Elsevier

Gene Reports

Volume 21, December 2020, 100832
Gene Reports

A decade in unravelling the etiology of gastric carcinogenesis in Kashmir, India – A high risk region

https://doi.org/10.1016/j.genrep.2020.100832Get rights and content

Highlights

  • For early detection of GC, the adoption of modern cancer screening programs in the Asian high-risk regions like Kashmir needs to be formulated.

  • To understand the molecular underpinning of GC, multicentric collaborative and conclusive studies like GWAS/WES are warranted.

  • This review summarises currently available results on various dietary, environmental and genetic factors studied in Kashmiri population .

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths globally. Although, understanding the molecular mechanisms leading to gastric carcinogenesis has gained much importance in the last few decades, yet biomarkers for early detection are not available so far. Kashmir valley- India, represents a high-risk cancer region, has unique dietary and sociocultural practices, which makes it an intriguing region for studying the etiology of gastric cancer. Although several studies have been carried out in Kashmir in the recent past to understand the role of genetic and/or environmental factors in the development of the disease, the complete etiology, and causes of the high incidence of this disease, yet remains unclear. This review summarises the currently available results on various dietary, environmental factors, and genetic factors studied in the Kashmiri population and their relevance with the global understanding of the disease.

Introduction

Although the incidence of gastric cancer (GC) is steadily declining, it remains one of the most common and deadly malignancies in the world. In accordance with the GLOBOCON database of 2018, GC is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide (Bray et al., 2018). It is estimated that each year over one million new cases of GC are diagnosed, and it is responsible for 1 in 12 of all the deaths related to cancer (Bray et al., 2018; Ferlay et al., 2018). Clinically, due to the late onset of symptoms, this disease is often diagnosed in the advanced stages thus limiting the available curative therapeutic options in >50% of the cases (Nobili et al., 2011).

In India, the GC incidence is very low as compared to the worldwide incidence, with an annual number of new cases being approximately 63,000 (Ferlay et al., 2013). GC in India shows a male predominance over females with a ratio of 2:1 (Ferlay et al., 2013) and the 5-year survival rate of patients with this cancer is nearly 18.7% (Allemani et al., 2015). Kashmir valley – a north Indian state, remains a high incidence area burdened with many commonly occurring cancers, particularly the cancers of the gastrointestinal tract (GIT) (Arshad and Siddiqi, 2012). GC is the most frequently encountered cancer among males and is the third most commonly reported cancer among females in Kashmir (Qurieshi et al., 2016). Kashmir valley is a mountain bound, distinct geographical area, which has been considered as an endemic cancer zone that presents a peculiar cancer profile (Rasool et al., 2012). This strikingly different pattern of cancer distribution is often attributed to the unique dietary practices followed by the Kashmiri population, predisposing them to a particular set of environmental and dietary carcinogens (Arshad and Siddiqi, 2012).

Although GC is the most prevalent cancer in the valley, only a few genetic studies have been carried out so far in relation to this cancer (Qurieshi et al., 2016). In the recent past, the association of only a few known genetic hot-spots implicated in gastric cancer elsewhere has been studied in the Kashmiri population (Slavin et al., 2019; Tan and Yeoh, 2015). Therefore, a dire need arises for identifying the role of other genetic factors in relation to this ethnic population of Kashmir Valley.

Section snippets

Classification of gastric cancer

Gastric adenocarcinoma is the most frequently encountered gastric tumor which accounts for >90% of the cases. Other rare types of GCs together account for <10% of the malignant lesion and include the mesenchymal tumors, primary gastric lymphomas, and carcinoid tumors (El-Rifai and Powell, 2002). Gastric adenocarcinomas are classified as cardia and non-cardia cancers based on their anatomical site. Cancers of the cardia occur in the region adjoining the Gastro-Esophageal junction (cardia),

Staging of gastric cancer

In the year 1987, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) introduced the cancer staging system. This staging is based on the local tumor depth of invasion (T), the presence and number of lymph node metastases (N), and the presence of distant metastases (M) (Hutter, 1987). The TNM (Tumor/Nodes/Metastases) staging remains the most widely accepted classification system for the staging of gastric cancer, detailed in Table 1.

Conclusion

GC a rapidly spreading highly aggressive disease is usually presented at the late stage for diagnosis and treatment. Our understanding of the molecular mechanisms of GC and its management is constantly progressing. Simultaneously, the identification of novel genetic markers promises to augment the development of personalized medicine and targeted therapies for patients who will benefit from specific treatment regimes. For the early detection of GC, the adoption of modern cancer screening

Compliance with ethical standards

The authors report no conflicts of interest. The authorship has been assigned only to the genuine contributors as per ICMJE guidelines. All the authors have read and approved the final manuscript.

Declaration of competing interest

The authors report no conflicts of interest.

Acknowledgment

The authors thank Mr. Aqib Magray, Centre of Research for Development, University of Kashmir for his valuable inputs during the preparation of the manuscript.

Source of funding

Bushra Nissar was financially supported by the Council of Scientific and Industrial Research New Delhi , India (file number: 09/251(0049)/2012-EMR-I) to carry out her research.

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