Family history and hereditary traits are among the most common cancer risk factors. From the American Cancer Society to the National Cancer Institute, leading sources suggest that if your biological parents or someone closely related to you develops a particular type of cancer, you might also be at risk.
Genetics can play a significant role in cancer occurrence. But how so? Let’s explore the science behind cancer and genetics, as well as identify the specific genes associated with certain cancer types.
Understanding Cancer and Genetics
A person’s genetic makeup is determined by the genes inherited from their biological parents. The sperm and egg cells combine to produce 46 chromosomes. Chromosomes contain genetic information that provides instructions for how cells in the body operate. Genetic mutations in our chromosomes can contribute to cancer development by disrupting the normal functioning of cells and altering the instructions they receive. However, not all genetic mutations lead to cancer, and cancer can also emerge without any significant genetic changes.
If the event that a genetic mutation occurs, the following are the root causes of such changes:
- Germ-line mutation: a change in the gene inherited from the parents
- Somatic mutation: a change in the gene due to external factors such as oxidative stress, diet, and carcinogens like tobacco smoke, acrylamide, and cadmium
In addition, according to a 2001 oncological article, Hanahan and Weinberg, authors of the study Hallmarks of Cancer: The Next Generation, identified six hallmark features or “defects in commands” of the cancer cell phenotype:
- Cells disregard signals to cease proliferation
- Cells disregard signals to differentiate
- Cells lose the capacity to sustain proliferation
- Cells avoid their programmed death or apoptosis
- Cells invade its surrounding tissues
- Cells form new blood vessels to support their own growth or angiogenesis
These phenomena occur due to mutations in human genetics referred to as (1) oncogenes and (2) tumor-suppressing genes. Oncogenes are dominant by nature, as a single copy of the cancer-critical gene carrying a gain-of-function mutation can promote the development of cancer within a cell. On the other hand, defects in tumor-suppressing genes can cause loss-of-function effects, allowing cancer cells to multiply uncontrollably.
Molecular Genetics of Prominent Cancer Types
The Human Genome Project is one of the most remarkable feats in the study of genetics. The objective of this international scientific research initiative was to determine the base pairs constituting human DNA, and to identify, map, and sequence all the genes in the human genome, considering both their physical and functional attributes. Developments in genetic engineering also provided the scientific community with a deeper understanding of genetics at the molecular level, giving more insight into the link between cancer and genetics.
Applying the breakthroughs of the Human Genome Project and genetic engineering, below, we will discuss the most common cancers in the United States and the genes that drive them to develop.
Common Cancers and Genetic Links
We will use cancer data from the Surveillance, Epidemiology, and End Results (SEER) program to report the numbers. Information on the risk factors for each type of cancer discussed will come from the National Cancer Institute.
Following skin cancer, malignancies in the breast are the most common among women in the United States. Risk factors for this disease include old age, dense breast tissue, and a personal or family history of breast cancer.
Cancer cells in the breast involve somatic and germ-line mutations. Somatic changes in breast tumors include mutation, amplification, and deletion of the genes, while germ-line mutations include the BRCA1 and the BRCA2 genes.
Oncogenes amplification can promote cancer cell proliferation. Amplified oncogenes (MYC, ERBB2, and CCND1) are present in a diverse range of solid tumors and represent a significant genomic force driving the progression of these tumors. Cancer cells may also grow and multiply due to mutations in tumor-suppressing genes. In breast cancer, these genes include ATM, CDH, and TP53.
Mutations in the BRCA1 and the BRCA2 genes can raise the incidence of somatic deletion and amplification in breast cancer. Gene carriers of BRCA1 also have a heightened risk of mutations in the TP53 gene.
Add Genetics of Breast Cancer to your reading list for a complete guide to breast cancer genes.
Approximately 1 in 9 men aged 65 and over can develop prostate cancer. It comprises 14% of all new cancer incidences in the United States. Aside from old age and genetics, risk factors for this disease include hormonal problems.
A summary of the genes possibly related to prostate cancer is detailed in this study published in 2000. The researchers classified the genes into three categories:
- Normal prostate development: androgen receptor and NKX3.1
- Initiation and progression to carcinoma: deletion or mutation of NKX3.1
- Advanced carcinoma metastasis: Amplification or mutation of androgen receptor
Both androgen receptor and NKX3.1 genes play critical roles in regulating prostate development. In particular, the androgen receptor gene is necessary for the initial formation of the prostate buds, and the NKX3.1 gene is involved in both the formation of prostate buds and the production of secretory proteins – an independent prognostic/diagnostic marker for prostate cancers.
Lung cancer has the highest mortality rate among all cancer types. In 2022, SEER estimated 130,108 deaths from lung carcinoma. Due to its prevalence and high death rate, it’s important to familiarize ourselves with lung cancer’s many risk factors, including tobacco smoke and radon exposure. Lung cancer risk also increases due to HIV infection and family history.
Two significant genetic factors that contribute to the development of lung malignancies are the oncogene RAS and the tumor-suppressor gene RB. Mutations in these genes can lead to a loss of control over cell growth and division, which can result in apoptosis evasion and senescence, angiogenesis, tissue invasion, and metastasis. Furthermore, external factors such as cigarette smoke can cause changes in the genetic code through DNA methylation, leading to an increased risk of cancer.
Colorectal cancer is both prevalent and deadly. SEER revealed that cancer affecting the colon or rectum has the fourth-highest number of predicted incidences and the second-highest number of expected deaths. Aside from age and family history, risk factors include cigarette smoking, excessive alcohol consumption, and obesity.
The most significant oncogenes and tumor-suppressor genes in colorectal cancer are APC, KRAS, and 53. When mutations occur in these genes, they can lead to DNA methylation and changes in chromatin structure within cells. As a result, this can cause alterations in cellular metabolism, proliferation, differentiation, and survival, contributing to the occurrence and progression of colorectal cancer.
Ongoing research on epigenetics in colorectal cancer is necessary due to the strong link between this region of the body and an individual’s diet. By studying epigenetics, we can gain insight into how external factors can influence colorectal cancer occurrence.
The Path Toward Beating Cancer Despite Genetic Predisposition
If you or a loved one are facing a cancer diagnosis, it’s crucial to seek medical treatment from a qualified center. Alternative cancer treatment options may vary depending on the type and stage of cancer, and early intervention can improve outcomes. Contact us today to discuss the best course of action and create a personalized treatment plan.