The Prevalence and Implications of Viral Infections in Breast Cancer: A Comprehensive Analysis

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Breast cancer remains the most prevalent form of cancer globally and the leading cause of cancer-related deaths among women, according to the World Health Organization. In 2020, it was identified not only as the most common cancer worldwide but also the principal cause of female cancer deaths. In the Arab world, particularly in Jordan, breast cancer is notably prevalent and deadly, ranking among the top ten in incidence and mortality rates.

Etiology and Risk Factors

The etiology of breast cancer is understood to be multifactorial, involving a combination of genetic, environmental, and lifestyle factors. Age, smoking, alcohol consumption, and genetic predisposition are well-known risk factors. However, environmental factors, particularly viral infections, play a crucial role but are less understood and thus require further exploration.

Viral infections are hypothesized to infect breast epithelial cells and remain dormant, leading to what is termed “latent infection.” These infections contribute to cancer development through various mechanisms:

  • Viruses can inhibit apoptosis, allowing infected cells to avoid programmed cell death.
  • Viral DNA may integrate into oncogenic regions of the host cell’s DNA.
  • Activation of telomerase by viruses contributes to cellular immortality.
  • Induction of mitosis in fully differentiated cells can lead to uncontrollable cell division.
  • Interference with anti-oncogenic proteins and cell cycle regulators like p53 and RAS.

Viruses such as Epstein–Barr virus (EBV), human papilloma virus (HPV), and cytomegalovirus (CMV) have been linked to various cancers, including neuroblastoma, B cell lymphomas, cervical, and oropharyngeal cancers. The association between these viruses and breast cancer, however, remains a subject of active research and debate.


TABLE 1 – Etiology and Risk Factors of Breast Cancer: The Role of Viral Infections

Breast cancer is influenced by a combination of genetic, environmental, and lifestyle factors, but among the least understood are environmental factors such as viral infections. These infections may play a crucial role in the development of breast cancer through several mechanisms and are the focus of ongoing research.

Viral Infections and Breast Cancer

Viral infections can impact breast epithelial cells in several ways, leading to what is known as a “latent infection.” These viruses can inhibit apoptosis (the process of programmed cell death), integrate their DNA into critical regions of the host cell’s genome, activate telomerase (contributing to cellular immortality), induce uncontrollable cell division, and interfere with key cell cycle regulators like p53 and RAS.

The viruses most frequently implicated in cancer development include the Epstein-Barr virus (EBV), human papillomavirus (HPV), and cytomegalovirus (CMV). These viruses are known to be linked to several types of cancer such as neuroblastoma, B-cell lymphomas, and cervical and oropharyngeal cancers. The specific link between these viruses and breast cancer, however, remains a subject of active research and debate.

Mechanisms of Viral Oncogenesis

HPV is known for its role in cervical cancers, but its connection to breast cancer is still under investigation. HPV can integrate into the host cell’s DNA and use the cell’s machinery to replicate. This integration can disrupt normal cell functions by inactivating tumor suppressor proteins and may be involved in breast cancer development. Studies have found varying levels of HPV in breast cancer tissues, suggesting a possible link, although the data are not yet conclusive​ ​.

Similarly, EBV has been detected in breast cancer tissues, and while its role is not fully understood, it is known to infect mammary epithelial cells and might influence cancer through its effects on gene expression and oncogenic signaling pathways​​.

CMV’s presence in breast cancer is also noted, with detection rates varying significantly across different studies, which highlights the complexity of its potential role in oncogenesis​ ​.

Global Prevalence and Vaccination

The prevalence of HPV varies widely around the world, and vaccination rates are crucial in managing the spread of the virus. For instance, HPV vaccination is notably lower in Africa compared to other continents, which corresponds with higher infection rates​ ​. Vaccination against HPV is seen as a critical measure in preventing the types of cancers associated with the virus, including potentially breast cancer.

Concluding Remarks

The link between viral infections and breast cancer is a complex area of study with significant implications for prevention and treatment. While certain viruses are established as oncogenic in other cancers, their role in breast cancer continues to be explored. Understanding these relationships is vital for developing targeted interventions and improving outcomes for breast cancer patients globally.

Further detailed studies and broader epidemiological data are necessary to clarify the role of these viruses in breast cancer, which could potentially lead to new strategies for prevention and therapy. The ongoing research into viral etiologies of breast cancer holds promise but also calls for cautious interpretation until more definitive results are available.


Global Impact of Viral Infections on Cancer

Globally, chronic infections, both viral and bacterial, are implicated in approximately a fifth of all cancer cases, with a higher impact in developing countries where they account for about 20% of cancer-related deaths. Several regional studies have shown a correlation between viral infections and breast cancer incidence in countries like Iran, Pakistan, Syria, and Sudan, although some studies have contested these findings.

Focus on Jordan: A Case Study

In Jordan, the prevalence and impact of viral infections on breast cancer have been understudied. A pioneering study conducted recently aimed to investigate the presence of HPV, EBV, and CMV in breast cancer samples from a Jordanian female population. This study is significant as it represents the first focused investigation into these infections in the context of breast cancer in Jordan.

Study Findings and Discussion

The study found that HR-HPVs were detected in 24.5% of breast cancer samples, with none of the normal breast samples testing positive for HR-HPVs. This aligns with global data where HR-HPVs have been detected in varying percentages across different regions. Notably, HPV 16 was the most prevalent genotype found in the Jordanian breast cancer samples, consistent with findings from neighboring regions like Iraq and Egypt. However, the prevalence of HPV 18, commonly found in Iranian breast cancer patients, contrasts with the Jordanian data where HPV 16 dominates.

The detection rates for CMV in breast cancer samples were also significant, aligning with regional studies but showing considerable variation globally. In contrast, EBV was detected in about 16.4% of the Jordanian breast cancer cases, which is lower than the prevalence seen in some other parts of the MENA region and globally.

The study also explored the co-presence of these viruses in breast cancer samples, finding that a small percentage of cases had co-infections of HR-HPVs and EBV. These results suggest a potential cooperative role of these viral oncoproteins in the development of breast cancer, supporting the theory that viral infections could contribute to the pathogenesis of the disease through complex, multifactorial pathways.

Summary

This comprehensive analysis underscores the significance of understanding the role of viral infections in breast cancer, particularly in regions like Jordan where the disease is prevalent yet under-researched. The findings contribute to a growing body of evidence suggesting that chronic viral infections can play a role in the etiology of breast cancer, influencing its development and progression through a variety of molecular mechanisms. Further research is essential to fully elucidate these relationships, potentially leading to better prevention, diagnosis, and treatment strategies for breast cancer globally.


https://www.mdpi.com/1648-9144/60/5/699

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