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Part 2: H. pylori and its Association with Gastric Cancer in Depth

Helicobacter pylori, also known as H. pylori, is a bacterial species that thrives in the stomach lining of humans. H. pylori is estimated to be present in 60% of adults, making it significantly more prevalent than other forms of bacteria.(1 ) Most infections involving H. pylori are benign and do not lead to illness; however, the presence of one of these infections is associated with a higher risk for various gastric complications and, in some cases, can lead to progressive illness.(2) When present, the most common symptoms of an H. pylori infection are stomach and small intestine ulcers, issues which are highly treatable with today’s medicine. An H. pylori infection can lead to other conditions, however, that are less common but much more severe. A simple infection can progress into several diseases and conditions, including gastritis and, in the most severe cases, gastric cancer.(1)

Stomach cells' inflammatory response to sustained H. pylori infections can lead to cancer as H. pylori affects the makeup of protein complexes in stomach cells.


In the United States, stomach cancer is less prolific than other forms of cancer, with estimates projecting around 27,000 new cases each year and about 11,000 deaths.(3) Globally, stomach cancer is a much more impactful issue. Of the twenty countries where stomach cancer is most prevalent, over half are considered underdeveloped. Incidence rates in these countries can reach as high as 41.8 cases per 100,000 people.(4) Additionally, compared to other cancer types like bone cancer and leukemia, stomach cancer is generally diagnosed later in life. The aforementioned stomach cancer from H. pylori infections, however, can develop before twenty years.(5) H. pylori infection is the leading cause of stomach cancer worldwide. A major reason for this is because H. pylori infections usually occur during childhood and do not present symptoms, a phenomenon that makes  the bacteria very hard to detect before it becomes carcinogenic.(1),(6)


Uniquely, studies have shown that diet is a key lifestyle factor correlated with H. pylori infection.(6) Considering H. pylori converts nitrates and nitrites into carcinogenic compounds, individuals  who consume significant amounts of pickled vegetables and cured meats are at a particularly higher risk.(6) In order to reduce the overall public health threat posed by this bacteria, H. pylori and the mechanism through which it operates in the human body need to be further investigated through novel research. Scientific innovation in this sector possesses the potential to eradicate a major risk factor of stomach cancer. 


To take a closer look at the biomolecular mechanisms that underlie these types of infections, Zhang et al. recently conducted a research study that analyzed the role of long non-coding RNA H19 (lncRNA H19) and its interaction with H. pylori in the development of stomach cancer.(7) Long non-coding RNAs are highly transcribed and translated during cell development. LncRNA H19 is typically found at high levels in cancer cells, and it plays a role in rapid cell proliferation and invasion, two traits that characterize cancer development.(8) Additionally, change in expression of the H19 RNA can cause rapid cell proliferation, which can in turn lead to abnormal, carcinogenic cell development.(9)


The researchers quantitatively measured lncRNA in blood from stomach cancer tissue and subsequently assessed and quantified cancer cell reproduction, movement, and infection habits with a series of assays. One of their findings was that stomach cancer cells infected with H. pylori showed higher levels of lncRNA H19 expression, meaning that the H. pylori infection could play an important role in the cell development issues that lead to some types of stomach cancer. Additionally, they concluded that H. pylori promoted the survival and proliferation of stomach cancer cells and that it accomplishes this by affecting the function of the NF-κB protein complex, which plays multiple important roles in healthy cell survival, proliferation, and immunity.(7)


A hindered or altered NF-κB complex could thus help facilitate the development of cancer cells when H. pylori is present. Potential future research directions could investigate how to suppress elevated lncRNA H19 expression or how to increase the resilience of the NF-κB protein. The rate of gastric cancer diagnosis is small, and one correct research direction could provide a great deal of insight into how stomach cancer arises from H. pylori infection!


With your help, we can provide funding to support crucially needed research pertaining to infection-induced cancers like those of H. pylori! Let's make a difference together.


- Noah, RGHGF Staff


Want to learn more? Check out our references below!

References:

(1) Colledge, Helen, and Jacquelyn Cafasso. “H. Pylori Infection.” Healthline, 26 Oct. 2017, www.healthline.com/health/helicobacter-pylori#causes.


(2) Cover, Timothy L, and Martin J Blaser. “Helicobacter pylori in health and disease.” Gastroenterology vol. 136,6 (2009): 1863-73. doi:10.1053/j.gastro.2009.01.073


(3) Siegel, Rebecca L., et al. “Cancer Statistics, 2020.” CA: A Cancer Journal for Clinicians, vol. 70, no. 1, 2020, pp. 7–30., doi:10.3322/caac.21590.


(4) Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. https://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/stomach-cancer-statistics%20%20


(5) “Risk Factors: Age.” National Cancer Institute, www.cancer.gov/about-cancer/causes-prevention/risk/age


(6) “Key Statistics About Stomach Cancer.” American Cancer Society, 9 Jan. 2019, www.cancer.org/cancer/stomach-cancer/about/key-statistics.html.


(7) Zhang, Y., Yan, J., Li, C. et al. J Inflamm (2019) 16: 23. https://doi.org/10.1186/s12950-019-0226-y


(8) Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4):a000034. doi:10.1101/cshperspect.a000034 https://pubmed.ncbi.nlm.nih.gov/20066092/


(9) Lecerf, C., Le Bourhis, X. & Adriaenssens, E. The long non-coding RNA H19: an active player with multiple facets to sustain the hallmarks of cancer. Cell. Mol. Life Sci. 76, 4673–4687 (2019) doi:10.1007/s00018-019-03240-z



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