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A novel method for identifying settings for well-motivated ecologic studies of cancer.

ABSTRACT: A low within-country variability and a large between-country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within- and between-country variability of cancer incidence to motivate high-quality ecologic studies. We extracted age-standardized incidence rate estimates (world standard population) from 135 regions for the ten most frequent invasive cancers in Europe for non-Hispanic white populations from Cancer Incidence in Five Continents, Volume X. We fitted weighted multilevel Poisson regression models with random country effects for each cancer and sex. We estimated intraclass correlation coefficients (ICCs) and 95% confidence intervals (95% CIs). A high ICC indicates a low within- and a high between-country variability of rates. The two cancer sites with the highest ICC among men were prostate cancer (0.96, 95% CI: 0.92-0.99) and skin melanoma (0.78, 0.64-0.93). Among women, high ICCs were observed for lung cancer (0.84, 0.73-0.95) and breast cancer (0.80, 0.69-0.91). The two most prominent sex differences for ICC occurred for cancers of the head and neck (men: 0.70, 0.55-0.85, women: 0.19, 0.08-0.30) and breast cancer (men: 0.04, 0.01-0.07, women: 0.80, 0.69-0.91). ICCs were relatively low for pancreatic cancer (men: 0.23, 0.10-0.35; women: 0.13, 0.04-0.21) and leukemia (men: 0.12, 0.04-0.21; women: 0.08, 0.02-0.14). For cancers with high ICC for which systematic factors of the health care system, screening and diagnostic activities are not plausible explanations for between-country variations in incidence, cross-country sex-specific ecologic studies may be especially promising.

SUBMITTER: Stang A

PROVIDER: S-EPMC4976447 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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A novel method for identifying settings for well-motivated ecologic studies of cancer.

Stang Andreas A Kowall Bernd B Rusner Carsten C Trabert Britton B Bray Freddie F Schüz Joachim J McGlynn Katherine A KA Kuss Oliver O

International journal of cancer 20151210 8

A low within-country variability and a large between-country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within- and between-country variability of cancer incidence to motivate high-quality ecologic studies. We extracted age-standardized incidence rate estimates (world standard population) from 135 regions for the ten most frequent invasive cancers in Europe for non-Hispanic white populati ...[more]

PMID: 26595447

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Project description:BACKGROUND: With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements. RESULTS: The simulations results show that the proposed index is not substantially affected by the sample size of the study and the censoring. They also show that its separability performance is higher than indices of predictive accuracy relying on the likelihood function. A simulated example illustrates the good operating characteristics of our index. In addition, we demonstrate that it is linked to the score statistic and possesses a biologically relevant interpretation.The practical use of the index is illustrated for identifying genes with common effects across eight independent genomic cancer studies of different sample sizes. The meta-selection allows the identification of four genes (ESPL1, KIF4A, HJURP, LRIG1) that are biologically relevant to the carcinogenesis process and have a prognostic impact on survival outcome across various solid tumors. CONCLUSION: The proposed index is a promising tool for identifying factors having a prognostic impact across a collection of heterogeneous genomic datasets of various sizes.

Dataset Information

A novel method for identifying settings for well-motivated ecologic studies of cancer.

Publications

A novel method for identifying settings for well-motivated ecologic studies of cancer.

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