Measuring childhood cancer late effects: evidence of a healthy survivor effect

Introduction

Given considerable focus on health outcomes among childhood cancer survivors, we aimed to explore whether survivor bias is apparent during long-term follow-up of childhood cancer survivors.

Methods

We identified all 1-year survivors of cancer diagnosed before 20 years of age in Denmark, Finland, Iceland, and Sweden. From the general population, we randomly sampled a comparison cohort. Study individuals were followed for hospitalizations for diseases of the gastroenterological tract, endocrine system, cardiovascular system, or urinary tract from the start of the cancer registries to 2010. We estimated cumulative incidence with death as competing risk and used threshold regression to compare the hazards of the diseases of interest at ages 20, 40, 60, and 75 years.

Results

Our study included 27,007 one-year survivors of childhood cancer and 165,620 individuals from the general population. The cumulative incidence of all four outcomes was higher for childhood cancer survivors during early adulthood, but for three outcomes, the cumulative incidence was higher for the general population after age 55 years. The hazard ratios (HRs) decreased for all outcomes with increasing age, and for two of the outcomes, the hazards were higher for the general population at older ages (endocrine diseases: age-specific HRs = 3.0, 1.4, 1.0, 0.87; Cardiovascular diseases: age-specific HRs = 4.1, 1.4, 0.97, 0.84).

Conclusions

Our findings provide empirical evidence that survivor bias attenuates measures of association when comparing survivors with the general population. The design and analysis of studies among childhood cancer survivors, particularly as this population attains older ages, should account for survivor bias to avoid misinterpreting estimates of disease burden.

     

Milk intake in early life and risk of advanced prostate cancer

The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.     

Transgenic mouse models of breast cancer

Summary Although valuable initial information can be gathered about transformation fromin vitro studies, human cancer occurs in the context of a complex interaction with its environment and must ultimately be studied in living animals. Transgenic animal models have been used to study breast transformation for a number of years and have yielded valuable information on the subject. In this paper, we will summarize results from our laboratories, and others, regarding the use of transgenic mice to study breast tumorigenesis. We will also suggest future directions for the use of transgenic models to understand, and hopefully, one day to cure the disease. Note: genes are referred to as lowercase names in italics (e.g.myc) and their protein products as uppercase (e.g. Myc).     

Diet,pregnancy, and lactation: Effects on adipose tissue,lipoprotein lipase,and fat cell size

Adipose tissue fat cell size and lipoprotein lipase (LPL) activity were determined in the retroperitoneal and subscapular depots of nonpregnant, pregnant, and postpartum rats fed either a standard laboratory diet or a high-fat diet containing 55% fat by wieght. High-fat feeding for 20 days increased, in nonpregnant rats, fat cell size and LPL activity two-to threefold in both depots. In pregnant rats at term, fat cell size was increased and LPL activity was depressed in both dietary groups. Twenty days postpartum, both retroperitoneal fat cell size and LPL activity were decreased in proportion to the size of the litter. Rats not allowed to lactate had fat cell sizes and LPL activity that were not significantly different than in nonpregnant controls. Fat cell size and LPL activity in rats nursing four pups were reduced to 77% and 36% of control, respectively. Those nursing a normal-sized litter of eight pups demonstrated a further reduction of fat cell size to 38% and of LPL activity to 2% of nonpregnant control values. High-fat feeding and obesity did not prevent the fat loss and decreased LPL activity associated with lactation; fat cell size was decreased to 61% and LPL activity to 3% of control values. Values for the subscapular depot followed essentially the same pattern as that observed for the retroperitoneal depot. Mammary LPL activity was increased more than tenfold in animals nursing four or eight pups compared with values at term, whereas no activity was detected in rats not allowed to lactate.     

Adenocarcinoma of the prostate in Iceland: a population-based study of stage, Gleason grade, treatment and long-term survival in males diagnosed between 1983 and 1987

OBJECTIVE: To investigate adenocarcinoma of the prostate in a single population with an extended follow-up period. MATERIAL AND METHODS: Using the Icelandic Cancer Registry, we identified all Icelandic men diagnosed with prostate cancer between 1983 and 1987. Disease stage, initial treatment and follow-up information were obtained from hospital records and death certificates. A critical evaluation was made of the accuracy of the death certificates regarding prostate cancer. All available histology information was reviewed and graded according to the Gleason grading system. RESULTS: A total of 414 men were diagnosed with adenocarcinoma of the prostate. Of these, 370 were alive at the time of diagnosis and stage could be determined. Four stage groups were defined: focal incidental (n=50); localized (n=164); local advanced (n=32); and metastatic disease (n=124). The mean age at diagnosis was 74.4 years (range 53-94 years). The combined Gleason score was 2-5 in 89, 6-7 in 117, 8-10 in 117 and unknown in 47 cases. The median follow-up period for the group was 6.15 years (range 0.3-19.8 years). Thirty men received treatment with curative intent: radiation therapy, n=20; and radical prostatectomy, n=10. A total of 334 patients died during the follow-up period, of whom 168 (50%) died of prostate cancer. Prostate cancer-specific survival at 10 and 15 years was 100% and 90.6%, respectively for focal incidental cancer; 73.1% and 60.8% for men with localized disease; 23.4% and 11.7% for local advanced disease; and 6.81% and 5.45% for metastatic disease. A Cox multivariate analysis showed age, stage and Gleason score to be independent predictors of prostate cancer death. A total of 104 patients with localized disease and a Gleason score of 相似文献