was evaluated in Athens, Greece, through a case-control study that included 320 patients with histologically confirmed incident prostate cancer and 246 controls without history or symptomatology of benign prostatic hyperplasia or prostate cancer, treated in the same hospital as the cases for minor diseases or conditions. Among major food groups, milk and dairy products as well as added lipids were marginally positively associated with risk for prostate cancer. Among added lipids, seed oils were significantly and butter and margarine non-significantly positively associated with prostate cancer risk, whereas olive oil was unrelated to this risk. Cooked tomatoes and to a lesser extent raw tomatoes were inversely associated with the risk for prostate cancer. In analyses focusing on nutrients, rather than foods, polyunsaturated fats were positively and vitamin E inversely associated with prostate cancer. We conclude that several nutrition-related processes jointly contribute to prostate carcinogenesis.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.

Mortality from childhood cancer in general and childhood leukemia in particular has sharply declined in economically developed countries over the last 30 years, whereas the incidence of these diseases has remained essentially unaltered. Therefore, childhood malignancies can be used as tracers of accessibility to and effectiveness of medical care. The objective of this study was to compare the reduction of mortality from childhood cancer in general, and childhood leukemia in particular, in four economically developed areas of the world, to assess accessibility to and effectiveness of technologically advanced medical care.The authors used data from the World Health Organization to compare the evolution over time of gender specific, age-adjusted mortality from childhood cancer in general and childhood leukemia in particular in the childhood (birth to age 14 years) populations of North America, western Europe, Japan, and Australia and New Zealand during the period 1960-1993. They assessed the evolution over time and the cumulative percentage representing the decline in mortality from childhood cancer and childhood leukemia in the four aforementioned areas of the world.The decline in mortality from both the disease entities considered and for both genders has been more pronounced in North America than in other economically developed areas of the world.When disease control depends on technologically advanced medical care, as in the case of cancer, the North American population is benefited by earlier and effective introduction of new therapeutic approaches. This conclusion does not apply to other childhood diseases, the incidence of which is higher among low-income groups and control of which depends on prevention rather than treatment.

This study examines the relationship between a series of epidemiologic parameters (age, height, body mass index (BMI), smoking, alcohol consumption, and coffee drinking) and serum concentrations of testosterone, estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS). Among 52 healthy, elderly Greek men, we observed that serum levels of DHEAS decreased with increasing age [19% decline per 5-year increase in age, 95% CI, -2.1-(-33.5)], obesity [48% decline for BMI30 kg/m2 compared to27 kg/m2, CI, -15.7-(-68.7)], and current smoking [37% decline compared to nonsmokers, CI, -9.5-(-57.2)]. Estradiol concentrations increased with increasing BMI [77.1% increase for BMI30 kg/m2 compared to27 kg/m2, CI, -12.0-256.3], alcohol drinking [66% increase foror = 7 glasses/week compared to7 glasses/week, CI, 4.4-164.4], and coffee drinking [59% increase foror = 14 cups/week compared toor = 14 cups/ week, CI, -0.5-155.9], and decreased among current smokers [40% decline compared to nonsmokers, CI, -64.9-0.8]. SHBG was marginally positively associated with increasing age [13% increase per 5 years, CI, -0.5-29.6]. Testosterone was significantly related only to current smoking [27% decline compared to nonsmokers, CI, -45.4-(-3.1)]. These findings suggest that several variables appear to be associated with sex steroid levels and the influence of these findings on the occurrence of hormone-related conditions warrants further exploration.

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.

We evaluated the association of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) with risk of breast cancer in a study of 94 cases of premenopausal ductal carcinoma in situ and 76 controls. Compared with women in the lowest tertile of IGF-I, women in the upper two tertiles of IGF-I had an elevated risk for ductal carcinoma in situ. Conversely, compared with women in the lowest tertile of IGFBP-3, women in the upper two tertiles of IGFBP-3 had a decreased risk for ductal carcinoma in situ. After grouping women on the basis of both IGF-I and IGFBP-3, women in the highest two tertiles of IGF-I and the lowest tertile of IGFBP-3 were at notably higher risk than women in the lowest tertile of IGF-I and the highest two tertiles of IGFBP-3 (odds ratio = 3.7; 95% confidence interval = 1.1-12.2). We conclude that the combination of high IGF-I and low IGFBP-3 may increase the risk of premenopausal ductal carcinoma in situ.

Epidemiological studies of in situ breast cancer are sparse, and the role of reproductive history, an established risk modifier for invasive breast cancer, remains incompletely investigated. To examine possible associations with parity and age at first birth, we undertook a case-control study nested in a nationwide cohort of Swedish women. The reproductive history of 1,368 women aged 65 or younger with a diagnosis of carcinoma in situ of the breast were compared with that of 6,837 age-matched controls drawn randomly from a population-based Fertility Registry. Statistical analyses were performed by conditional logistic regression. Compared to nulliparous women, ever-parous women were at a reduced risk of carcinoma in situ of the breast. The risk decreased with number of live births, with the estimated risk reduction in the highest parity group (5+), being of the same magnitude as that reported for invasive breast cancer. By contrast, a positive association with increasing age at first birth was somewhat less pronounced than that observed previously in the same data set with respect to invasive breast cancer. Our findings indicate that parity affects the risk of invasive breast cancer and carcinoma in situ similarly, whereas the effect of age at first birth appears to be weaker for the risk of carcinoma in situ.

Family history (FH) is an important indicator of a woman's future risk of developing breast cancer. Using data collected in a large population-based case-control study (6705 cases and 9341 controls), we examined the associations of breast cancer with known risk factors in women reporting a first-degree FH (mother or sister), with an emphasis on lifestyle determinants that may be altered to reduce risk. First-degree FH was reported by 18.4% (n = 1234) of cases and 11.3% (n = 1058) of controls; the overall relative risk (RR) for breast cancer associated with a positive history was 1.70 [95% confidence interval (CI), 1.55-1.87] and 2.34 (95% CI, 1.80-3.02) for breast cancer at age 45 years or younger. Among women with a FH, statistically significant inverse associations were observed for increasing parity (RR per birth = 0.90; P0.0001), intake of carotene-rich foods (RR for2000 IU/day = 0.73; P = 0.02), and strenuous activity as a young adult (RR per episode/week = 0.93; P = 0.02). Recent alcohol consumption increased risk (RR per 13 g/week = 1.21; P = 0.02), as did weight gain during adult life in postmenopausal women (RR per 5 kg = 1.08; P = 0.001). Breast-feeding for any duration was associated with a lower RR in parous, premenopausal women (RR = 0.59; P = 0.04). Associations for most risk factors with breast cancer were similar among women with and without a FH of breast cancer; however, a stronger inverse association was observed for parity in women with a positive history (P for interaction = 0.04). Based on these data, women with a FH may reduce their excess risk of breast cancer through adjustments in lifestyle and reproductive choices. The risk associated with FH of breast cancer seems to be largely independent of other known risk factors.