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BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)

Background:The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.Methods and Findings:In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.Conclusions:Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.Please see later in the article for the Editors' Summary.

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Funding Cancer Research UK.

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p

Although anemia is widely considered an early sign of malignant disease, little is known about the pattern of hemoglobin decline before diagnosis. As an approach to understanding the duration of the preclinical phase of different types of malignant diseases, we investigated prediagnostic hemoglobin concentration changes in a large cohort of blood donors. Using a nested case-control design, we analyzed a population-based cohort comprising 1.1 million Scandinavian blood donors with complete follow-up through record linkage to population and cancer registers. A total of 16,375 cancer cases were identified, for whom we selected 161,995 controls. We used conditional logistic regression to estimate the risk of cancer in relation to hemoglobin concentration during the 5 years preceding the cancer diagnosis. Hemoglobin concentration decline began already 3 years before diagnosis of stomach cancer, multiple myeloma, and lymphatic leukemia; 2 years before diagnosis of small intestinal and colon cancer as well as of Hodgkin lymphoma. A decline was evident during the last year for non-Hodgkin lymphoma and myeloid/monocytic leukemia, whereas no change was found for cancer of the esophagus, breast or prostate. In conclusion, in this study, we have demonstrated that the pattern of declining hemoglobin concentration before cancer diagnosis varies considerably between malignancies without being a suitable screening tool for any of them. For some malignancies, however, the long duration of hemoglobin decline before clinical diagnosis suggests a substantial lead-time with systemic effects, during which earlier diagnosis should be achievable by emerging diagnostic tools. © 2009 UICC.

Background The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods Individual data on 53297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% CI] in current users 1.24 [1.15-1.33], 2p

The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use oi hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time: the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere,I are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiologi cal evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 rears after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diag nosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to reexamine the worldwide evidence. RI Ranstam, Jonas/A-4386-2009; Colditz, Graham/A-3963-2009

Background Women with breast cancer are at high risk of bilateral breast cancer. We aimed to assess the incidence of bilateral breast cancer in relation to age and time since diagnosis of first cancer. Methods We analysed a population-based cohort of 123757 women with a first primary breast cancer diagnosed in Sweden from 1970 to 2000 for frequency of bilateral breast cancers and deaths by means of record linkage. Second primary breast cancers were categorised as synchronous bilateral breast cancers if diagnosed within 3 months of the first primary cancer or as metachronous if diagnosed more than 3 months after diagnosis of first primary cancer. Findings We identified 6550 women who had developed bilateral breast cancer. Age-incidence patterns of synchronous and unilateral breast cancer were similar, although the absolute rates of synchronous bilateral cancer were 50-100 times lower than those of unilateral cancer. A woman aged 80 years or older is at least twice as likely to be diagnosed with synchronous bilateral breast cancer than is a woman younger than 40 years. In the first 20 years after diagnosis of primary breast cancer, incidence of metachronous bilateral cancer decreased from about 800 per 10(5) person-years to 400 per 10(5) person-years in patients diagnosed with primary breast cancer before the age of 45 years, whereas incidence remained at 500-600 per 10(5) person-years in those age 45 years or older at diagnosis. After 30 years’ follow-up, cumulative risk of metachronous bilateral breast cancer was about 15% irrespective of age at first primary breast cancer. Interpretation The higher than expected risk of synchronous bilateral breast cancer could be explained by non-genetic factors. By contrast, incidence of metachronous bilateral cancer fits neither a model of highly penetrant genes nor aggregation of environmental risk factors.

Background: There is substantial evidence that higher levels of activity reduce the risk of mortality, but several research questions remain about the protective effect of physical activity. We aimed to quantify the effect of physical activity on overall mortality in younger women and to assess the effect of past versus current activity. Methods: During 1991-1992, we enrolled 99,099 women, age 30-49 years, from the entire country of Norway and one Swedish region, in a population-based cohort study. The women provided information on physical activity level at age 14 and 30 years and at enrollment, as well as information on other personal characteristics at enrollment. We achieved complete follow-up into 2003 using record linkages to nationwide registers. We used Cox proportional hazard models to calculate multivariate relative risks (RRs) of dying from any cause. Results: During an average 11.4 years of follow-up, 1,313 women died. Risk of death decreased with increasing physical activity at enrollment (5 categories; P for trend < 0.0001) and was reduced by half in the highest compared with the lowest category (RR = 0.46; 95% confidence intervals = 0.33-0.65). This protective effect was consistent across strata of age at entry, smoking, country, and education. After adjustment for physical activity at enrollment, activity at age 14 and 30 was not associated with mortality. Conclusions: Current physical activity substantially reduces mortality among women. This association is observed even with low levels of physical activity and is accentuated with increased physical activity.

Perinatal events and conditions, notably birth weight, are associated with breast cancer risk in offspring, and correlates of mammary gland mass are predictors of breast cancer risk. These findings may be interpreted as indicating that high levels of estrogens and components of the insulin-like growth factor system during pregnancy favour the generation of mammary tissue-specific stem cells, and that the number of these cells, which is positively associated with mammary gland mass, is an important determinant of breast cancer risk. Perinatal events and conditions may also affect risk for other malignancies, but the evidence in the case of breast cancer is prominent, possibly because estrogens and the insulin-like growth factor system are both involved in breast cancer etiology and affect birth weight.

In this review, issues of causality in epidemiologic research with emphasis on the aetiology of human cancer are considered. Principles of assessing causation in epidemiological studies of cancer are distinguished into those concerning an individual study, several studies and a particular person. Strengths and weaknesses of various approaches of documenting carcinogenicity in humans are examined and lists of major established causes of human cancer are presented. The review concludes with estimates of mortality from cancer around the world that can be attributed to specific factors under the light of the current scientific knowledge.

Objective To determine whether exposure to low doses of ionising radiation in infancy affects cognitive function in adulthood. Design Population based cohort study. Setting Sweden. Participants 3094 men who had received radiation for cutaneous haemangioma before age 18 months during 1930-59. Main outcome measures Radiation dose to frontal and posterior parts of the brain, and association between dose and intellectual capacity at age 18 or 19 years based on cognitive tests (learning ability, logical reasoning, spatial recognition) and high school attendance. Results ne proportion of boys who attended high school decreased with increasing doses of radiation to both the frontal and the posterior parts of the brain from about 32% among those not exposed to around 17% in those who received >250 mGy. For the frontal dose, the multivariate odds ratio was 0.47 (95% confidence interval 0.26 to 0.85; P for trend 0.0003) and for the posterior dose it was 0.59 (0.23 to 1.47; 0.0005). A negative dose-response relation was also evident for the three cognitive tests for learning ability and logical reasoning but not for the test of spatial recognition. Conclusions Low doses of ionising radiation to the brain in infancy influence cognitive abilities in adulthood.

Objective Because oral contraceptives are so widely used, any health consequences may have substantial public health implications. Whether pregravid oral contraceptives could affect subsequent pregnancies has not been adequately studied. The study objectives were to examine whether pregravid oral contraceptive use affects fetal growth and pregnancy hormone levels. Design A prospective study of pregnant women followed through pregnancy. Setting A major teaching hospital in Boston, USA. Population Two hundred and sixty Caucasian pregnant women, with a mean age of 31, and a parity of no more than two. Seventy-nine percent of the women were pregravid oral contraceptive users. Methods Exposure and covariate data were collected through structured questionnaires. Blood was drawn for hormonal analysis during the 16th and 27th gestational week. Information on pregravid oral contraceptive use included duration and recency of use, and oral contraceptive formulation. Multivariate regression models were used to examine the effect of pregravid oral contraceptive use on birth outcomes and the studied pregnancy hormones. Main outcome measures Birthweight, placental weight, gestational age, pregnancy hormone levels of oestriol and progesterone at 16th and 27th gestational week. Results Adjusting for confounders, pregravid oral contraceptive use increased birthweight (mean difference +207.3 g, 95% CI = +77.6 to +337.1) and placental weight (mean difference = +64.9 g, 95% CI = +13.0 to+116.9) compared with never use. Women with prior oral contraceptive use had higher levels of serum progesterone (P = 0.002) and oestriol (P = 0.12) at the 27th gestational week measurement. The effect on birthweight, placental weight and hormones was stronger among those using oral contraceptives in the previous year and those using a high progestin/high oestrogen potency preparation. Conclusions Pregravid oral contraceptive use is positively associated with fetal growth, and this effect may be mediated through oestriol and progesterone.

Background There has been renewed interest about determinants of birth size following the propagation of hypotheses that birth size parameters may have long-term consequences on the occurrence of common diseases in adulthood, including breast cancer. Methods In the context of a cohort study, 296 Caucasian pregnant women in Boston, USA and 329 Chinese pregnant women in Shanghai, China were followed to term. Birth size characteristics of the baby and maternal anthropometry were measured using standardized protocols. Analyses were conducted through multiple regression procedures. Results No significant difference was found between US and Chinese newborns with respect to gestational age. Among US women, pregravid oral contraceptive use was strongly associated with higher birthweight. In both US and Chinese women, birthweight was positively associated with height, pre-pregnancy body mass index, and weight gain during pregnancy. More importantly, the difference in these three maternal variables between the two samples fully explains the birthweight difference between the two populations. Conclusions We postulate that babies in China may have lower birthweight because their mothers’ anthropometry imposes constraints on the growth of the fetus. When Chinese women migrate to the US, they tend to grow taller and heavier so that their babies can reach, on the average, a higher birthweight. The recurrence of this process in successive generations could explain why eventually Chinese Americans tend to have comparable birth and adult anthropometric characteristics, as well as comparable breast cancer rates, to those of Caucasian Americans.

BACKGROUND: Although sun exposure is an established cause of cutaneous malignant melanoma, possible interactions with host factors remain incompletely understood. Here we report the first results from a large prospective cohort study of pigmentation factors and sun exposure in relation to melanoma risk. METHODS: The Women's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30-50 years in 1991 or 1992 when they completed an extensive questionnaire on personal characteristics and exposures. Linkages to national registries ensured complete follow-up through December 31, 1999. Poisson regression models were used to estimate relative risks (RRs). All statistical tests were two-sided. RESULTS: During an average follow-up of 8.1 years, 187 cases of melanoma were diagnosed. Risk of melanoma was statistically significantly associated with increasing body surface area (RR for > or =1.79 m2 versus < or =1.61 m2 = 1.60, 95% confidence interval [CI] = 1.03 to 2.48; P(trend) =.02), number of large asymmetric nevi on the legs (RR for > or =7 nevi versus 0 nevi = 5.29, 95% CI = 2.33 to 12.01; P(trend)

Objective: Because birth weight has been positively associated with adult life breast cancer risk and pregnancy estrogens have been hypothesized to affect breast cancer risk in the offspring, we have evaluated the association of pregnancy estriol ( E3), estradiol ( E2), progesterone and prolactin in maternal serum samples collected during the 16th and 27th gestational week with birth size parameters. Methods: Prospective study of 230 Caucasian women who delivered a live singleton after 37-42 weeks of gestation. Results: E3 at the 27th gestational week was significantly positively associated with birth weight, birth length and placental weight. Progesterone at the 27th gestational week was also significantly positively associated with birth weight and placental weight but, after mutual adjustment among the studied pregnancy hormones, these associations weakened considerably. There was also inconsistent evidence that SHBG and prolactin at the 27th gestational week may be respectively positively and inversely related with birth size parameters. Measurements during the 16th gestational week were generally unrelated to birth size parameters. Conclusions: Because E3 is a dominant estrogen during pregnancy, the positive association of it with birth weight allows the use of the latter as a proxy of in utero exposure to estrogens in breast cancer investigations.

OBJECTIVE: To assess pregnancy hormone levels in relation to nausea with or without vomiting. METHODS: In the context of a prospective cohort study, 262 white pregnant women in Boston were observed through delivery. Maternal blood was collected at 16 and 27 weeks’ gestation and serum levels of estradiol, estriol, progesterone, prolactin, and sex hormone-binding globulin were determined. Information on sociodemographic and medical variables was collected through an interviewer-administered questionnaire and review of medical records. At the 27th gestational week, nausea with or without vomiting at any time during the index pregnancy was ascertained. RESULTS: By the 27th gestational week, 209 women (79.8%) had experienced nausea with or without vomiting. There was a substantial and statistically significant (P

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other. (C) 2003 Lippincott Williams Wilkins.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women’s age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics. (C) 2002 Lippincott Williams Wilkins.

The recent progress in molecular biology and pharmacology has increased the likelihood that cancer prevention will rely increasingly on interventions collectively termed ‘chemoprevention’. Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. A number of potential targets for chemoprevention have recently been identified. Many classes of agents including antioestrogens, anti-inflammatories, antioxidants and other diet-derived agents have shown a great deal of promise. In this review, we will begin by describing the general classes of chemopreventive agents and the mechanisms by which these agents act. We will then describe the opportunities that presently exist for chemoprevention of specific cancers.

Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors. and the induction of immunosuppression, Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency. The associations between a selection of infectious agents and malignancies are covered in detail.

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. (C) 2001 Wiley-Liss, Inc.

Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation. the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency. The associations between a selection of infectious agents and malignancies are covered in detail.

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 ICF-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% CT 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. (C) 2000 Lippincott Williams & Wilkins.

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 [greater than or equal to 2 packs per day, odds ratio (OR) = 2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (greater than or equal to 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. Int. J. Cancer 85:498-502, 2000. (C) 2000 Wiley-Liss, Inc.

Objectives. To evaluate the nutritional etiology of benign prostatic hyperplasia (BPH) by conducting a case-control study in Athens, Greece. Despite the high morbidity and substantial human suffering produced by BPH, little research has been undertaken concerning the nutritional etiology of this disease, Methods. The study sample consisted of 184 patients with histologically confirmed BPH and 246 control patients without clinical evidence of prostate disease. All patients and controls were permanent residents of the greater Athens area. The data were modeled through unconditional logistic regression. Results. Among the food groups, fruits were inversely related to BPH risk, with a logistic regression-derived odds ratio of 0.79 per quintile increase and 95% confidence internal 0.67 to 0.93. Increased consumption of both butter and margarine was positively associated with BPH risk, and a marginally significant positive association was also evident for seed oils. No overall association was found with respect to consumption of olive oil. In analyses evaluating the role of nutrients rather than foods, zinc, an element selectively concentrated in the prostate gland, was significantly positively associated with BPH risk. Conclusions. Our study provides evidence that, among added lipids, butter and margarine may increase the risk of BPH, and fruit intake may reduce this risk. Dietary zinc may play an important role in the etiology of BPH. (C) 1999, Elsevier Science Inc.

Recent data suggest that the IGF system plays an important role in the pathogenesis of several farms 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 colarectal cancer, on the other. IGF-I, IGF-lt 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. (C) 1999 Wiley-Liss, Inc.

The causation of breast cancer in certain strains of mice by a vims that can be transmitted vertically, through the milk produced during lactation, has led to the hypothesis that a similar phenomenon could exist in humans. There have been laboratory based studies in humans suggesting that a virus may be involved in the etiology of female breast cancer although other investigations did not support this hypothesis Descriptive data and epidemiologic evidence of ecologic nature do not indicate a role of lactation in the causation of human breast cancer, but the hypothesis has not been adequately assessed in analytic epidemiologic studies, A nested case-control StUdy undertaken in Sweden to examine the role of prenatal factors on breast cancer risk in the offspring, allowed the evaluation of the importance of breast-feeding in the causation of this discase. Standardised records concerning women born at the Uppsala University Hospital from 1874 to 1954 were linked with invasive breast cancer incident cases, identified through their unique national registration number in the Swedish Cancer Registry during 1958-1990. For each case with breast cancer, the females born to the first three mothers admitted after the case’s mother were selected as potential matching controls. Only controls living in Sweden and free from breast cancer until the time of diagnosis of breast cancer in the corresponding case were eventually included in the study. The analysis was based on 458 cases of breast cancer born in singleton pregnancies and 1,197 singleton age- and birth date-matched controls. Breast-feeding was not a significant or suggestive risk factor for breast cancer in the offspring; compared to women who at discharge were wholly or partly breastfed, women who as nowborn were not breastfed has a relative risk of breast cancer of 0.97 with 95% confidence interval 0.44-2.17 (P=0.95).

Data from an international case-control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast-cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic-regression-adjusted odds ratio (OR) was 1.2 1, the 95% confidence interval (CI), 0.94 to 1.55. The OR was significantly elevated during the 15-year period following the latest multiple birth (1.76; CI, 1. 12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast-cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast-cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long-term reduction of breast-cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary-gland cells.

Pregnancy estrogens are substantially elevated in twin pregnancies and are likely to be more so in the case of dizygotic twins. If levels of pregnancy estrogens were positively related to breast cancer risk in the offspring, female twin members would be expected to be at slightly higher risk. Data from an international case-control study were utilized to assess this hypothesis. The analysis was based on 870 cases with breast cancer and 2,641 hospital controls from two sites: Glamorgan, Wales (1965-1967), and Boston, Massachusetts (1965-1966). Seventeen cases were members of twin pairs, and 8 of them had a twin brother; 33 controls were members of twin pairs and 14 had a twin brother. Among all women, the odds ratios for breast cancer were as follows: for twins with brothers, 1.54 (95% confidence interval (CI) 0-64-3.71); for twins with sisters, 1.30 (95% CI 0.58-2.92); and for all twins, 1.40 (95% CI 0.77-2.55). The odds ratios were higher among premenopausal women. These findings are not conclusive, but they are compatible with the hypothesis that pregnancy estrogens may affect the risk of breast cancer in the off spring.