The Bharat Cancer Genome Atlas: Charting India's Unique Cancer Landscape for Precision Oncology

Abstract

Development of the Bharat Cancer Genome Atlas (BCGA) is poised to be a comprehensive genomic database which will not only deepen our scientific understanding of the unique molecular landscape of cancers prevalent in India but also provide the essential foundation required to facilitate the development of targeted therapies, enable personalized treatment strategies, and foster the creation of more effective early detection methods specifically tailored for the Indian population. The open-access nature of the BCGA is a core strength, designed to democratize access to this vital information, thereby empowering researchers to make new discoveries, enabling clinicians to provide more precise care, and allowing patients and their families to engage more fully in their health journey.

Cancer represents a significant global health challenge, standing as one of the primary causes of mortality and morbidity worldwide. ¹ For India, which is home to over 17% of the global population, this challenge is particularly unique and large. India faces an immense and growing cancer burden with the current estimates suggesting that an individual in India has a lifetime risk of approximately 1 in 9 of developing cancer. ² This substantial risk is compounded by a rapidly aging population, a demographic shift that inherently increases the incidence of age-related diseases, including many forms of cancer and complicated by delayed detection ³ and advanced disease at diagnosis making it a significant public health problem.

India's population is characterized by unparalleled diversity. This diversity is compounded by stratification of the population into distinct endogamous groups with distinct genetic prevalences (IGVDB Consortium, 2008), ⁴ a wide spectrum of environmental exposures, and varying prevalence of genetic predispositions. These factors coupled with persistent challenges in equitable and affordable access to timely screening, early diagnosis and treatment, converge to create a unique cancer burden. In addition, some cancers in India exhibit unique geographical, ethnic, environmental and genetic underpinnings that makes them substantially different from those observed in many Western populations.

Cancer burden in India is staggering, with over a million new patients diagnosed annually. ² Emerging evidence suggests some cancers which are highly prevalent in India, are relatively rare elsewhere in the world. Examples include oral and head and neck cancers ⁵ and gallbladder cancer. ⁶ In many cases these cancers present distinct clinical and molecular characteristics that are not extensively studied highlighting the urgent and critical need for India-specific research initiatives to understand these cancers better.

Over the past two decades, research into cancer has witnessed transformative progress, largely driven by data-intensive discovery efforts centred around genomics. initiatives, and these have to a great extent revolutionized our understanding of the disease and paved the way for the development of targeted therapies. ⁷

However, with notable exceptions, this rapid progress in targeted therapies has largely been centered around and driven by genomic data primarily derived from Western populations. ⁸ While highly valuable, these often fall short in addressing the specific, environmental and genetic risk in Indian settings. It is now well-documented that the prevalence of specific biomarkers can differ significantly between populations. For instance, the prevalence of activating mutations in the Epidermal Growth Factor Receptor (EGFR) gene in lung cancer, shows significant differences in Indian patients compared to those reported elsewhere. ⁹ Similarly, the prevalence of pathogenic variants in the BRCA1 and BRCA2 genes, critical biomarkers for hereditary breast and ovarian cancers and targets for PARP inhibitors, is also different in India compared to what is reported from elsewhere. ¹⁰

An urgent need therefore exists for India to develop its own comprehensive genomic atlases, specifically tailored to prevalent cancer types, due to these differences. Such atlases are essential to enable the Indian population to fully benefit from existing and upcoming biomarker-driven therapies. Without this India-specific data, clinicians and patients in India may face challenges in selecting the most appropriate treatments based on global guidelines which may not accurately reflect the molecular landscape of cancers prevalent in the country. Furthermore, some cancers highly prevalent in India, such as head and neck cancers and gallbladder cancer, and those with unique geographical associations, often lack large-scale studies on biomarker prevalence estimates, though data on this is emerging. ¹¹ This deficit severely limits the ability to conduct biomarker driven clinical studies and trials specific to these cancers in India and restricts the potential use of approved biomarker-targeted therapies that might otherwise be beneficial, simply due to a lack of supporting data and established guidelines for the Indian context.

The Bharat Cancer Genome Atlas (BCGA) therefore represents an ambitious and critically important endeavor. Its core aim of the initiative is to build a comprehensive and open-access atlas for the genomic landscape of cancer specifically within India. This initiative is designed to address the significant data gap and to also provide a foundational resource for cancer research and clinical care tailored to the Indian population.

BCGA therefore envisages focused and collaborative efforts across multiple institutions and research groups throughout the country. The database currently indexes exome datasets for cancers, with a clear roadmap to include other genomic datasets including whole genome and transcriptome datasets currently being sequenced and analyzed. To ensure interoperability, the data resource is built on the cBioportal which offers seamless inter-operability and possibility to perform complex queries in-built. The resource is available online at https://bcga.iitm.ac.in The initiative also envisages meticulous collection and compilation of high-quality genomic sequencing data from representative and unique cancer cases across diverse geographical regions and ethnic groups within India. Currently the database hosts genomics datasets on breast cancer as well as head and neck cancer, with a clear roadmap to encompass other prevalent cancers including colorectal cancers as well as hematological malignancies by the end of the year. The initiative is designed to be inclusive, also envisaging the indexing and integration of existing cancer genomic datasets that have been published by researchers in India, thereby consolidating valuable information that may currently be fragmented and not available for analysis. The initiative has been working with partners to include datasets from published studies emerging from India encompassing other cancer types. Through these combined efforts, the BCGA seeks to identify and pinpoint the specific genetic mutations, structural variants, copy number alterations, and other molecular biomarkers that are associated with various cancer types prevalent in India. A particular focus is placed on gathering extensive data on cancers that are pertinent and highly prevalent in the Indian population but less common elsewhere, ensuring these unique challenges are adequately addressed.

The knowledge generated from the BCGA has the potential to be transformative for cancer research and cancer care in India. We anticipate that this comprehensive genomic data will pave the way for research into the potential utility of biomarker-targeted molecules, apart from identifying their effectiveness in additional cancer indications or patient subgroups for cancers prevalent in India. The atlas will serve as a powerful resource to drive the design and execution of clinical studies and trials within India, through making the prevalence of genetic variants available and enabling researchers to test novel therapies and evaluate existing ones specifically within the Indian population. Crucially, the data will contribute significantly to the development of newer targeted therapies that are specifically relevant to the molecular alterations common in Indian cancers. Beyond therapy, the BCGA data holds promise for improving early detection strategies by identifying potential genomic markers associated with increased risk or early-stage disease, and ultimately, leading to enhanced patient outcomes for prevalent cancers across the nation.

The BCGA is more than just a scientific endeavor focused on generating data. It is intricately linked to the aspiration for data-driven and evidence-based action to improve the lives of millions of Indians who have been affected by cancer. It therefore represents the ambition and a firm commitment to leveraging cutting-edge genomic technology and fostering widespread scientific collaboration to tackle a pressing public health challenge head-on. The initiative embodies a belief in the power of science and collaboration, and being deeply rooted in the principle of open data sharing to collectively improve human health and well-being.

A fundamental principle guiding the BCGA is its commitment to an open-access data model. This means that the vast amounts of genomic data generated and compiled under the BCGA umbrella will be made freely accessible to the wider research community, clinicians, and, where appropriate and ethically permissible, the public. We firmly believe that open data philosophy is a powerful engine for progress and it inherently promotes collaboration among researchers by removing barriers to access data thereby accelerating the pace of scientific discovery by allowing multiple groups to analyze the data from different perspectives and pursue diverse research questions simultaneously. Furthermore, the open access model democratizes access to crucial genomic information, making it available not just to large, well-funded institutions but also to smaller research groups, individual clinicians, and innovators across the country and globally. BCGA therefore aims to catalyze innovation in cancer research and development with an emphasis on relevance to India. There are many previous examples on how collective information access has demonstrably deepened our understanding of cancer's intricacies ¹² and we hope to emulate this in the Indian context towards development of novel diagnostic tools and therapeutic strategies that are not only effective but also accessible, affordable, and evidence-based for the Indian population. BCGA therefore would be a larger and open access complementary resource to the Indian Cancer Genome Atlas (ICGA) which has a regulated data access policy.

The benefits of an open-access data model extend significantly beyond the realm of fundamental research, but also comes with immediate application in patient-care. Clinicians can harness the power of the BCGA data to inform and possibly arrive at evidence-based treatment plans. Utilizing the aggregate prevalence of specific genetic variants and biomarkers within relevant patient populations captured in the atlas, clinicians can make informed decisions about selecting the most effective existing therapies for individual patients. This knowledge can help tailor treatment choices, potentially minimizing the risk of adverse effects associated with therapies through pharmacogenomics. The prevalence of actionable biomarkers indexed in BCGA can also inform evidence-based discussions about actionability for specific cancer types prevalent in India, apart from understanding their underlying genetic drivers. This increased access also has the potential to enable patients to participate more actively in shared decision-making regarding their care and enhance their engagement in the treatment process. This transparency and access to relevant population-level information can also play a vital role in alleviating the anxiety and uncertainty that often accompany a cancer diagnosis, providing patients and their families with a greater sense of understanding and control during what is frequently an overwhelming experience.

The creation and maintenance of a comprehensive initiative like the BCGA require not only significant scientific effort but also meticulous attention to practical and ethical considerations. Implementing a standardized process for data collection across potentially many different clinical sites is essential to ensure consistency and comparability of the generated data. Rigorous processes have been set to ensure data quality, processing, and analysis have been established and adhered to. In addition, the ethical considerations related to data privacy, patient confidentiality, and data security have also been addressed with care and foresight since we firmly believe that building and maintaining public trust in large-scale genomic data initiatives is foundational for their long-term success.

As part of the initiative's broader impact to bring a meaningful change, BCGA will in the future also significantly enrich the research and clinical community in India through focused training programs and educational workshops for researchers, bioinformaticians, genetic counselors, and clinicians to equip them with the requisite skills and knowledge to effectively interpret and utilize the vast genomic data generated by and indexed in BCGA in their research, clinical practice, and patient counseling. We firmly believe this capacity building is vital for translating the insights from the atlas into tangible improvements in patient care and fostering future generations of oncologists and cancer researchers in India.

BCGA is spearheaded by two premier organizations in India: Indian Institute of Technology Madras (IIT Madras) and Karkinos Healthcare. IIT Madras brings its renowned strength in academic research, its national cancer biobank and expertise which are essential for such a complex project. Karkinos Healthcare contributes its clinical network, scale in genomic data generation, and deep expertise and experience in applying genomics in a healthcare setting, addressing the pertinent clinical problems and facilitating the analysis of data and practical aspects of data collection and utilization. This collaboration, bringing together the best of academic research and clinical genomics capabilities, represents a powerful partnership poised to address the unique and prevalent challenges in cancer genomics facing India today and build a robust foundation for the future of precision oncology in the country.

In summary, the creation of the Bharat Cancer Genome Atlas is poised to be a comprehensive genomic database which will not only deepen our scientific understanding of the unique genomic landscape of cancers prevalent in India but also provide the essential foundation required to facilitate the development of targeted therapies, enable personalized treatment strategies, and foster the creation of more effective early detection methods specifically tailored for the Indian population. The open-access nature of the BCGA is a core strength, designed to democratize access to this vital information, thereby empowering researchers to make new discoveries, enabling clinicians to provide more precise care, and allowing patients and their families to engage more fully in their health journey.