Age and Cancer: Insights into Tumor Genetics
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Chapter 1: Understanding Cancer and Age
Cancer remains the second leading cause of death globally, following heart disease, with approximately 1 in 5 individuals facing this challenge in their lifetime. The disease manifests when cells begin to multiply uncontrollably, disregarding the usual rules of growth and differentiation.
For a brief narrative on the life of a cancer cell, watch ‘Divide and Conquer’.
At its core, cancer arises from a series of genetic mutations. These mutations occur when errors arise during DNA replication in cell division. While not all mutations are harmful, a significant number can lead to cancer, especially as age increases the likelihood of these mutations accumulating. Aging correlates with a higher risk of cancer due to the greater number of mutations that can accumulate over time. Additionally, it’s important to note that changes in gene expression through epigenetic modifications also contribute to this risk.
Various external factors can also incite mutations. For instance, excessive ultraviolet (UV) exposure—whether from direct sunlight or tanning beds—strongly correlates with an increased risk of skin cancer. Other environmental influences, such as air pollution and processed meats, are associated with lung and colorectal cancers, respectively.
Moreover, our gut microbiome plays a significant role in cancer risk and may even enhance the efficacy of chemotherapy. Infections, such as with Helicobacter pylori, are also known to heighten the risk of stomach cancer.
Interestingly, our bodies may inadvertently assist cancer in its spread. Certain gene variants may promote cancer advancement, or substances found in aged blood could facilitate tumor metastasis.
Section 1.1: The Role of Age in Cancer Genetics
Despite the multitude of factors influencing cancer risk and development, age remains the primary risk factor for the majority of cancer types. While not universally applicable (consider the link between smoking and lung cancer or various pediatric cancers), age is a critical element in cancer susceptibility.
What about the genetic makeup of tumors? Are there differences between those found in older patients and their younger counterparts?
A recent study suggests there are indeed significant differences.
Researchers examined data from the Cancer Genome Atlas, a collaborative initiative by the National Cancer Institute and the National Genome Research Institute that gathers genomic information from over 20,000 tumor samples across 33 different cancer types. They analyzed genomic, transcriptomic (gene expression levels), and epigenetic changes in tumors from patients of varying ages.
Key findings reveal that tumors in older individuals exhibit a more unstable genome and are more prone to whole genome duplication, a factor often linked to poorer prognoses. Additionally, older tumors displayed a higher frequency of somatic copy-number alterations, where sections of the genome are duplicated. Notably, lung cancer appeared to deviate from this trend, but once smokers were excluded from the analysis, the trend reemerged.
These copy number alterations were frequently found in cancer-driver genes—genes that, when mutated, are implicated in cancer development. Tumor cells from older patients also contained a greater number of mutations, particularly where the DNA base cytosine (C) was replaced with thymine (T). However, exceptions emerged, such as in endometrial cancer, where younger patients had tumors with higher mutation rates, indicating distinct mutation patterns related to age.
These variations were also evident in the molecular signaling pathways involved in cancer progression across several cancer types, suggesting that both the initiation and progression of cancer can vary with age. The changes in gene expression associated with cancer also evolve over time, with some alterations influenced by DNA methylation.
The study's authors propose several factors that might drive these age-related shifts in cancer (epi)genetics, alluding to the overall physiological changes that occur as we age, including tissue modifications, atypical DNA methylation patterns, and fluctuations in hormone production.
While this study is exploratory in nature, it uncovers intriguing patterns that warrant further investigation. This research lays the groundwork for a better understanding of age-related differences in the molecular landscape of cancer, highlighting the crucial role that age plays in cancer genomic research, particularly with implications for clinical practice.
And perhaps, with this knowledge, we can discover ways to manipulate these patterns...
Chapter 2: The Impact of Genetics on Cancer Risk
Explore the various risk factors contributing to cancer and their implications.
Understanding the relationship between genetics and hereditary cancer risk.