Benign Digestive System Neoplasm

Benign digestive system neoplasms are non-cancerous growths that originate in the tissues of the gastrointestinal tract, which includes organs from the esophagus to the anus. Unlike malignant (cancerous) tumors, benign neoplasms do not spread to other parts of the body (metastasize) and typically do not invade surrounding tissues. While they are not life-threatening in the same way as cancer, their presence can still cause a range of symptoms and may, in some cases, have the potential to transform into malignant forms over time.

The biological basis for the development of benign digestive system neoplasms involves complex interactions between genetic predisposition and environmental factors. These growths arise from uncontrolled cell proliferation, often driven by accumulated genetic mutations or epigenetic changes in cells that line the digestive tract. These alterations can affect genes responsible for regulating cell growth, division, and programmed cell death, leading to the formation of a localized mass of abnormal cells. Research into other benign conditions, such as benign prostatic hyperplasia (BPH), has identified specific genetic variants associated with inherited susceptibility, highlighting the role of an individual’s genetic makeup in the risk of developing benign tumors ^[1].

Clinically, benign digestive system neoplasms are significant due to their potential to cause symptoms, their need for monitoring, and the risk of malignant transformation. Depending on their size and location, these neoplasms can lead to symptoms such as abdominal pain, bleeding, obstruction, or difficulty swallowing. Many benign digestive polyps, particularly adenomas found during colonoscopies, are considered precancerous lesions because they have the potential to evolve into colorectal cancer if not removed. Therefore, early detection through screening programs and timely intervention are crucial for preventing more serious health outcomes. Diagnosis typically involves endoscopic procedures, imaging studies, and biopsy for histological examination.

The social importance of benign digestive system neoplasms is considerable, impacting public health and individual well-being. Their high prevalence, particularly of conditions like colon polyps, necessitates widespread screening initiatives, which are vital for reducing the incidence and mortality of associated cancers. The management of these conditions also places a significant demand on healthcare resources. Furthermore, the psychological impact on individuals undergoing surveillance and repeat procedures, and the need for lifestyle adjustments, underscore their broader societal relevance. Continued research into the genetic underpinnings and risk factors aims to improve early detection, personalize risk assessments, and refine preventive strategies.

Limitations

Understanding the genetic underpinnings of benign digestive system neoplasms presents several inherent challenges, which can impact the interpretation and generalizability of research findings. These limitations span methodological and statistical aspects, population specificity, and the comprehensive identification of all contributing factors.

Methodological and Statistical Challenges

The statistical power of studies on benign digestive system neoplasms can be limited by sample sizes, a challenge exemplified by investigations into related conditions such as benign prostatic hyperplasia, where some analyses involved as few as 498 cases and 1,684 controls ^[2]. Such modest cohort sizes may restrict the ability to detect genetic variants with small effect sizes, potentially leading to an overestimation of the magnitude of association for initially identified loci. Furthermore, the selection of control groups, such as the exclusion of “generic” controls in some genome-wide association studies, could introduce biases that affect the broader applicability of the findings ^[3].

Challenges in replicating genetic associations across different studies are also evident, with some findings, even related to fundamental processes like DNA repair, showing inconsistency ^[3]. This highlights the need for robust replication efforts and emphasizes that initial associations require further validation. The reliance on meta-analyses, which combine data from multiple genome-wide association studies to increase statistical power and confirm susceptibility loci for various conditions, underscores the inherent limitations of individual studies in establishing definitive genetic links ^[4].

Population Specificity and Phenotypic Definition

A significant limitation in understanding the genetic architecture of benign neoplasms stems from the population-specific nature of many genetic studies. For instance, research into related conditions like nasopharyngeal carcinoma has predominantly focused on individuals of Chinese ancestry, identifying specific genetic determinants within this population ^[5]. While these findings are crucial for the studied groups, they raise questions about the generalizability of identified susceptibility loci to diverse global populations, potentially limiting the comprehensive understanding of genetic risk across different ancestral backgrounds.

The precise definition and characterization of benign digestive system neoplasms also present inherent challenges. While studies on conditions like benign prostatic hyperplasia meticulously define phenotypes such as lower urinary tract symptoms, the broad spectrum of “benign digestive system neoplasm” could encompass a heterogeneous group of conditions^[2]. Variations in diagnostic criteria, classification systems, and disease progression across different studies or clinical settings could introduce phenotypic heterogeneity, which might obscure true genetic associations or lead to inconsistent findings.

Unaccounted Factors and Mechanistic Gaps

The current understanding of benign digestive system neoplasms may be incomplete due to the potential influence of unmeasured environmental or gene-environment interactions. While genetic variants are identified, the interplay between these genetic predispositions and lifestyle, dietary, or other environmental exposures is often not fully elucidated in genetic research. This gap means that a significant portion of the variability in susceptibility, often referred to as missing heritability, may remain unexplained by genetic factors alone, necessitating a more integrated approach to risk assessment.

Furthermore, significant knowledge gaps persist regarding the functional mechanisms through which identified genetic variants contribute to the development of benign neoplasms. For example, many of the statistically significant single nucleotide polymorphisms (SNPs) identified in genetic studies are located in intergenic regions^[2]. The precise biological role of these non-coding variants, how they impact gene expression or cellular pathways, and their direct contribution to disease etiology often remain unclear, presenting a challenge for translating genetic associations into a deeper mechanistic understanding of the disease.

Variants

ARHGAP24 (Rho GTPase Activating Protein 24) plays a crucial role in regulating cellular processes by controlling the activity of Rho GTPases, which are key molecular switches governing the actin cytoskeleton. These GTPases influence cell polarity, adhesion, migration, and proliferation—all fundamental aspects of tissue development and homeostasis. The variant rs137954472 , likely located in a non-coding region, could potentially alter the expression levels or functional efficiency of ARHGAP24. If ARHGAP24’s activity is diminished by this variant, it could lead to overactive Rho GTPase signaling, promoting uncontrolled cell growth and migration, which are cellular behaviors often observed in the development of benign digestive system neoplasms, such as polyps or adenomas ^[4].

LPIN1 (Lipin 1) is a multifaceted protein involved in both lipid metabolism and gene regulation, acting as a phosphatidate phosphatase crucial for triglyceride synthesis and as a transcriptional coactivator for nuclear receptors. This dual role positions LPIN1 at the intersection of energy homeostasis and cellular signaling pathways. The variantrs7599768 , likely a non-coding polymorphism, may affect LPIN1’s expression or its ability to regulate lipid synthesis or gene transcription. Alterations in LPIN1 function can lead to dysregulated lipid profiles and cellular metabolic imbalances, which are increasingly recognized as contributors to various disease states, including cancer development^[6]. The impact of such a variant could influence how cells in the digestive tract manage their energy resources, thereby affecting their growth characteristics.

Key Variants

RS ID	Gene	Related Traits
rs137954472	RN7SKP48 - ARHGAP24	benign digestive system neoplasm
rs7599768	LPIN1	benign digestive system neoplasm

Signs and Symptoms

Initial Presentation and Symptomatology

Diagnostic Evaluation and Characterization

Phenotypic Diversity and Clinical Implications

The causes of benign digestive system neoplasms are multifaceted, encompassing a complex interplay of genetic predispositions, environmental exposures, and physiological changes over time. Understanding these factors is crucial for elucidating the mechanisms behind abnormal, non-malignant cell proliferation within the digestive tract.

Genetic Predisposition and Polygenic Risk

Many benign digestive system neoplasms exhibit a significant genetic component, where inherited variants contribute to an individual’s susceptibility. Genome-wide association studies (GWAS) have identified numerous common susceptibility polymorphisms that collectively increase risk, indicating a polygenic nature for various related conditions. For instance, meta-analyses have pinpointed common variants near genes such as SH2B3 and TSHZ1 as susceptibility loci for colorectal cancer, a condition affecting the digestive system, suggesting similar underlying genetic mechanisms could influence benign growths in these tissues^[7]. These genetic variations may alter cellular pathways involved in growth regulation, immune response, or tissue repair, thereby increasing the likelihood of abnormal, non-malignant cellular proliferation.

Specific genetic regions, such as the HLA class I antigen recognition groove on chromosome 6p21.3, have been identified as principal genetic determinants for certain related conditions, like nasopharyngeal carcinoma, highlighting the role of immune-related genes in disease susceptibility^[5]. Furthermore, novel loci within genes like CLPTM1L/TERT have been associated with increased risk, indicating that genes involved in telomere maintenance and cell cycle regulation can also play a role ^[8]. While these findings often pertain to malignant forms, the identification of genetic variants, such as those near GATA3 implicated in the inherited susceptibility of benign prostatic hyperplasia, provides a direct parallel for the genetic basis of benign neoplastic growth in other organ systems, including the digestive tract ^[2]. Such inherited predispositions mean that individuals carrying specific combinations of these genetic variants may have a higher inherent risk of developing benign neoplasms.

Gene-Environment Interactions and Population-Specific Influences

The development of benign digestive system neoplasms is not solely determined by genetics but often involves complex interactions between an individual’s genetic makeup and environmental exposures. While specific environmental triggers for benign digestive system neoplasms are not extensively detailed in all genetic studies, research on related conditions, such as certain upper aerodigestive tract cancers, points to the combined effect of genetic susceptibility and external factors ^[3]. For example, the strong genetic determinants observed for nasopharyngeal carcinoma in individuals of Chinese ancestry suggest that a genetic predisposition within specific populations may interact with unique regional environmental factors, leading to a higher incidence of disease^[8]. These interactions can modulate gene expression, alter cellular responses to damage, or influence immune surveillance, collectively contributing to the initiation or progression of benign cellular proliferations.

Geographic influences and socioeconomic factors, though not always directly causal for benign neoplasms, can shape the environmental landscape to which genetically predisposed individuals are exposed. Dietary patterns, exposure to certain toxins, or prevalence of specific infections, which vary by region and socioeconomic status, could act as co-factors that trigger or accelerate the growth of benign lesions in individuals with inherited susceptibilities. The identification of population-specific genetic risk alleles underscores the importance of considering both the inherited background and the specific environmental milieu in understanding the etiology of benign digestive system neoplasms.

The incidence of benign digestive system neoplasms, like many other proliferative conditions, tends to increase with age, suggesting that age-related physiological changes are significant contributory factors. As individuals age, the accumulation of cellular damage, declining immune surveillance, and alterations in cellular repair mechanisms can create an environment conducive to abnormal cell growth. While specifically detailed for benign prostatic hyperplasia, the principle that advanced age is a key determinant in the development of benign neoplastic conditions likely extends to similar growths within the digestive system ^[2]. This age-dependent increase in risk highlights the cumulative impact of various intrinsic and extrinsic factors over a lifetime.

Beyond age, other factors such as existing comorbidities or long-term medication use could potentially influence the risk of benign digestive system neoplasms. Although not explicitly detailed for benign digestive system neoplasms in the provided studies, chronic inflammation, hormonal imbalances, or immune dysregulation associated with various health conditions can alter the microenvironment of digestive tissues, promoting cellular proliferation. Similarly, certain medications might have subtle long-term effects on cellular growth or differentiation, although specific examples linking medication effects directly to benign digestive system neoplasms are not provided in the current research.

Biological Background

Genetic Predisposition and Regulatory Networks

Genetic factors significantly contribute to an individual’s susceptibility to various conditions, including abnormal tissue growths. Research has identified specific genetic variants, or polymorphisms, that are associated with an altered risk of neoplasm development^[4]. These variants can influence gene functions and regulatory elements, thereby modulating gene expression patterns critical for cell growth and differentiation. For instance, specific loci within the HLA region have been implicated in susceptibility to certain neoplasms, highlighting the role of the immune system’s antigen recognition in disease etiology^[5].

Beyond individual genetic variants, the interplay of multiple genes and their regulatory elements forms complex networks that govern cellular behavior. Epigenetic modifications, which alter gene expression without changing the underlying DNA sequence, can also contribute to the development of neoplasms by impacting chromatin structure and gene accessibility. Studies on related conditions emphasize how genetic predispositions in genes like SH2B3 and TSHZ1 can influence susceptibility within the digestive tract, indicating broader genetic contributions to tissue abnormalities ^[4].

Cellular Homeostasis and Molecular Pathways

Maintaining cellular homeostasis is crucial for preventing abnormal tissue growth. Disruptions in key molecular and cellular pathways, such as signaling cascades and metabolic processes, can lead to uncontrolled cell proliferation and impaired cell death, which are foundational steps in neoplasm formation. Critical biomolecules, including various enzymes, receptors, hormones, and transcription factors, regulate these pathways, orchestrating cellular functions like growth, division, and repair. For example, theCLPTM1L/TERTlocus has been associated with altered cellular processes that contribute to neoplasm risk, suggesting its involvement in maintaining genomic stability and telomere length^[8].

Regulatory networks involving these biomolecules dictate how cells respond to internal and external stimuli. When these networks are perturbed, either through genetic variants or environmental factors, cells may lose their normal growth constraints. Such disruptions can lead to the accumulation of cells, forming a neoplasm. The general principles of disrupted cellular signaling and metabolic control, as observed in studies of other neoplasms, underscore the importance of these pathways in maintaining tissue integrity and preventing abnormal growths.

Tissue-Specific Manifestations and Pathophysiological Processes

Neoplasms manifest with organ-specific effects, reflecting the unique cellular composition and physiological functions of different tissues within the digestive system. The digestive tract, with its diverse array of specialized cells and constant exposure to various stimuli, presents distinct environments for neoplasm development. Pathophysiological processes can include developmental aberrations or homeostatic disruptions specific to the digestive organs, leading to localized abnormal growths. For example, studies investigating conditions like Barrett’s esophagus highlight how metaplastic changes in esophageal lining can create a predisposition for abnormal cell proliferation, even if it’s a precancerous state^[6].

Tissue interactions and the broader systemic consequences of abnormal growths can vary widely depending on the organ affected. For instance, genetic susceptibility to conditions affecting the colorectal region involves specific loci that impact the integrity and function of intestinal tissues ^[4]. While the outcomes discussed in these contexts often relate to progressive disease, the underlying mechanisms of initial tissue changes and cellular dysregulation are pertinent to understanding any form of abnormal growth within the digestive system. Compensatory responses by the surrounding healthy tissue may attempt to mitigate the effects of the neoplasm, but these responses can also be overwhelmed, leading to further tissue changes.

Population Studies

Population studies are crucial for understanding the prevalence, incidence, and genetic underpinnings of various conditions across diverse human groups. These large-scale investigations leverage extensive cohorts and advanced genomic techniques to identify genetic susceptibility factors, observe temporal patterns, and explore variations influenced by ancestry and geography.

Large-Scale Cohort and Biobank Investigations

The power of population studies often lies in their ability to analyze vast datasets from major population cohorts and biobanks, leading to the identification of genetic variants associated with disease risk. Studies utilizing efficient genome-wide association (GWAS) methods in biobanks, sometimes employing techniques like topic modeling, have successfully identified multiple novel disease loci^[9]. For conditions such as follicular lymphoma, comprehensive GWAS efforts involving international collaborations have identified several susceptibility loci outside the HLA region, demonstrating the impact of large sample sizes and international participant recruitment on discovering genetic predispositions ^[10]. These methodologies are essential for detecting genetic variants that may individually exert small effects but collectively contribute to disease risk, enhancing the statistical power and generalizability of findings.

Further applications of these large-scale approaches include meta-analyses of GWAS, which have been instrumental in pinpointing common susceptibility polymorphisms for complex conditions like colorectal and endometrial cancer, identifying significant loci near genes such asSH2B3 and TSHZ1 ^[4]. Similarly, a GWAS specifically identified a common variant linked to an increased risk of endometrial cancer^[11]. Studies on benign prostatic hyperplasia (BPH) have also benefited from large cohorts, with research involving thousands of cases and controls revealing genetic variants implicated in inherited susceptibility and etiology ^[2]. These extensive studies, often encompassing broad demographic representation, are fundamental for uncovering genetic associations and understanding the population-level implications of specific genetic markers.

Geographic and Ancestry-Specific Variations

Genetic predispositions and disease patterns frequently exhibit significant differences across various geographic regions and ancestral groups, highlighting the importance of cross-population comparisons. Nasopharyngeal carcinoma (NPC), for instance, demonstrates strong genetic determinants involving the HLA class I antigen recognition groove, with particularly notable associations in individuals of Chinese ancestry^[12]. Further research within Chinese populations has identified a novel locus within CLPTM1L/TERTassociated with NPC risk, underscoring the necessity of population-specific genetic studies to accurately capture the genetic landscape of a disease^[8]. Such findings illustrate that genetic susceptibility is not uniform globally and requires tailored investigations to understand ethnic and geographic specificities.

To address this variability, large-scale international consortia are vital for capturing diverse genetic backgrounds. The INHANCE consortium, which conducted a GWAS for upper aerodigestive tract (UADT) cancers, included participants from numerous countries across Europe, North America, and other regions, enabling a more comprehensive understanding of genetic risk factors across varied populations ^[3]. Similarly, studies on follicular lymphoma and colorectal/endometrial cancer have leveraged extensive international collaborations, with researchers from institutions in Spain, Australia, Denmark, France, Italy, and the UK contributing to the identification of genetic variants, thereby providing insights into how genetic risk factors may differ or be shared across global populations^[10]. These efforts are crucial for revealing population-specific effects and refining our understanding of disease etiology worldwide.

Epidemiological Insights and Genetic Associations

Epidemiological studies, particularly those employing GWAS, are instrumental in establishing genetic associations and characterizing disease prevalence and incidence patterns within populations. For example, GWAS have revealed specific genetic susceptibilities for different glioma subtypes, identifying distinct genetic underpinnings for glioblastoma and non-glioblastoma tumors^[13]. Genetic variants on chromosome 7p11.2 (near EGFR) and at regions on chromosomes 1 and 9 have also been linked to an increased risk of glioma ^[14]. These studies typically employ case-control designs, meticulously comparing genetic markers between affected individuals and healthy controls to identify statistically significant associations, thereby contributing to our understanding of demographic factors influencing disease risk.

Methodological rigor is paramount in these investigations, especially when exploring complex genetic architectures. Research into follicular lymphoma has uncovered allelic heterogeneity at the 6p21.32 locus, suggesting a shared genetic susceptibility with diffuse large B-cell lymphoma ^[15]. Such findings highlight the intricate nature of genetic risk, often involving multiple loci with small individual effects that collectively influence disease susceptibility. While large sample sizes and advanced statistical methods, including meta-analyses, enhance the statistical power and generalizability of findings, considerations of study design, sample representativeness, and potential confounding factors remain critical for ensuring the robustness and validity of the observed epidemiological associations.

Frequently Asked Questions About Benign Digestive System Neoplasm

These questions address the most important and specific aspects of benign digestive system neoplasm based on current genetic research.

1. My parent had polyps. Will I get them too?

Yes, there’s a higher chance you might. The development of these growths involves “inherited susceptibility” and an individual’s unique genetic makeup. While not every polyp is purely inherited, having a close relative with benign digestive system neoplasms suggests you might share some of these genetic predispositions, making regular screening especially important for you.

2. Why do some people get polyps, but others don’t?

It’s often a combination of your unique genetic blueprint and environmental influences. These growths arise from uncontrolled cell proliferation, often driven by accumulated genetic mutations or epigenetic changes in cells. Some individuals are born with specific “genetic variants associated with inherited susceptibility,” making them more prone to these changes than others.

3. Can my diet really prevent these growths?

While genetics play a significant role, your diet, as an environmental factor, can certainly influence your risk. The article notes “complex interactions between genetic predisposition and environmental factors.” A healthy diet can support overall cellular health and might mitigate some of the genetic predispositions, though the exact interplay for specific foods is still a focus of research.

4. Does my ethnic background change my polyp risk?

Yes, it can. Research highlights the “population-specific nature of many genetic studies,” meaning certain genetic risk factors might be more prevalent or identified in particular ethnic groups. For example, studies on related conditions have identified specific genetic determinants within certain ancestries, suggesting your background could influence your specific genetic risks.

5. Is there a DNA test to check my risk?

Currently, there isn’t a single, comprehensive DNA test to predict your overall risk for allbenign digestive system neoplasms. While specific genetic variants are linked to increased susceptibility for some related conditions, the “broad spectrum of ‘benign digestive system neoplasm’ could encompass a heterogeneous group of conditions.” Research is ongoing to identify more genetic markers for personalized risk assessments.

6. If I live healthy, can I beat my family history?

Living a healthy lifestyle can significantly reduce your risk, but it’s not a guaranteed way to entirely “beat” a strong family history. You might inherit genetic predispositions, but the article emphasizes “complex interactions between genetic predisposition and environmental factors.” A healthy lifestyle can mitigate some genetic risks, but some “missing heritability” and genetic pathways are still being understood.

7. My sibling got polyps, but I haven’t. Why?

This illustrates the individual nature of genetic risk and “phenotypic heterogeneity.” Even within families, people inherit different combinations of genetic variants, and their environmental exposures can vary. You might have inherited different protective genes or adopted lifestyle habits that reduce your risk compared to your sibling, or your sibling might have specific genetic changes you don’t.

8. Does stress actually make me more susceptible?

The article points to “the potential influence of unmeasured environmental or gene-environment interactions” and “missing heritability.” While stress isn’t directly named, it’s a significant environmental factor that impacts overall health and inflammatory processes. This could interact with your genetic predispositions, but more research is needed to fully understand such complex connections.

9. Why do some polyps turn bad, but others don’t?

The potential for a benign growth to become cancerous depends on its type and further accumulated genetic mutations within its cells. Many benign polyps, especially adenomas, are considered “precancerous lesions” because they have the “potential to evolve into colorectal cancer if not removed.” This evolution is driven by additional genetic alterations that push the cells towards malignancy.

10. Why are these growths so common in my family?

Your family likely shares some of the genetic predispositions that make individuals more susceptible to these growths. The article states that their development involves “complex interactions between genetic predisposition and environmental factors.” If multiple family members have them, it strongly suggests a shared genetic background that increases the likelihood of developing these neoplasms, possibly combined with shared lifestyle or environmental exposures.

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] Na, R et al. “A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).” Prostate, 2017.

[2] Na, R. “A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).” Prostate, PMID: 28656603.

[3] McKay, J. D. “A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.” PLoS Genet, PMID: 21437268.

[4] Cheng, T. H. “Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.”Sci Rep, PMID: 26621817.

[5] Tang, M et al. “The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.” PLoS Genet, vol. 8, no. 11, 2012.

[6] Levine, D. M. et al. “A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus.”Nat Genet, 2013.

[7] Cheng, T. H. et al. “Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.”Sci Rep, 2015.

[8] Bei, J. X. “A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry.” Cancer Epidemiol Biomarkers Prev, PMID: 26545403.

[9] McCoy, Thomas H., et al. “Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.”Molecular Medicine, vol. 23, no. 1, 2017, pp. 292-300.

[10] Skibola, CF., et al. “Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.” American Journal of Human Genetics, 2014.

[11] Spurdle, AB., et al. “Genome-wide association study identifies a common variant associated with risk of endometrial cancer.”Nature Genetics, 2011.

[12] Tang, M. “The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.” PLoS Genet, PMID: 23209447.

[13] Melin, Beatrice S., et al. “Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.” Nature Genetics, vol. 49, no. 5, 2017, pp. 789-794.

[14] Sanson, Marc, et al. “Chromosome 7p11.2 (EGFR) variation influences glioma risk.” Human Molecular Genetics, vol. 20, no. 13, 2011, pp. 2697-2704.

[15] Smedby, Karin E., et al. “GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.” PLoS Genetics, vol. 7, no. 4, 2011, e1001378.