Abstract
Cancers arise from the accumulation of somatic genome mutations, which can be influenced by inherited genomic variants and external factors such as environmental or lifestyle-related exposure. Due to the heterogeneity of cancers, precise information about the genomic composition of germline and malignant tissues has to be correlated with morphological, clinical and extrinsic features to advance medical knowledge and treatment options. With global differences in cancer frequencies and disease types, geographic data is of importance to understand the interplay between genetic ancestry and environmental influence in cancer incidence, progression and treatment outcome. In this study, we analyzed the current landscape of oncogenomic screening publications for geographic information content and quality, to address underrepresented study populations and thereby to fill prominent gaps in our understanding of interactions between somatic variations, population genetics and environmental factors in oncogenesis. We conclude that while the use of proxy-derived geographic annotations can be useful for coarse-grained associations, the study of geo-correlated factors in cancer causation and progression will benefit from standardized geographic provenance annotations. Additionally, publication-derived geographic provenance data allowed us to highlight stark inequality in the geographies of cancer genome profiling, with a near lack of sizable studies from Africa and other large regions.
Highlights
Cancer is one of the top causes of mortality globally, and the understanding of its genesis and pathophysiological mechanisms remains one of the major challenges in life sciences
Whereas the majority of oncogenomic variants arise as mutations in the DNA of somatic cells and affect genes involved in proliferation, differentiation and control of apoptosis, inherited (‘germline’) genomic variants can predispose to specific malignancies [1, 2]
Well-known examples here are the population-specific enrichment of BRCA1 gene variants in persons of Ashkenazi jewish ancestry compared to mixed-reference populations [6]; the higher somatic mutation frequencies for TP53, EP300 and NFE2L2 in Chinese patients suffering from esophageal squamous cell carcinoma (ESCC) compared to ‘Caucasian’ patients [7] or the significant molecular differences existing between prostate cancers in ‘African Americans’ vs. ‘Caucasicans’ (SPINK1 overexpression, ERG rearrangement and PTEN deletion are less frequent in the first group)[8]
Summary
Cancer is one of the top causes of mortality globally, and the understanding of its genesis and pathophysiological mechanisms remains one of the major challenges in life sciences. The past decades have witnessed major improvements in cancer diagnostics and therapeutics—partially driven by rapid advances in genomic screening techniques such as DNA array and sequencing. Whereas the majority of oncogenomic variants arise as mutations in the DNA of somatic cells and affect genes involved in proliferation, differentiation and control of apoptosis, inherited (‘germline’) genomic variants can predispose to specific malignancies [1, 2]. Well-known examples here are the population-specific enrichment of BRCA1 gene variants in persons of Ashkenazi jewish ancestry compared to mixed-reference populations [6]; the higher somatic mutation frequencies for TP53, EP300 and NFE2L2 in Chinese patients suffering from esophageal squamous cell carcinoma (ESCC) compared to ‘Caucasian’ patients [7] or the significant molecular differences existing between prostate cancers in ‘African Americans’ vs. ‘Caucasicans’ (SPINK1 overexpression, ERG rearrangement and PTEN deletion are less frequent in the first group)[8]
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