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Tumor Profiling in Relation to Cancer Etiology

The recognition of cancer as a heterogeneous disease, coupled with technological advances in molecular/genomic profiling of tumors, provides epidemiologists with the opportunity to integrate tissue profiling into etiologic studies to study the carcinogenic process, and pinpoint specific factors associated with risk for developing specific molecular or genomic cancer subtypes. This work is already underway in a number of existing cohort studies, including the Prostate, Lung, Colorectal, Ovarian Screening Trial (PLCO). Learn more about the biological samples available through PLCO.

In October 2018, the National Cancer Institute convened a group of experts to discuss the current state of the science of mutational signatures in cancer research and related opportunities and challenges. Read the Executive Summary of the Tumor Signatures Meeting.

DCEG investigators are undertaking foundational research to identify novel molecular and genomic signatures in tumors that are linked to germline genetic variants and key environmental exposures. We expect this approach will allow the identification of new risk factors and yield novel insights into biological mechanism of carcinogenesis.

Examples of specific studies include:

Biliary Cancer

Tumor tissue collected from populations in China and Chile are being used to examine the genomic landscape of cancer at different sites in the biliary tract and to look for potential molecular subtypes. A better understanding of the genetic and molecular differences across these malignancies can lead to more precise diagnoses and effective treatments, as well as providing clues as to etiology.

Bladder Cancer

Molecular pathology investigations of bladder tumors are ongoing in the New England Bladder Cancer Study using collected tumor DNA and tissue microarrays. Analyses to characterize important molecular alterations in tumors are in progress and are being integrated with germline genetic variation as well as environmental and occupational exposures to provide insight into the mechanisms of bladder carcinogenesis.

Breast Cancer

Analyses of risk factors measured by questionnaires, genotyping and blood/urine biomarkers in relation to molecular characteristics of breast cancer tumors and adjacent benign breast tissues, and clinical outcomes in the Polish Breast Cancer Study and Ghana Breast Cancer Study.

Large-scale evaluation of how genetic and environmental risk factors, molecular tumor characteristics and clinical progression interrelate in the Breast CAncer STratification (BCAST) Project.

Studies of breast tissues, risk factors, clinical data, breast density, blood or saliva for germline DNA to identify distinct molecular alterations in tumors and adjacent benign breast tissues among Asian women and to examine the associations of molecular changes with genetic and environmental risk factors, breast tissue composition and density, and breast cancer subtypes.

Characterizing the radiologic, histologic, and molecular features of dense breast tissue among women referred for diagnostic breast biopsy following an abnormal mammogram in the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project.

Conducting molecular and histomorphometric analyses of breast tissues in relation to mammographic density and breast cancer outcomes among breast cancer patients diagnosed within a general community health care plan.

Molecular epidemiologic studies of Terminal Duct Lobular Unit Involution of the Normal Breast are being conducted in collaboration with the Susan G. Komen® Tissue Bank.

Kidney Cancer

Intra-tumor heterogeneity and tumor evolution are being studied in kidney cancer histological subtypes based on whole-genome sequencing, deep target sequencing, whole genome methylation and SNP array analyses.

Lung Cancer

A large population-based case-control study of lung cancer, in the Lombardy region of Italy, designed to investigate the genetic and environmental determinants of lung cancer, and their influence on risk for individual molecular subtypes.

Sherlock-lung is a comprehensive study that aims to trace lung cancer etiology in never smokers by analyzing genomic data in tumor and surrounding lung tissue.


Converging lines of evidence suggest that melanoma comprises biologically distinct subtypes. DCEG investigators are undertaking tissue-based and genomic studies to provide a comprehensive classification of primary melanomas and the molecular changes associated with metastatic potential.

Ovarian and Endometrial Cancer

Analyses of biomarkers in DNA (somatic changes), cryopreserved blood cells, serum/plasma, and urine in relationship to cancer risk and clinical outcomes in a population of women in Poland.

Signatures of Radiation- and Chemotherapy-Induced Carcinogenesis

Second cancers may occur as a late adverse effect of radiotherapy and certain systemic therapies for first primary cancer. We are evaluating whether the molecular profiles of treatment-related cancers differ from those of sporadic tumors to identify whether there are signatures of radiation- and chemotherapy-induced carcinogenesis.

Thyroid Cancer

Evaluation of genomic, transcriptomic, and epigenomic landscapes of radiation-related papillary thyroid cancers in a cohort exposed to Chernobyl fallout in Ukraine.

Upper Gastrointestinal Cancer

Identification of somatic genetic alterations, including changes that might serve as early detection biomarkers for cancers of the upper gastrointestinal tract in a population in Shanxi Province, China.

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