Background The European Randomized study of Screening for Prostate Cancer (ERSPC) is a randomized multi-center trial with a predefined centralized database, analysis plan and core age group (55–69 years) evaluating prostate-specific antigen (PSA) testing in eight European countries. Methods The present results are based on prostate cancer (PCa) incidence and mortality truncated at 9, 11, and 13 years of follow-up in the intervention arm (offered PSA testing) relative to the control arm. A secondary analysis corrected for selection bias due to non-participation was performed. Because of incomplete follow-up, only incidence and no mortality data at 9 years follow-up are reported for the French centers. Findings The rate ratio (RR) of PCa incidence between the intervention and control arms was 1.91 after 9 years (1.64 including France), 1.66 after 11 years and 1.57 after 13 years. The RR of PCa mortality was 0.85, 0.78 and 0.79 at 9, 11 and 13 years respectively (95% confidence interval 13-year 0.69–0.91, p = 0.001). This corresponds to a relative risk reduction of 21% and an absolute risk reduction of death from PCa at 13 years of 0.11 per 1,000 person-years or 1.28 per 1,000 men randomized, which is equivalent to one PCa death averted per 781 men invited for screening or one per 27 additional PCa detected. PCa mortality reduction in screened men after adjustment for non–participation was 27%. Interpretation This update of ERSPC confirms a substantial PCa mortality reduction due to PSA testing, with a substantially increased absolute effect at 13 years compared to findings after 9 and 11 years. Funding All sources of funding per center are indicated in the “Web extra material” section. Trial identification This trial is registered under Current Controlled Trials number: ISRCTN49127736.

Objective To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas Design Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. Setting Nine European countries. Subjects 7148 cases of lung cancer and 14 208 controls. Main outcome measures Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m 3 ) of household air. Results The mean measured radon concentration in homes of people in the control group was 97 Bq/m 3 , with 11% measuring > 200 and 4% measuring > 400 Bq/m 3 . For cases of lung cancer the mean concentration was 104 Bq/m 3 . The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m 3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m 3 increase in usual radon-that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m 3 . The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m 3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. Conclusions Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Summary Background Several trials have evaluated the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PC) mortality, with conflicting results. We report on the mortality in the European Randomized Trial of Screening for Prostate Cancer (ERSPC) with two added years of follow-up. Methods The ERSPC is a randomized screening trial in men aged 50 – 74 years (N=182,160) at entry, with a predefined core age group of 55 – 69 years (N=162,388) conducted in eight European countries Men randomized to the intervention arm were offered prostate specific antigen (PSA)-based screening while those in the control arm were not offered screening. The primary outcome is PC mortality. Results After a median follow-up of 11 years the relative risk reduction for PC death in the intention to screen analysis was 21% (risk ratio 0.79, 95%CI 0.68 – 0.91, p=0.001), and 29% for screened men after correction for non-compliance in the core age group. The absolute difference in mortality amounted to 0.10 per 1000 person years or 1.07 per 1000 men randomized. The rate ratio of PC mortality during the follow-up years 10 -11 was 0.62 (95% CI 0.45 – 0.85, P=0.003). The numbers needed invite (NNI) and detect (NND) to prevent one PC death amounted to 1055 and 37 at 11 years of follow-up and 936 and 33 for the entire follow-up. There was no difference in all-cause mortality. Conclusions Two added years of follow-up consolidate our previous finding that PSA-based screening reduces PC mortality but does not affect all cause mortality. (The trial is registered in the ISRCTN registry under number 49127736.)

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Cancer Research UK, Medical Research Council.

Objectives To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Design Multinational retrospective cohort study of cancer mortality. Setting Cohorts of workers in the nuclear industry in 15 countries. Participants 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Main outcome measurements Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. Results The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv ( < 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. Conclusions These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Key words: prostate cancer; 25(OH)-vitamin D 3 ; serum bankVitamin D deficiency has been implicated as risk factor for prostate cancer. 1 In cell culture studies, vitamin D metabolites have had protective action against cancer development (for review see Ylikomi et al. 2 ). Normal and malignant prostate cells contain vitamin D receptor (VDR), 3-5 which mediates the antiproliferative action of 1,25(OH) 2 -vitamin D 3 . 6 In addition to the antiproliferative action of 1,25(OH) 2 -vitamin D 3 , it can cause apoptosis, 7 induce differentiation, 8 inhibit telomerase expression, 9 inhibit tumor cell invasiveness 10 and suppress tumor-induced angiogenesis. 11 Several epidemiologic studies have reported that high serum vitamin D levels or sunlight may protect against prostate cancer. 3,4,[12][13][14][15] Factors that affect prostate cancer include age, dark skin and environment, e.g., latitude and diet. 16 These factors might be linked to vitamin D availability. 17,18 Furthermore, high fish (rich in vitamin D) consumption appears to correlate with lower prostate cancer risk. 19 In addition, VDR gene polymorphism may contribute to the risk of prostate cancer. 20 -24 There is also a study showing no correlation between serum vitamin D metabolites and prostate cancer in Maryland (USA), 25 but the authors concluded that the power of their study was limited. In another study on U.S. male physicians, only a weak protection against prostate cancer was found with the highest quartile of serum 1␣,25(OH) 2 -vitamin D 3 . 26 Similarly, no correlation was found in Hawaii. 27 There are 2 physiologically interesting metabolites of vitamin D, 1␣,25(OH) 2 -vitamin D 3 , regulating calcium homeostasis for bones and muscles in extremely narrow limits, and 25(OH)-vitamin D 3 , regulating target (prostate) cell proliferation and differentiation through activation to 1␣,25(OH) 2 -vitamin D 3 in the target (prostate) cell. Serum 25(OH)-vitamin D 3 is produced by liver 25-hydroxylase, the rate of the synthesis being directly proportional to vitamin D 3 serum concentration. 28 Therefore, serum 25(OH)-vitamin D 3 reflects vitamin D availability in the organism. Serum concentration of 25(OH)-vitamin D 3 is so high that it might possess a significant biologic activity in target cells, but it is also a precursor for the biologically more active 1␣,25(OH) 2 -vitamin D 3 . Prostate as well as many other target organs can activate 25(OH)-vitamin D 3 through 1␣-hydroxylation 29,30 and inactivate it through 24-hydroxylation. 31 In an epidemiologic study, we found that low concentrations (Ͻ40 nmol/l) of 25(OH)-vitamin D in serum were associated with a 1.7-fold increased risk of prostate cancer. 3,4 Since the power of our study was limited, preventing extensive analysis of the data, and we are partners in the Nordic Specimen Banks for Cancer Causes and Control, we had an opportunity to extend our study to other Scandinavian countries located geographically at the same latitude. Our aim was to determine whether our finding could be replicated in a la...

Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages <75 in 13 European countries. Age-adjusted adenocarcinoma incidence rates increased throughout Europe, the rate of increase ranging from around 0.5% per annum in Denmark, Sweden, and Switzerland to z3% in Finland, Slovakia, and Slovenia.