Background: Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer. Methods: We conducted a nested case–control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided. Results: Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218–240 ng/mL] versus 214 ng/mL [95% CI = 208–221 ng/mL]; P = .02) and IGFBP-3 (2611 ng/mL [95% CI = 2518–2704 ng/mL] versus 2498 ng/mL [95% CI = 2437–2560 ng/mL]; P = .04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (P_{for trend} = .02) and IGFBP-3 (P_{for trend} = .03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (P_{for trend} = .01), whereas the risk associated with increased IGFBP-3 was lower (P_{for trend} = .44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin. Conclusions: Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer.

OBJECTIVE—To investigate whether hyperglycemia is associated with increased cancer risk. RESEARCH DESIGN AND METHODS—In the Västerbotten Intervention Project of northern Sweden, fasting and postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements. RESULTS—Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09–1.47) (P_trend <0.001) and 1.31 (1.12–1.52) (P_trend = 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32–2.36) and 1.63 (1.26–2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92–1.27) (P_trend = 0.25) and 0.98 (0.83–1.16) (P_trend = 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23–5.45) (P_trend = 0.006), 1.86 (1.09–3.31) (P_trend = 0.02), 1.69 (0.95–3.16) (P_trend = 0.049), and 2.16 (1.14–4.35) (P_trend = 0.01), respectively. Adjustment for BMI had no material effect on risk estimates. CONCLUSIONS—The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer.

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte‐derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case‐control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C‐peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3‐fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44–5.12) for top vs. bottom quartile (p_trend = 0.008). The corresponding OR for C‐peptide was 1.81 (95% CI = 0.67–4.86; p_trend = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C‐peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity‐induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.

Meredith Yeager and colleagues with the Cancer Genetics Markers of Susceptibility (CGEMS) initiative report a new association to prostate cancer at chromosome 8q24. This defines a new locus, region 4, which shows association to prostate cancer susceptibility independent of previously reported associations at 8q24. We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 × 10−10, heterozygote OR = 1.17, 95% CI 1.10–1.24; homozygote OR = 1.33, 95% CI 1.21–1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24.

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case–control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA). In the National Prostate Cancer Register of Sweden Follow-up Study, a nationwide cohort, we identified 6849 patients aged 70 years or younger. Inclusion criteria were diagnosis with local clinical stage T1–2 prostate cancer from January 1, 1997, through December 31, 2002, a Gleason score of 7 or less, a serum PSA level of less than 20 ng/mL, and treatment with surveillance (including active surveillance and watchful waiting, n = 2021) or curative intent (including radical prostatectomy, n = 3399, and radiation therapy, n = 1429). Among the 6849 patients, 2686 had low-risk prostate cancer (ie, clinical stage T1, Gleason score 2-6, and serum PSA level of <10 ng/mL). The study cohort was linked to the Cause of Death Register, and cumulative incidence of death from prostate cancer and competing causes was calculated. For the combination of low- and intermediate-risk prostate cancers, calculated cumulative 10-year prostate cancer–specific mortality was 3.6% (95% confidence interval [CI] = 2.7% to 4.8%) in the surveillance group and 2.7% (95% CI = 2.1% to 3.45) in the curative intent group. For those with low-risk disease, the corresponding values were 2.4% (95% CI = 1.2% to 4.1%) among the 1085 patients in the surveillance group and 0.7% (95% CI = 0.3% to 1.4%) among the 1601 patients in the curative intent group. The 10-year risk of dying from competing causes was 19.2% (95% CI = 17.2% to 21.3%) in the surveillance group and 10.2% (95% CI = 9.0% to 11.4%) in the curative intent group. A 10-year prostate cancer–specific mortality of 2.4% among patients with low-risk prostate cancer in the surveillance group indicates that surveillance may be a suitable treatment option for many patients with low-risk disease.