Anal Polyp
An anal polyp is an abnormal growth of tissue that protrudes from the lining of the anal canal or rectum. These growths are a type of colorectal polyp, varying in size, shape, and cellular composition. While many anal polyps are benign, some types can develop into more serious conditions, including colorectal cancer, over time.
Biological Basis
The development of polyps, including those found in the anal region, is a complex process influenced by both genetic and environmental factors. At a cellular level, polyp formation often involves dysregulated cell proliferation and abnormal tissue architecture. Genetic predispositions play a significant role, with studies exploring the heritability of various phenotypes, including different types of polyps. [1] Genome-wide association studies (GWAS) identify specific genetic variants that contribute to the risk of developing gastrointestinal conditions, including colon polyps . [2], [3], [4] Furthermore, inflammatory processes and immune responses are recognized contributors to the pathogenesis of gastrointestinal diseases, which can be linked to polyp formation. [3] Research also investigates specific types of polyps, such as serrated colorectal polyps, and their associated risk factors. [5]
Clinical Relevance
Anal polyps are clinically significant due to their potential to cause symptoms such as rectal bleeding, changes in bowel habits, or discomfort. They are frequently identified during routine physical examinations or endoscopic screenings. The primary clinical concern associated with anal polyps is their potential for malignant transformation, particularly for adenomatous polyps. Early detection, diagnosis, and removal of these growths are crucial preventive measures against colorectal cancer. Understanding the genetic architecture of digestive diseases, including polyp formation, helps in identifying individuals at higher risk, potentially guiding personalized screening strategies and earlier interventions . [1], [4]
Social Importance
The social importance of anal polyps lies in the broader context of colorectal health and cancer prevention. Public health initiatives aim to raise awareness about the importance of regular screenings, such as colonoscopies, for early detection and intervention. Addressing the societal stigma and discomfort often associated with discussing anal health issues is vital to encourage individuals to seek medical attention promptly, reducing delays in diagnosis and improving treatment outcomes. Advances in genetic research contribute to a more comprehensive understanding of risk factors, which can inform targeted public health campaigns and personalized patient care . [1], [4]
Methodological and Statistical Constraints
Research on complex traits such as colon polyps often faces challenges related to study design and statistical power. Many genome-wide association studies (GWAS) may utilize samples optimized for computational scalability rather than maximal statistical power, potentially limiting the detection of all relevant genetic associations. [6] Furthermore, the use of less stringent p-value thresholds in exploratory analyses, while expanding the scope of discovery, inherently increases the risk of including false positive associations, necessitating careful interpretation of such findings. [1] Replication of identified variants across diverse cohorts is crucial, and studies may sometimes lack sufficient effective sample sizes to reliably replicate lead variants, thereby impacting the robustness of findings. [7]
Ascertainment bias, particularly in hospital-based cohorts, is a significant methodological concern that can inflate correlation estimates between diseases or traits, potentially leading to spurious associations. [7] Rigorous quality control measures are essential to mitigate such inflationary effects in genetic data. [4] The choice of statistical methods and filtering criteria for genetic variants can also influence the power to detect associations and the overall calibration of results. [6]
Generalizability and Phenotypic Definition
A key limitation in understanding the genetic architecture of traits like colon polyps is the underrepresentation of non-European populations in genetic studies, which hinders the identification of population-specific rare variants and limits the generalizability of findings across diverse ancestries. [4] Genetic risk factors are often influenced by an individual’s ancestry, making trans-ethnic comparisons vital to understand shared and unique genetic contributions. [4] While efforts are made to group samples by ancestry and ethnicity to control for population stratification, the predominant focus on European cohorts in many analyses means that polygenic risk scores and genetic insights may not translate effectively to other populations. [6]
The definition and measurement of phenotypes can introduce variability and impact genetic analyses. Differences in diagnostic criteria, such as those based on ICD codes versus current clinical practice, or variations in phenotypic coding definitions across different biobanks, can lead to inconsistencies when combining or comparing data from multiple sources. [7] Additionally, constructing phenotype-phenotype networks from a single sample without external validation can result in spurious correlations between traits that are not genetically linked, affecting the interpretation of shared genetic architecture. [1]
Unaccounted Factors and Knowledge Gaps
The development of complex diseases such as colon polyps is not solely driven by genetic factors but involves an intricate interplay with environmental influences. [4] While studies may incorporate various covariates like age, sex, lifestyle factors, and socioeconomic status to account for some environmental effects [6] fully capturing and modeling complex gene-environment interactions remains a significant challenge. Shared environmental effects among close relatives can also confound genetic analyses if not adequately addressed. [6]
Despite advances in identifying genetic variants associated with complex traits, a substantial portion of heritability often remains unexplained by common genetic variants. This gap suggests that current genetic models may not fully capture the contributions of rare variants, structural variations, or complex epistatic interactions. Furthermore, methodological limitations, such as the inability of some advanced tools to capture correlations across traits, represent ongoing knowledge gaps that, if addressed, could significantly enhance our understanding of disease etiology and improve predictive models. [6]
Variants
The genetic landscape of gastrointestinal conditions, including anal polyps, involves a complex interplay of various genes and single-nucleotide polymorphisms (SNPs) that can influence cellular pathways critical for tissue homeostasis and growth. Among these, the PTBP2 and DPYD genes, along with specific variants like rs143703976, contribute to the broader genetic architecture underlying susceptibility to abnormal tissue growths. Genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) are instrumental in identifying these genetic associations across diverse populations, revealing significant loci that contribute to various traits, including those of the digestive system. [1] Such research highlights the polygenic nature of many common diseases and conditions, where multiple genetic factors, each with a small effect, collectively influence risk. [4]
The PTBP2 gene, also known as Polypyrimidine Tract Binding Protein 2, encodes an RNA-binding protein that plays a crucial role in post-transcriptional gene regulation, including alternative splicing, mRNA stability, and translation. Its function is particularly significant in cellular differentiation and development, processes that are often dysregulated in the formation of polyps and other abnormal tissue growths. Variants within PTBP2 could potentially alter the splicing patterns of numerous target genes, leading to the production of aberrant protein isoforms or changes in protein expression levels, which might contribute to uncontrolled cell proliferation or impaired apoptosis, characteristic features of polyp formation in the gastrointestinal tract. For instance, the broader category of gastrointestinal diseases, including colon polyp (CP) and gall bladder polyp, are phenotypes actively investigated in large-scale genetic analyses . [1], [3]
Similarly, the DPYD gene (Dihydropyrimidine Dehydrogenase) is central to pyrimidine metabolism, encoding the rate-limiting enzyme in the catabolism of uracil and thymine. This enzyme is vital for maintaining the balance of nucleotides within cells, which are the building blocks of DNA and RNA. Genetic variants in DPYD can lead to reduced enzyme activity, affecting nucleotide pools and potentially impacting DNA synthesis and repair mechanisms. Such metabolic imbalances can create an environment conducive to cellular errors and uncontrolled growth, thus contributing to the risk of developing various neoplastic conditions, including polyps in the digestive system. Understanding these genetic influences is critical for characterizing the shared genetic architecture between different gastrointestinal conditions and identifying potential therapeutic targets . [2], [3]
The specific genetic variant rs143703976 represents a particular alteration in the DNA sequence that may influence the function or expression of nearby genes, including PTBP2 or DPYD, or other genes within its regulatory domain. While its precise functional impact on anal polyp development requires detailed investigation, such variants can contribute to an individual's overall genetic predisposition by subtly altering gene activity or protein function. These small genetic changes, when combined with other genetic and environmental factors, can modify risk for complex traits like the formation of anal polyps. The identification of such variants through rigorous statistical analyses, often involving millions of genetic markers, helps to illuminate the intricate genetic basis of disease and health . [4], [6]
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs143703976 | PTBP2 - DPYD | anal polyp |
Signs and Symptoms
The provided research context does not contain specific information regarding the clinical presentation, typical signs, common symptoms, measurement approaches, variability patterns, or diagnostic significance of anal polyps. While "colon polyp" and "gall bladder polyp" are mentioned as phenotypes within genetic studies [3] no descriptive clinical details relevant to signs and symptoms are provided for any polyp type. Therefore, a detailed "Signs and Symptoms" section for anal polyps cannot be constructed based on the given sources.
Causes
The development of anal polyps is a multifactorial process influenced by a complex interplay of genetic predispositions, environmental exposures, and interactions between these elements. Understanding these causal pathways is crucial for comprehending their etiology.
Genetic Predisposition and Polygenicity
Anal polyps, like many complex traits, demonstrate a significant genetic component, with research highlighting shared genetic architectures across various gastrointestinal conditions and even some lung diseases. This suggests common underlying etiological mechanisms that contribute to polyp formation. [3] The occurrence of anal polyps is often polygenic, meaning multiple genes, each with a modest effect, collectively contribute to an individual's susceptibility. [1] Furthermore, pleiotropy, where a single genetic locus or gene influences multiple distinct phenotypes, is observed; for instance, a specific genetic region, 17q12-21.2, has been associated with both asthma and colon polyps, providing insights into broader gastrointestinal polyp formation. [3]
Beyond specific genetic regions, transcriptome-wide association studies (TWAS) and proteome-wide association studies (PWAS) have identified associations between variations in gene expression and protein levels with the risk of developing polyps. [3] These studies have revealed enrichments in biological processes related to immune and inflammatory responses, suggesting that genetic variants impacting these pathways are critical drivers in the pathogenesis of gastrointestinal polyps, including those found in the anal region. [3] Genetic effects can account for a substantial portion of the variance observed in such traits, underscoring the inherited component of risk. [6]
Environmental Influences and Lifestyle Factors
Environmental factors play a significant role in modulating the risk of anal polyp development. Lifestyle choices, including specific dietary patterns and other environmental exposures, are recognized as important risk factors for colorectal polyps, which encompasses anal polyps. [3] These external factors interact with an individual's inherent biological makeup to influence their susceptibility to polyp formation.
Beyond individual behaviors, broader shared environmental effects, such as those present within families or specific geographic localities, can also contribute to the overall incidence and prevalence of polyps. [6] Although the precise environmental triggers for anal polyps are not always fully elucidated, the collective impact of these external influences highlights the dynamic relationship between an individual and their surroundings in the complex etiology of polyp development.
Gene-Environment Interplay and Comorbidities
The formation of anal polyps is not solely a consequence of genetic inheritance or environmental exposure, but rather emerges from intricate gene-environment interactions. [3] In this interplay, an individual's genetic predisposition can be significantly modulated by specific environmental triggers, leading to varied disease outcomes. For example, a genetic susceptibility that increases inflammatory responses may only manifest as polyp development when combined with particular dietary habits or lifestyle factors. [1]
Moreover, the presence of comorbidities can contribute to the risk and understanding of anal polyps. Genetic correlations have been observed between colon polyps and other conditions, such as asthma, indicating shared etiological mechanisms or common pathways. [3] These cross-trait associations suggest that genetic variants influencing inflammatory processes or immune responses in one disease might also predispose an individual to the development of polyps within the gastrointestinal tract, highlighting the systemic nature of disease susceptibility.
Biological Background of Anal Polyps
Anal polyps, akin to other polyps found throughout the gastrointestinal tract, represent abnormal growths arising from the mucosal lining. Their formation and progression are complex processes influenced by a confluence of genetic predispositions, cellular dysregulation, and environmental factors. Research into digestive disorders, including colon polyps, provides significant insights into the underlying biological mechanisms that contribute to their development and potential for malignant transformation.
Pathophysiological Processes and Tissue-Level Changes
The development of anal polyps involves disruptions in normal tissue homeostasis within the anal and colorectal mucosa. These growths are characterized by an aberrant proliferation of epithelial cells, leading to the formation of a mass that protrudes into the lumen. Studies on early colorectal adenomas, a type of colon polyp, have identified conserved serum protein biomarkers associated with their growth, indicating specific molecular signatures during their initial stages. [8] The progression from a benign polyp to more advanced lesions, such as colorectal cancer, involves a series of cumulative genetic and epigenetic alterations that override normal cellular controls. Lifestyle factors have also been recognized as risk factors for serrated colorectal polyps, highlighting the role of gene-environment interactions in their etiology. [5] Various digestive tissue types, including the ColonSigmoid and ColonTransverse, are relevant in the context of polyp formation, suggesting that similar pathophysiological pathways may be active in anal polyps. [3]
Genetic Mechanisms and Regulatory Networks
The predisposition to anal polyps is significantly influenced by genetic factors, as evidenced by studies identifying shared genetic architecture across various digestive disorders, including colon polyps. Genome-wide association studies (GWAS) have pinpointed numerous single-nucleotide polymorphisms (SNPs) that are associated with these conditions. [3] Functional annotation and gene-mapping efforts link these SNPs to candidate genes, often located in or near crucial regulatory elements such as super-enhancers and promoters. Advanced techniques like three-dimensional (3D) chromatin looping are employed to map SNPs to distal target genes, revealing complex regulatory networks. [8] Furthermore, gene expression patterns across different digestive tissues are analyzed using expression quantitative trait loci (eQTL) mapping, providing insights into how genetic variants influence gene activity and contribute to polyp development. [8] Fine-mapping and colocalization analyses help to identify credible sets of causal variants within genetic regions, strengthening the evidence for their involvement in disease pathogenesis. [3]
Molecular and Cellular Pathways
At the molecular level, the formation of anal polyps is often driven by dysregulation of critical cellular signaling and metabolic pathways. Inflammatory responses and immune system processes are frequently implicated, with gene ontology (GO) terms such as "Regulation of inflammatory response," "Immune response," and "Immune effector process" being significantly enriched in analyses of related gastrointestinal diseases. [3] Specific biomolecules, including lymphotoxin, play a role in modulating the intestinal immune system and gut-associated lymphoid tissue (GALT) organs, which can influence local tissue environment and polyp formation. [8] Additionally, proteins like CCN1 have been shown to impact cellular processes, with its overexpression potentially attenuating bile-induced esophageal metaplasia by suppressing non-canonical NF-kappaB activation, a pathway often involved in inflammation and cell proliferation. [8] Ion channels like TRPC1 and ORAI1 have also been linked to colon cancer, suggesting their involvement in regulating cellular functions critical to polyp progression. [8] Proteome-wide association studies (PWAS) further identify critical proteins and their associations with gastrointestinal conditions, offering a comprehensive view of molecular alterations. [3]
Systemic Connections and Cross-Disorder Biology
The biology of anal polyps is not isolated but interconnected with other systemic conditions and disorders, particularly within the digestive system and beyond. Cross-disorder studies reveal shared genetic variants and causal relationships across numerous digestive disorders, highlighting common underlying etiological mechanisms. [8] For instance, a shared genetic architecture has been observed between lung and gastrointestinal diseases, suggesting broader systemic connections and pleiotropic effects of certain genetic loci. [3] This indicates that genetic predispositions or cellular pathways involved in one inflammatory or proliferative condition might also contribute to others, including anal polyps. Such insights into common pathways, including those related to inflammation, immune response, and cell activation, are crucial for understanding the complex nature of polyp development and its broader health implications. [3]
Genetic and Epigenetic Regulation of Cell Fate
The development of anal polyps is intricately linked to genetic and epigenetic regulatory mechanisms that govern cell proliferation and differentiation. Genetic variants, such as single-nucleotide polymorphisms (SNPs), play a crucial role by influencing gene expression through various regulatory elements. [8] These SNPs can act as expression quantitative trait loci (eQTLs), altering the levels of specific gene transcripts, or be situated within super-enhancers and promoters, regions critical for controlling transcriptional activity. [8] Furthermore, three-dimensional (3D) chromatin looping facilitates long-range interactions between distal regulatory elements and target genes, demonstrating a complex architectural influence on gene regulation relevant to polyp formation. [8]
Dysregulation of these genetic controls can lead to uncontrolled cell growth characteristic of polyps. For instance, genes like RUNX1T1, known for its function in cell fate determination, could contribute to aberrant cellular processes when its regulation is disturbed. [9] The cumulative effect of such genetic and epigenetic alterations can drive the initiation and progression of benign polyps towards more advanced stages, including colorectal adenomas. [8] Identifying these specific regulatory pathways provides insights into the fundamental molecular underpinnings of polyp development.
Inflammatory Signaling and Immune Dysregulation
Inflammatory signaling pathways and immune dysregulation are central to the pathogenesis of anal polyps. The non-canonical activation of the NFkappaB pathway, a key regulator of immune and inflammatory responses, has been implicated in conditions like esophageal metaplasia, which can precede polyp formation. [10] Conversely, overexpression of proteins like CCN1 can attenuate such NFkappaB activation, suggesting a regulatory feedback loop that, when disrupted, may promote pathological tissue changes. [10] The broader "cytokine-cytokine receptor interaction" pathway is notably enriched in gastrointestinal diseases, highlighting the critical role of intercellular communication via immune mediators in disease development. [3]
The immune system's involvement extends to the regulation of immune effector processes and leukocyte activation, which are fundamental to the inflammatory response observed in the gastrointestinal tract. [3] Genes such as LTA (Lymphotoxin alpha), a member of the tumor necrosis factor family, are master regulators of intestinal lymphoid development, and their dysregulation can significantly impact local immune homeostasis, contributing to inflammatory conditions and potentially polyp growth. [8] Similarly, the arachidonate 15-lipoxygenase (ALOX15) pathway, involved in lipid mediator production, demonstrates how specific inflammatory mediators can contribute to polyp formation, as a loss-of-function variant in ALOX15 has been shown to protect against polyp development in other tissues. [11] Activation of PPARγ signaling, for example, has been shown to attenuate colitis, suggesting its protective role against inflammation relevant to polyp formation. [12]
Metabolic Dysregulation and Oxidative Stress
Alterations in metabolic pathways and the induction of cellular stress are significant mechanisms contributing to anal polyp pathogenesis. Genes involved in fundamental processes like human energy metabolism, such as ATP6V1G2, have been identified as risk factors for conditions like colorectal cancer, often linked to the progression of polyps. [8] Dysregulation of ATP6V1G2 can lead to increased oxidative stress, a state of cellular imbalance that damages macromolecules and promotes chronic inflammation and uncontrolled cell growth, characteristic features of polyp development. [8]
Beyond general energy metabolism, specific lipid pathways, including cholesterol homeostasis, are also implicated. For example, the genes ABCG5 and ABCG8 play crucial roles in cholesterol secretion, and mutations in these genes can lead to sterol accumulation. [8] This accumulation can contribute to cellular dysfunction and inflammation within the intestinal lining, potentially fostering an environment conducive to polyp formation and growth. [8] Metabolic reprogramming, therefore, provides a fertile ground for the aberrant cellular behavior seen in polyps.
Inter-Pathway Crosstalk and Disease Progression
The development of anal polyps and their progression to more severe diseases involves complex systems-level integration and extensive pathway crosstalk. Studies reveal a shared genetic architecture and causal relationships among various digestive disorders, indicating that dysregulation in one pathway can have ripple effects across a network of interconnected biological processes [8]
This intricate network extends to specific cellular components, such as TRPC1 and ORAI1 channels, which are calcium channels implicated in colon cancer and play roles in cell signaling and proliferation, thus contributing to polyp progression. [13] Furthermore, proteins like Inter-alpha-trypsin inhibitor heavy chain 4, which is associated with growing early colorectal adenomas, exemplify how specific molecular players, when dysregulated, can integrate into these broader disease networks, driving the emergent properties of polyp formation and malignant transformation. [14] Understanding these integrated pathways is crucial for identifying comprehensive therapeutic targets.
Frequently Asked Questions About Anal Polyp
These questions address the most important and specific aspects of anal polyp based on current genetic research.
1. My dad had anal polyps. Does that mean I'm definitely going to get them too?
Not necessarily "definitely," but your risk is higher. Genetic predispositions play a significant role, and traits like polyp formation can run in families. However, environmental factors and lifestyle choices also influence whether you develop them. Regular screenings are especially important for you.
2. I eat pretty healthy. Does that protect me from getting polyps?
Eating healthy is great for overall health, but it doesn't guarantee complete protection. While lifestyle factors are important, your genetic makeup also significantly influences your risk. Some individuals may have a genetic predisposition that makes them more susceptible, even with a healthy diet.
3. If I'm feeling fine, do I really need to get screened for anal polyps?
Yes, you absolutely should. Many polyps don't cause symptoms initially, but they can still be a precursor to cancer. Understanding your genetic risk factors, even if you feel healthy, can help your doctor recommend personalized screening strategies.
4. I'm not of European descent. Does my ethnic background change my polyp risk?
Yes, your ancestry can influence your genetic risk. Most genetic studies have focused on European populations, so specific risk factors for other ethnic groups are less understood. It's important for research to include diverse populations to understand how genetic contributions vary across different ancestries.
5. Can stress or inflammation in my gut make me more likely to get anal polyps?
Yes, research suggests a connection. Inflammatory processes and immune responses are known contributors to various gastrointestinal diseases, which can be linked to polyp formation. While genetics play a role in inflammation susceptibility, environmental factors like stress can also contribute.
6. Why do some healthy people get polyps while others who eat poorly never do?
This often comes down to individual genetic predispositions. While lifestyle matters, some people inherit genetic variants that increase their risk of polyp formation, regardless of their healthy habits. Conversely, others might have protective genetic factors that make them less susceptible even with less ideal lifestyles.
7. Would a special DNA test tell me if I'm at high risk for anal polyps?
Potentially, yes. Genetic research, including genome-wide association studies (GWAS), identifies specific genetic variants that contribute to the risk of conditions like colon polyps. These insights can help identify individuals at higher risk, potentially guiding personalized screening strategies.
8. If I have anal polyps, should my children get checked earlier than others?
It's a good idea to discuss this with your doctor. Given that genetic predispositions play a significant role in polyp development and polyps can run in families, your children might benefit from earlier or more frequent screenings. This helps in early detection and prevention.
9. Does getting older automatically mean I'm more likely to get polyps?
While age is a known risk factor, it's not "automatic" and it interacts with genetics. Your genetic predisposition can influence how much your risk increases with age. Regular screenings become even more critical as you get older, especially if you have other risk factors.
10. Can exercise really help reduce my risk of getting polyps, even with a family history?
Yes, exercise and a healthy lifestyle can help, even if you have a family history. While genetic factors contribute significantly to risk, they don't determine everything. Environmental and lifestyle factors interact with your genes, and positive habits can help mitigate some of that inherited risk.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
[1] Choe EK, et al. "Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits." Scientific Reports, vol. 12, no. 1, 2022, p. 1930.
[2] Walters RG, et al. "Genotyping and population characteristics of the China Kadoorie Biobank." Cell Genomics, vol. 3, no. 8, 2023.
[3] You D, et al. "A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases." Nature Communications, vol. 16, no. 1, 2025, p. 3032.
[4] Liu TY, et al. "Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population." Science Advances, vol. 10, no. 20, 2024.
[5] Bailie, L. et al. "Lifestyle risk factors for serrated colorectal polyps: A systematic review and meta-analysis." Gastroenterology, vol. 152, 2017, pp. 92–104.
[6] Loya H, et al. "A scalable variational inference approach for increased mixed-model association power." Nature Genetics, vol. 56, no. 5, 2024, pp. 886-897.
[7] Saarentaus, E. C., et al. "Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation." Nature Communications, vol. 14, no. 1, 2023, p. 293. PMID: 36653354.
[8] Jiang, Y., et al. "A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders." iScience, 2023.
[9] Hu, N., et al. "RUNX1T1 function in cell fate." Stem Cell Res. Ther., vol. 13, 2022, p. 369.
[10] Dang, T., et al. "Overexpression of CCN1 in Het1A cells attenuates bile-induced esophageal metaplasia through suppressing non-canonical NFkappaB activation." Cytokine, vol. 116, 2019, pp. 61–69.
[11] Kristjansson, R.P., et al. "A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis." Nat Genet, vol. 51, no. 2, 2019, pp. 267-276.
[12] Li, D., et al. "Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPARγ signaling activation." Microbiome, vol. 9, 2021, p. 83.
[13] Villalobos, C., et al. "TRPC1 and ORAI1 channels in colon cancer." Cell Calcium, vol. 81, 2019, pp. 59–66.
[14] Ivancic, M.M., et al. "Conserved serum protein biomarkers associated with growing early colorectal adenomas." Journal of Proteome Research, vol. 116, 2019, pp. 8471–8480.