• info@icbcongress.com
• English
• Persian

• Login

Create Free Account

INTERNATIONAL CONGRESS OF

CancerGenetics

• Genetic Influences on Pregnancy Maintenance and Cancer Risks

• Fatemeh Sadat Kohandani,¹ Mehrdad Hashemi,^2,* Kimia Sadat Esfahani,³
  1. 1- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  2. 1- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran.
  3. 1- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  
  
  
• Introduction: Cancer can develop in conjunction with various conditions and physiological states, such as obesity, aging, and pregnancy. The incidence of cancer during pregnancy is approximately 1 in 1,000 to 2,000 pregnancies, with the most common types being breast cancer, melanoma, cervical cancer, lymphoma, and acute leukemia. Cancer during pregnancy is typically defined as a diagnosis made either during the pregnancy or within one year post-delivery. As the trend of delaying pregnancy continues, the incidence of cancer associated with pregnancy is on the rise. Telomerase activity, which is usually minimal in normal somatic cells, is significantly elevated in 85% of human cancers. The intracellular levels of telomerase are strongly correlated with a cell's proliferative potential. During human pregnancy, telomerase activity peaks in the first trimester and gradually decreases as the placenta matures. Additionally, survivin—a protein known to promote cell proliferation and inhibit apoptosis—is overexpressed in various cancers and is similarly upregulated by trophoblast cells during pregnancy. Also HLA molecules regulate the immune system by presenting peptides that allow immune cells to distinguish between healthy and abnormal cells. While the immune system relies on HLA for recovery, it can also promote immune tolerance, increasing disease susceptibility or supporting fetal survival during pregnancy. Both cancer and pregnancy share mechanisms of immune tolerance, involving irregular peptides and abnormal HLA expression. Early fetal development and tumor growth are similar in their ability to evade immune detection. Understanding these parallels could lead to new treatments for pregnancy complications and cancer by targeting shared pathways. The purpose of this review is to investigate genetic influences on pregnancy retention and cancer risks.
• Methods: Twenty relevant articles investigating the relationship between genetic influences on pregnancy retention and cancer risks were identified through searches of PubMed and Google Scholar databases using predefined keywords. These articles were then selected for review and analysis.
• Results: The early development of a fetus in the first trimester shares similarities with the growth of tumor cells. Both entities possess genetic differences from the host, which should trigger recognition by the immune system. However, each employs mechanisms to create a tolerogenic immune environment, allowing for survival. ERAP1 and ERAP2 trim peptides for antigen presentation on HLA class I molecules in the endoplasmic reticulum, a key process for tumor cell-immune system interactions. These proteins are potential anti-cancer targets, enhancing immune responses through T and NK cell-mediated cytotoxicity. Abnormal HLA peptides linked to ERAP2 expression are found in both pregnancy and cancer. ERAP enzymes and HLA class I peptides also contribute to genetic risk for Hodgkin’s Lymphoma, with significant interactions observed between HLA-A11 and ERAP1 SNP rs27038, as well as ERAP1 SNP rs26618 and HLA-Cw2. Risk alleles can further influence ERAP expression. Trophoblast cells secrete various immunomodulatory proteins, including soluble HLA-G, which disrupts NK/DC interactions, promotes proinflammatory cytokine release, and induces CD8+ cell apoptosis. Soluble HLA-G is commonly observed in cancers such as leukemia, multiple myeloma, breast and ovarian carcinoma, and lung cancer. Cancer cells also induce monocytes to release HLA-G, further suppressing antitumor immunity. Tumors diagnosed during pregnancy show high levels of RANKL, indicating pregnancy’s influence on breast tumor biology. Genomic analysis reveals similar common mutations (e.g., TP53, PIK3CA) between pregnant and non-pregnant breast cancer patients, but pregnant patients display a higher frequency of non-silent mutations, mucin gene mutations, and mismatch repair deficiency signatures. Trophoblast and tumor cells share invasion-related proteins. Heat shock protein 27 (HSP27) is elevated in both, promoting metastasis and inhibiting apoptosis. Matrix metalloproteinases (MMPs) aid in neovascularization and tissue remodeling, while Ras homolog family member A (RhoA) and its signaling pathway regulate migration and proliferation. Galectin-1 contributes to tumor and trophoblast invasion, immune regulation, and angiogenesis.
• Conclusion: Current research on the immune effects of pregnancy and cancer remains incomplete, warranting further investigation into how these conditions impact the immune environment. A deeper understanding of these immune interactions in the context of pregnancy disorders and cancer could pave the way for novel therapeutic approaches for both conditions. Identifying key factors in pregnancy maintenance and their association with cancer incidence could pave the way for preventive measures against cancer and the development of personalized, targeted treatments for women.
• Keywords: Cancer, Genetics, Fetus, Pregnancy