Gallbladder Neoplasm
A gallbladder neoplasm refers to any abnormal growth of cells within the gallbladder, a small organ located beneath the liver that stores and concentrates bile. These growths can be benign (non-cancerous) or malignant (cancerous). While benign growths like polyps are often asymptomatic and harmless, malignant neoplasms, primarily gallbladder cancer (adenocarcinoma), are aggressive and often associated with a poor prognosis due to late diagnosis.
The biological basis of gallbladder neoplasm involves uncontrolled cell proliferation in the gallbladder lining. This process is typically initiated by genetic mutations that disrupt normal cell growth and division pathways. Chronic inflammation, often linked to long-standing gallstones (cholelithiasis), is a significant risk factor, as it can lead to cellular damage and the accumulation of mutations over time. Other factors, such as specific genetic predispositions, exposure to certain environmental toxins, and conditions like anomalous pancreaticobiliary junction, can also contribute to the development of these neoplasms.
Clinically, gallbladder neoplasms pose a significant challenge. Early-stage gallbladder cancer often presents with non-specific symptoms, or no symptoms at all, leading to diagnosis at advanced stages when the disease has already spread. Symptoms, when present, can include abdominal pain, jaundice, unexplained weight loss, and nausea. Diagnosis typically involves imaging techniques such as ultrasound, CT scans, or MRI, sometimes followed by biopsy. Treatment options depend on the stage of the cancer and may include surgery (cholecystectomy), chemotherapy, radiation therapy, or palliative care. The prognosis for advanced gallbladder cancer remains poor, highlighting the need for earlier detection methods.
From a social perspective, gallbladder neoplasm, particularly its malignant form, represents a substantial public health concern. Its high mortality rate contributes to the global cancer burden. The disease disproportionately affects certain populations, with higher incidences observed in parts of South America, Asia, and Eastern Europe, suggesting geographic and ethnic risk factors. The emotional and financial toll on patients and their families, as well as the healthcare system, underscores the social importance of increased awareness, improved diagnostic tools, and more effective treatment strategies to combat this aggressive cancer.
Limitations
Section titled “Limitations”The current understanding of the genetic architecture underlying gallbladder neoplasm, particularly through genome-wide association studies (GWAS), is subject to several methodological and interpretative limitations. These constraints are inherent to complex disease research and warrant careful consideration when interpreting genetic associations.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Genetic studies of complex traits like gallbladder neoplasm often face challenges related to study design and statistical power. Achieving sufficiently large sample sizes is critical for robustly identifying genetic variants with modest effect sizes, and smaller cohorts can lead to inflated effect estimates for initially discovered associations[1]. This necessitates rigorous replication in independent populations to validate findings and prevent false positives, a common practice in the field [2]. Furthermore, while meta-analyses can enhance statistical power by combining data from multiple studies, they introduce complexities related to potential heterogeneity across study designs, populations, and phenotyping protocols, which must be carefully accounted for [3], [4].
The design of control cohorts also presents a significant consideration. The use of “generic” controls, or controls not perfectly matched to cases on all relevant demographic and environmental factors, can introduce subtle biases that might confound genetic associations [4]. Such biases can obscure true genetic signals or create spurious ones, impacting the reliability and interpretability of findings. Comprehensive study designs that minimize cohort bias and carefully select appropriate control groups are essential for accurately dissecting the genetic contributions to gallbladder neoplasm risk.
Generalizability and Phenotypic Heterogeneity
Section titled “Generalizability and Phenotypic Heterogeneity”A significant limitation in genetic research is the generalizability of findings across diverse populations. Many genetic association studies are conducted predominantly in populations of specific ancestries, making it challenging to directly extrapolate results to other ethnic groups [5]. Genetic architectures, including allele frequencies and linkage disequilibrium patterns, can vary considerably between populations, meaning that susceptibility loci identified in one group may not confer the same risk, or even be present, in another [6], [7]. This highlights the critical need for broader cross-population investigations to fully understand the global genetic landscape of gallbladder neoplasm.
Moreover, gallbladder neoplasm, like many cancers, can exhibit considerable phenotypic heterogeneity, encompassing various subtypes, stages, and molecular profiles. If genetic studies do not precisely define and stratify these distinct phenotypes, the power to detect specific genetic associations can be diminished. Broad phenotyping might dilute signals from variants truly associated with a particular subtype or progression pathway, leading to an incomplete understanding of the disease’s genetic underpinnings[8]. More granular phenotyping is crucial for uncovering the nuanced genetic contributions to different manifestations of gallbladder neoplasm.
Etiological Complexity and Remaining Knowledge Gaps
Section titled “Etiological Complexity and Remaining Knowledge Gaps”The etiology of gallbladder neoplasm is complex, extending beyond purely genetic factors to include environmental exposures and intricate gene-environment interactions. Current genetic studies often struggle to fully capture these non-genetic confounders and their interplay with genetic susceptibility, which can significantly influence disease risk and progression[4]. Overlooking these complex interactions can lead to an incomplete picture of disease causation and limit the utility of genetic findings for preventive or therapeutic strategies.
Furthermore, a common observation in the genetics of complex diseases is the phenomenon of “missing heritability,” where identified common genetic variants explain only a fraction of the estimated heritable risk. For gallbladder neoplasm, this suggests that a substantial portion of genetic susceptibility remains unaccounted for by typical GWAS approaches. This gap may be attributed to rarer genetic variants, structural variations, epigenetic modifications, or complex polygenic interactions that are not well-captured by current methodologies, indicating significant remaining knowledge gaps in understanding the complete genetic and environmental architecture of the disease.
Variants
Section titled “Variants”Genetic variations play a critical role in influencing individual susceptibility to various diseases, including gallbladder neoplasm. The variants discussed here are located within or near genes involved in fundamental cellular processes such as apoptosis, cell cycle control, cell adhesion, and signaling pathways, all of which are frequently dysregulated in cancer development. Understanding these associations can provide insights into the molecular mechanisms underlying gallbladder neoplasm.
Several variants are implicated in the regulation of cell death and division, processes central to cancer. Thers139351050 variant is associated with the DAPK1 gene, which encodes Death-associated protein kinase 1, a key enzyme in programmed cell death pathways. Dysregulation of DAPK1 can impair a cell’s ability to self-destruct when damaged, thereby promoting tumor survival. Similarly, the rs10953615 variant is linked to BUB3P1, a pseudogene related to BUB3, a protein involved in the mitotic checkpoint that ensures proper chromosome segregation during cell division. Alterations in these genes can lead to uncontrolled cell proliferation and genomic instability, which are hallmarks of malignancy [8].
Other variants influence genes involved in cell-cell communication and migration, processes critical for tissue organization and often subverted in cancer metastasis. Thers7504990 variant is located near DCC(Deleted in Colorectal Carcinoma), a gene known for its role as a netrin receptor in neuronal guidance and, importantly, as a tumor suppressor. Loss of DCC function is associated with increased invasiveness and metastasis in several cancers. Thers975334 variant is linked to CNTN4(Contactin 4), a cell adhesion molecule crucial for neural development, but also involved in cell-cell interactions that can affect tumor growth and spread. Variations in these genes can disrupt normal cellular architecture and promote the invasive properties of cancer cells, contributing to the aggressive nature of some gallbladder neoplasms[8].
Variants affecting various signaling and receptor functions also contribute to neoplasm risk. Thers115602890 variant is found near EPHB1(Ephrin receptor B1), a tyrosine kinase receptor that plays a role in cell migration, adhesion, and tissue patterning. Dysregulation of Ephrin signaling is frequently observed in cancer, influencing tumor growth and angiogenesis. Thers73161370 variant is associated with RXFP2(Relaxin/insulin-like family peptide receptor 2), a G protein-coupled receptor primarily involved in reproductive physiology but whose broader signaling roles could impact cellular processes relevant to cancer. Furthermore, thers77671828 variant is linked to NPFFR2(Neuropeptide FF receptor 2), another G protein-coupled receptor, which, while known for pain modulation, could also influence cellular growth and inflammatory responses relevant to cancer pathogenesis. These genetic variations can alter crucial signaling pathways that govern cell growth, survival, and invasion, processes that are often deranged in digestive system cancers like gallbladder neoplasm[9].
Finally, variants in less characterized genes or non-coding regions also warrant consideration. The rs77648787 variant is associated with NWD1(NACHT and WD repeat domain containing protein 1), a gene implicated in immune responses and inflammation, both of which are known to influence cancer development. Chronic inflammation, for instance, is a recognized risk factor for many cancers. Thers13294589 variant is linked to LINC03106, a long intergenic non-protein coding RNA. Such non-coding RNAs are increasingly recognized for their regulatory roles in gene expression and can function as oncogenes or tumor suppressors. Lastly, the rs6869388 variant is found in the vicinity of KIAA0825, a gene whose precise function is still under investigation but, like many genes, may contribute to fundamental cellular processes that, when altered, can promote neoplastic transformation. These variants, through their impact on inflammatory pathways or gene regulation, can collectively contribute to the complex etiology of gallbladder neoplasm[8].
Key Variants
Section titled “Key Variants”Identified Gallbladder Traits and Phenotypes
Section titled “Identified Gallbladder Traits and Phenotypes”While the comprehensive definition of a gallbladder neoplasm encompasses a range of abnormal growths, research focusing on deep phenotyping identifies specific gallbladder conditions as distinct phenotypes. Within a large health check-up cohort of Korean individuals, conditions such as Gall bladder polyp and Gall bladder adenomyomatosis have been cataloged as significant traits[10]. These represent definable structural or pathological alterations within the digestive system, crucial for characterizing the spectrum of gallbladder health and disease and enabling further investigation into their prevalence and associations[10].
Characterization and Nomenclature of Gallbladder Findings
Section titled “Characterization and Nomenclature of Gallbladder Findings”The terminology employed for gallbladder abnormalities includes key terms such as “Gall bladder polyp” and “Gall bladder adenomyomatosis,” which are recognized as distinct phenotypes in research studies [10]. A Gall bladder polyp, as a specific term, denotes a type of growth found within the gallbladder, representing an abnormal projection from its inner lining. Similarly, Gall bladder adenomyomatosis signifies a defined structural alteration of the gallbladder wall, distinguished from other conditions like cholecystitis or gallstones[10]. These terms are integral to the standardized vocabulary used in characterizing diverse digestive system traits within medical and research contexts.
Diagnostic Context and Research Identification
Section titled “Diagnostic Context and Research Identification”The identification of gallbladder conditions, including Gall bladder polyp and Gall bladder adenomyomatosis, is established through diagnostic approaches within deep phenotyping studies [10]. These conditions are operationalized as distinct traits for research purposes, allowing for their categorical assessment (presence or absence) in large populations, such as the 10,000 Korean individuals included in a health check-up cohort [10]. While specific measurement approaches or precise cut-off values for defining these particular traits are not detailed, their inclusion as phenotypes indicates their ascertainment through established clinical or imaging criteria for the purpose of phenome-wide association studies [10]. This framework allows for systematic investigation into their genetic and environmental associations.
Presentation and Detection of Gallbladder Neoplasms
Section titled “Presentation and Detection of Gallbladder Neoplasms”Gallbladder neoplasms, commonly presenting as polyps, are frequently identified incidentally during routine health check-ups within deep phenotyping cohorts [10]. This pattern of discovery indicates that these conditions are often asymptomatic in their early stages, minimizing the role of subjective symptom reporting for initial diagnosis. Objective imaging techniques serve as the primary measurement approach for detecting these polyps, underscoring the diagnostic significance of routine screenings for early identification despite the lack of overt clinical signs. The incidental nature of detection poses a diagnostic challenge, as the absence of clear symptoms can delay recognition until the neoplasm is more advanced.
Causes
Section titled “Causes”Genetic Predisposition and Phenotypic Associations
Section titled “Genetic Predisposition and Phenotypic Associations”The development of gallbladder neoplasm is an area of active investigation, with research efforts focused on identifying genetic susceptibility factors through comprehensive phenome-wide association studies (PheWAS)[10]. These studies leverage deep phenotyping from large health check-up cohorts to explore a wide range of human traits, including those related to the digestive system [10]. While specific genetic variants for gallbladder neoplasm are not detailed in the provided context, the PheWAS methodology is designed to uncover inherited variants and polygenic risk, suggesting a genetic component to the overall risk profile for gallbladder pathologies[10].
Associated Gallbladder Conditions
Section titled “Associated Gallbladder Conditions”Several specific conditions affecting the gallbladder are recognized as distinct traits within these extensive health research frameworks, potentially contributing to the broader risk of neoplasia [10]. These include gall bladder adenomyomatosis, gall bladder cholecystitis, gall bladder stone, and gall bladder polyp, all of which have been cataloged as digestive system traits in phenome-wide analyses [10]. The inclusion of these conditions underscores their importance in understanding the complex etiology of gallbladder health and disease, highlighting potential pathways that may influence the progression towards neoplastic changes[10].
Biological Background of Gallbladder Neoplasm
Section titled “Biological Background of Gallbladder Neoplasm”Gallbladder neoplasm refers to the abnormal growth of cells within the gallbladder, a small organ located beneath the liver that stores and concentrates bile. The development of such neoplasms is a complex process involving disruptions in normal cellular function, genetic alterations, and interactions within the organ’s unique physiological environment. Understanding these underlying biological mechanisms is crucial for comprehending the initiation and progression of gallbladder cancer.
Overview of Gallbladder Pathophysiology and Precursors
Section titled “Overview of Gallbladder Pathophysiology and Precursors”The gallbladder plays a crucial role in the digestive system by storing and releasing bile, which aids in fat digestion. Disruptions to the normal homeostatic processes of this organ are often precursors to neoplastic changes. Gallbladder disease, particularly cholelithiasis (gallstones), is epidemiologically linked to the development of gallbladder cancer[11]. These gallstones can cause chronic irritation and inflammation, creating a microenvironment conducive to cellular transformation and the eventual emergence of neoplasia.
Another significant pathological finding is the presence of gallbladder polyps, identified as a distinct trait in large-scale phenome-wide association studies [10]. While many polyps are benign, certain types and sizes carry an increased risk of malignant transformation, serving as potential precursors to gallbladder neoplasm. The progression from chronic inflammation or benign polyps to invasive cancer involves a series of cellular and tissue-level changes, highlighting the importance of monitoring these conditions for early detection and intervention.
Molecular and Cellular Mechanisms in Gallbladder Neoplasia
Section titled “Molecular and Cellular Mechanisms in Gallbladder Neoplasia”The cellular and molecular underpinnings of neoplasia in digestive organs, including the gallbladder, involve intricate pathways that regulate cell growth, survival, and differentiation. Cancer stem cells are a critical population within tumors, believed to be responsible for tumor initiation, sustained growth, and resistance to therapy. Key biomolecules, such as laminins, have been identified as crucial partners with cancer stem cells, influencing their behavior and contributing to the malignant phenotype through various signaling and regulatory networks[12]. These interactions highlight the complex interplay of structural components and signaling molecules in driving cancer progression.
Furthermore, cellular defense mechanisms and their subversion are central to the pathophysiology of cancer. Human multidrug resistance ABCB and ABCG transporters are critical proteins that function as part of a chemoimmunity defense system, actively pumping various substances out of cells[13]. In the context of neoplasia, altered function or overexpression of these transporters can lead to multidrug resistance, a significant challenge in cancer treatment, by disrupting normal cellular metabolic processes and protective functions.
Genetic Susceptibility and Interconnections with Digestive Disorders
Section titled “Genetic Susceptibility and Interconnections with Digestive Disorders”Genetic mechanisms are fundamental in determining an individual’s susceptibility to various digestive disorders, including those that can precede gallbladder neoplasm. Research, including cross-disorder studies, has focused on identifying causal relationships, shared genetic variants, and common genes across a spectrum of 21 digestive disorders[9]. This approach recognizes that complex genetic regulatory networks and specific gene expression patterns can contribute to susceptibility across multiple related conditions, indicating a broader genetic predisposition to gastrointestinal pathologies.
The identification of shared genetic determinants among digestive disorders suggests common underlying pathophysiological processes or interacting pathways that may influence cancer risk. For instance, while specific genetic loci for gallbladder neoplasm are not extensively detailed in the provided context, the concept of shared genetic susceptibility with other digestive cancers, such as colorectal or endometrial cancer linked to genes like SH2B3 and TSHZ1[3], or even specific variants for nasopharyngeal carcinoma involving the HLA region [5], or oral cancer[14], points to broader genetic influences on cancer risk. These shared genetic elements can impact various cellular functions and regulatory networks, increasing an individual’s overall predisposition to certain types of neoplasia.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Genetic Susceptibility and Gallbladder Pathologies
Section titled “Genetic Susceptibility and Gallbladder Pathologies”Phenome-wide association studies have investigated a spectrum of conditions, including gallbladder cholecystitis and gallbladder polyps, as identifiable traits . These findings are crucial for understanding the complex etiology of gallbladder neoplasm, suggesting shared genetic or environmental predispositions that link these conditions. Such epidemiological insights enable more precise risk stratification, allowing clinicians to identify individuals at a higher risk for developing gallbladder neoplasm based on their genetic profile and co-occurring conditions.
Beyond direct gallbladder conditions, the same study revealed associations with other digestive system traits like fatty liver, atrophic gastritis, and intestinal metaplasia of the stomach[10]. These broader associations highlight potential systemic factors or overlapping pathophysiological pathways that could influence gallbladder health and neoplastic transformation. Integrating these insights into clinical practice can enhance risk assessment models, moving towards personalized medicine approaches that consider an individual’s complete phenomic and genetic landscape for targeted prevention strategies.
Diagnostic and Prognostic Indicators
Section titled “Diagnostic and Prognostic Indicators”The identification of specific gallbladder pathologies, such as gall bladder polyps and adenomyomatosis, serves as a critical diagnostic utility in the context of gallbladder neoplasm[10]. These conditions, often detected during routine health check-ups or investigations for related symptoms, can represent precursor lesions or indicators of increased risk. Early and accurate diagnosis of these associated conditions is paramount for timely intervention and for establishing a baseline for monitoring.
Furthermore, the presence and characteristics of gall bladder polyps or adenomyomatosis carry significant prognostic value, aiding in the prediction of disease progression and potential malignant transformation[10]. Regular monitoring strategies for individuals diagnosed with these conditions are essential to track changes over time, assess treatment response, and identify any long-term implications. This proactive approach, informed by identified associations, can significantly improve patient outcomes by facilitating early detection of neoplasm development.
Implications for Personalized Patient Management
Section titled “Implications for Personalized Patient Management”The comprehensive phenotyping from studies like the Korean health check-up cohort underscores the potential for personalized medicine in managing gallbladder neoplasm risk[10]. By leveraging genetic and phenomic data, healthcare providers can develop tailored prevention strategies for high-risk individuals, which may include specific dietary recommendations, lifestyle modifications, or more frequent and advanced screening protocols. This moves beyond a one-size-fits-all approach to patient care.
Integrating knowledge of identified comorbidities and genetic predispositions allows for refined treatment selection and monitoring strategies. For instance, individuals with specific genetic markers or co-existing conditions like gall bladder stones or fatty liver might benefit from intensified surveillance or consideration of prophylactic interventions [10]. Such an evidence-based, personalized approach aims to optimize patient care pathways, enhance early detection efforts, and ultimately improve the long-term prognosis for individuals at risk of or diagnosed with gallbladder neoplasm.
Frequently Asked Questions About Gallbladder Neoplasm
Section titled “Frequently Asked Questions About Gallbladder Neoplasm”These questions address the most important and specific aspects of gallbladder neoplasm based on current genetic research.
1. My mom had gallbladder cancer. Does that mean I’ll get it too?
Section titled “1. My mom had gallbladder cancer. Does that mean I’ll get it too?”Not necessarily. While there can be specific genetic predispositions that run in families, it doesn’t guarantee you’ll develop it. Many factors, including chronic inflammation and environmental exposures, also play a significant role in developing these growths.
2. I’ve had gallstones for years. Does that mean I’m more likely to get gallbladder cancer?
Section titled “2. I’ve had gallstones for years. Does that mean I’m more likely to get gallbladder cancer?”Yes, having long-standing gallstones is a significant risk factor. The chronic inflammation they cause can lead to cellular damage and the accumulation of genetic mutations over time, increasing your risk for a gallbladder neoplasm.
3. I’m from South America. Does my background affect my risk for this cancer?
Section titled “3. I’m from South America. Does my background affect my risk for this cancer?”Yes, unfortunately, certain populations, including those in parts of South America, Asia, and Eastern Europe, show a higher incidence of gallbladder cancer. This suggests there can be geographic and ethnic genetic risk factors at play.
4. Can changing my diet or lifestyle really help prevent gallbladder cancer?
Section titled “4. Can changing my diet or lifestyle really help prevent gallbladder cancer?”While genetics play a role, lifestyle and environmental factors are also crucial. Minimizing exposure to certain environmental toxins and adopting habits that reduce chronic inflammation can help, as these factors interact with your genetic susceptibility.
5. Is there a DNA test that can tell me my personal risk for gallbladder cancer?
Section titled “5. Is there a DNA test that can tell me my personal risk for gallbladder cancer?”Currently, there isn’t a single, definitive DNA test that can tell you your precise personal risk. The genetic architecture of gallbladder neoplasm is complex, involving many different genetic variants, environmental influences, and gene-environment interactions that are still being understood.
6. Why do some people with gallstones get cancer, but others don’t, even with similar issues?
Section titled “6. Why do some people with gallstones get cancer, but others don’t, even with similar issues?”This often comes down to individual genetic predispositions, specific types of inflammation, and other environmental or lifestyle factors. There’s a lot of complexity, and not all genetic contributions are fully understood, leading to what’s called “missing heritability.”
7. Could something in my environment, like pollution or chemicals, increase my risk for this?
Section titled “7. Could something in my environment, like pollution or chemicals, increase my risk for this?”Yes, exposure to certain environmental toxins can contribute to the development of gallbladder neoplasms. These toxins can cause cellular damage, which in turn can lead to the genetic mutations that initiate abnormal cell growth.
8. My sibling and I both have gallstones, but they seem fine. Does that mean I’m safe too?
Section titled “8. My sibling and I both have gallstones, but they seem fine. Does that mean I’m safe too?”Not necessarily. Even within families, genetic predispositions and how your body responds to inflammation can differ. The disease can also show phenotypic heterogeneity, meaning it can manifest differently even with similar risk factors.
9. Does having an anomalous pancreaticobiliary junction increase my risk?
Section titled “9. Does having an anomalous pancreaticobiliary junction increase my risk?”Yes, an anomalous pancreaticobiliary junction is a known risk factor. This condition can lead to abnormal bile flow and chronic inflammation, which can contribute to the cellular changes and genetic mutations that lead to neoplasm development.
10. If doctors find a polyp in my gallbladder, does that automatically mean I’ll get cancer?
Section titled “10. If doctors find a polyp in my gallbladder, does that automatically mean I’ll get cancer?”No, not all polyps are cancerous. Many are benign and harmless. However, some types of polyps, particularly those with certain genetic characteristics, can have a higher potential to become malignant over time, so they are often monitored closely.
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
Section titled “References”[1] Smedby, K. 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, April 2011.
[2] Skibola, C. F., et al. “Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.” The American Journal of Human Genetics, October 2, 2014.
[3] 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, vol. 5, Dec. 2015, 17561.
[4] McKay, J. D., et al. “A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.” PLoS Genetics, March 2011.
[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, Nov. 2012, e1003103.
[6] Sakaue, S., et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics.
[7] Lesseur, C., et al. “Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.” PLoS Genetics.
[8] Gentiluomo, M et al. “A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy.”Cancer, vol. 130, no. 1, 2024, pp. 69-79.
[9] Jiang, Y et al. “A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.” iScience, vol. 26, no. 12, 2023, p. 108343.
[10] Choe, E. K., et al. “Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.” Sci Rep, vol. 12, no. 1, 2022, p. 1930.
[11] Stinton, L. M., and E. A. Shaffer. “Epidemiology of gallbladder disease: cholelithiasis and cancer.”Gut Liver, vol. 6, 2012.
[12] Qin, Y., et al. “Laminins and cancer stem cells: Partners in crime?”Semin. Cancer Biol., 2017.
[13] Sarkadi, B., et al. “Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system.” Physiol. Rev., vol. 86, 2006, pp. 1179–1236.
[14] Bau, D. T. “A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan.”Int J Mol Sci.