Polymorphisms and Their Connection to Cancer
Polymorphisms, particularly single nucleotide polymorphisms (SNPs), are variations in the DNA sequence that occur commonly within a population. These genetic variations can influence the risk of developing cancer, the progression of the disease, and the response to treatment. This article reviews the indirect mechanisms by which polymorphisms can contribute to cancer and discusses common polymorphisms that have been linked to the disease.
Cancer is a complex disease characterized by uncontrolled cell growth and the ability of these cells to invade other parts of the body. While environmental factors play a significant role in the development of cancer, genetic predispositions are also critical. Polymorphisms, especially SNPs, are the most common type of genetic variation in humans and can affect gene expression and function, potentially leading to cancer.
Indirect Mechanisms of Polymorphisms in Cancer
Gene Expression and Function
Polymorphisms can influence the function of genes by altering their expression levels or the structure of their encoded proteins. SNPs within regulatory regions of a gene can affect the binding of transcription factors, thereby modulating gene expression. For example, polymorphisms in the promoter region of the TP53 gene, which encodes a tumor suppressor protein, can lead to altered levels of expression and contribute to cancer susceptibility (Petitjean et al., 2007).
Modulation of Signal Transduction Pathways
Signal transduction pathways regulate various cellular processes, including cell division, differentiation, and apoptosis. Polymorphisms that affect components of these pathways can indirectly contribute to carcinogenesis. For instance, SNPs in the PIK3CA gene, which is involved in the PI3K/AKT signaling pathway, have been associated with breast cancer (Samuels et al., 2004).
DNA Repair Mechanisms
DNA repair systems are crucial for maintaining genomic integrity. Polymorphisms in DNA repair genes can compromise the repair process, leading to an accumulation of DNA damage and an increased risk of cancer. A well-studied example is the polymorphism in the BRCA1 gene, which is linked to a higher risk of breast and ovarian cancers (King et al., 2003).
Metabolic Pathways
Polymorphisms can affect metabolic pathways that process carcinogens, drugs, and hormones, thereby influencing cancer risk. For example, SNPs in the CYP1A1 gene, which encodes a cytochrome P450 enzyme involved in the metabolism of polycyclic aromatic hydrocarbons, have been associated with lung cancer (Kiyohara et al., 1996).
Common Polymorphisms Associated with Cancer
Breast Cancer
The most well-known polymorphisms associated with breast cancer risk are in the BRCA1 and BRCA2 genes. These genes are involved in the repair of double-strand DNA breaks, and their mutations can lead to genomic instability and cancer (Antoniou et al., 2003).
Colorectal Cancer
Polymorphisms in the APC gene, which is a key regulator of the WNT signaling pathway, have been implicated in familial adenomatous polyposis, a condition that significantly increases the risk of colorectal cancer (Kinzler et al., 1991).
Lung Cancer
SNPs in genes involved in the metabolism of tobacco carcinogens, such as CYP1A1 and GSTM1, have been linked to an increased risk of lung cancer, particularly among smokers (Nakachi et al., 1993).
Prostate Cancer
Polymorphisms in the androgen receptor gene have been associated with the risk of prostate cancer. Variations in the number of CAG repeats in this gene can affect the activity of the androgen receptor and influence prostate cancer development (Giovannucci et al., 1997).
Takeaway
Polymorphisms play a significant role in cancer by affecting gene expression, protein function, and various biological pathways. Understanding these genetic variations is crucial for identifying individuals at higher risk of cancer, developing targeted therapies, and improving prognostic assessments. The first step to preventing cancer is having a DNA Coach test, report, and coach you on taking all the lifestyle and supplement protocols available.
References
Antoniou, A., Pharoah, P. D., Narod, S., Risch, H. A., Eyfjord, J. E., Hopper, J. L., & Easton, D. F. (2003). Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics, 72 (5), 1117–1130.
Giovannucci, E., Stampfer, M. J., Krithivas, K., Brown, M., Brufsky, A., Talcott, J., … & Kantoff, P. W. (1997). The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proceedings of the National Academy of Sciences, 94 (7), 3320–3323.
Kinzler, K. W., Nilbert, M. C., Su, L. K., Vogelstein, B., Bryan, T. M., Levy, D. B., & Hamilton, S. R. (1991). Identification of FAP locus genes from chromosome 5q21. Science, 253 (5020), 661–665.
Kiyohara, C., Yoshimasu, K., Takayama, K., & Nakanishi, Y. (1996). EPHX1 polymorphisms and the risk of lung cancer: A HuGE review. Epidemiology, 17 (1), 89–99.
Nakachi, K., Imai, K., Hayashi, S., & Kawajiri, K. (1993). Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Research, 53 (14), 2994–2999.
Petitjean, A., Achatz, M. I., Borresen-Dale, A. L., Hainaut, P., & Olivier, M. (2007). TP53 mutations in human cancers: Functional selection and impact on cancer prognosis and outcomes. Oncogene, 26 (15), 2157–2165.
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., … & Velculescu, V. E. (2004). High frequency of mutations of the PIK3CA gene in human cancers. Science, 304 (5670), 554.
