Liver Cancer
Liver cancer refers to the uncontrolled growth of abnormal cells within the liver. It encompasses primary liver cancers, which originate in the liver itself, and metastatic liver cancers, which occur when cancer cells spread to the liver from other parts of the body. The most prevalent type of primary liver cancer is hepatocellular carcinoma (HCC), arising from the main liver cells (hepatocytes). Other less common primary types include cholangiocarcinoma (bile duct cancer) and angiosarcoma. Globally, liver cancer represents a significant public health challenge and is a leading cause of cancer-related mortality, with its incidence and prevalence varying considerably across different geographic regions due to diverse risk factor exposures.
The biological basis of liver cancer is complex, often rooted in chronic liver inflammation and damage. Major risk factors include chronic infections with Hepatitis B virus (HBV) and Hepatitis C virus (HCV), prolonged excessive alcohol consumption, and nonalcoholic fatty liver disease (NAFLD). These conditions can progressively lead to liver cirrhosis, a severe scarring of the liver tissue, which is the strongest predisposing factor for HCC. At a molecular level, liver cancer development involves the accumulation of genetic mutations and epigenetic alterations that disrupt normal cellular processes such as growth, division, and programmed cell death. Genetic predisposition also plays a role, with specific single nucleotide polymorphisms (SNPs) and inherited genetic variations influencing an individual’s susceptibility. For instance, research has identified genetic variants associated with the histological features of nonalcoholic fatty liver disease, a condition that can progress to liver cancer in some individuals[1]. These genetic factors can modulate pathways related to inflammation, fibrosis, and metabolism, thereby impacting overall cancer risk.
Clinically, liver cancer poses significant diagnostic and therapeutic challenges. Symptoms often manifest only in advanced stages, making early detection difficult. Diagnosis typically involves a combination of imaging techniques (such as ultrasound, CT, and MRI scans), blood tests (including tumor markers like alpha-fetoprotein), and sometimes a liver biopsy for definitive confirmation. Treatment strategies are highly individualized, depending on the cancer stage, the patient’s liver function, and overall health. Options may include surgical resection, liver transplantation, local ablative therapies, chemotherapy, radiation therapy, and more recently, targeted therapies and immunotherapy. Despite advancements, the prognosis for liver cancer, particularly HCC, remains poor for many patients, largely due to late-stage diagnosis and the aggressive nature of the disease, highlighting the critical need for improved screening and early intervention strategies, especially in high-risk populations.
The social importance of liver cancer is profound, contributing substantially to the global burden of disease and mortality. It impacts millions of individuals and families worldwide, leading to considerable loss of life and reduced quality of life. The disease disproportionately affects certain populations, reflecting the varied global distribution of its primary risk factors, such as high rates of HBV in parts of Asia and Africa, and increasing rates of HCV and NAFLD in Western countries. Public health efforts are crucial for prevention, including vaccination programs against HBV, screening and treatment for HCV, promotion of healthy lifestyles to mitigate NAFLD, and campaigns to reduce alcohol intake. A deeper understanding of the genetic underpinnings of liver cancer, including the identification and characterization of relevant SNPs, is essential for developing personalized risk assessment tools, targeted prevention strategies, and more effective therapeutic interventions, ultimately aiming to alleviate the immense societal impact of this disease.
Limitations
Section titled “Limitations”Research into the genetic underpinnings of liver cancer, while advancing rapidly, faces several inherent limitations that influence the interpretation and generalizability of findings. These limitations span methodological constraints, challenges in phenotypic definition, and the complex multifactorial nature of the disease. Acknowledging these aspects is crucial for a balanced understanding of current knowledge and for guiding future research directions.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Studies aimed at identifying genetic risk factors for liver cancer often rely on large-scale genetic association studies, which, despite significant efforts, may still be limited by insufficient sample sizes to detect all susceptibility variants, especially those with small effect sizes[2]. The power to identify additional risk variants is directly tied to increasing sample size and comprehensive SNP coverage through meta-analyses[2]. Furthermore, the robust replication of initial findings in independent cohorts is critical for validating associations and preventing the propagation of spurious results, underscoring the necessity for extensive replication efforts to confirm identified genetic loci [2].
The design of genetic association studies for liver cancer must also contend with complex statistical challenges, such as population stratification, where ancestral differences among study participants can lead to false-positive associations if not properly accounted for[3]. Advanced statistical methods, like principal component analysis, are essential for correcting such biases, but their application requires careful consideration to ensure accurate results [3]. Additionally, the integration of data from multiple studies through imputation-driven meta-analyses introduces its own set of practical aspects and complexities that can influence the comprehensive interpretation of overall findings [4].
Generalizability and Phenotypic Definition
Section titled “Generalizability and Phenotypic Definition”A significant limitation in understanding the genetic architecture of liver cancer is the potential for varying genetic influences across different ancestral populations. While some studies might assume common relative risks for genetic variants, the frequencies of alleles and genotypes can differ substantially between populations[5]. This heterogeneity impacts the generalizability of findings, meaning that genetic risk factors identified in one population may not translate directly or with the same effect size to others, necessitating diverse and inclusive study cohorts to capture a global understanding of genetic susceptibility[6].
Defining the precise phenotype of liver cancer and related liver conditions presents another challenge. For instance, studies investigating genetic variants associated with nonalcoholic fatty liver disease (NAFLD) specifically examine “histologic features,” highlighting the granularity and complexity involved in accurate phenotypic characterization[1]. The impact of common regulatory variation on gene expression can also be cell type-dependent, indicating that the biological effects of genetic variants may vary based on specific cellular contexts within the liver, further complicating phenotype-genotype correlations and the precise mapping of genetic associations to disease mechanisms[7].
Etiological Complexity and Unexplored Factors
Section titled “Etiological Complexity and Unexplored Factors”Current genetic studies primarily focus on identifying common genetic variants, yet the etiology of liver cancer is multifaceted and likely involves significant contributions from environmental exposures and their interactions with genetic predispositions. Factors such as diet, lifestyle, viral infections, and exposure to toxins are critical but often not fully captured or integrated into genetic association models. This omission means that a substantial portion of the heritability and overall risk for liver cancer remains unexplained by common genetic variants alone, pointing to a broader range of causal factors that warrant comprehensive investigation.
Despite the identification of susceptibility loci, a significant knowledge gap persists in fully elucidating the functional mechanisms by which these genetic variants contribute to liver cancer development. Simply identifying an association does not explain the biological pathway or the precise cellular and molecular changes induced by the variant. Understanding how common regulatory variation impacts gene expression in a cell-type dependent manner is crucial for translating genetic findings into actionable biological insights and potential therapeutic targets[7]. The ultimate goal is to move beyond mere association to a comprehensive mechanistic understanding of liver cancer’s genetic underpinnings.
Variants
Section titled “Variants”Variants within the PNPLA3 gene, particularly rs738409 and rs738408 , play a significant role in lipid metabolism and are strongly associated with the development and progression of liver diseases, including an increased risk for liver cancer. ThePNPLA3gene encodes patatin-like phospholipase domain-containing protein 3, an enzyme primarily involved in the hydrolysis of triglycerides within fat cells and liver cells. The single nucleotide polymorphism (SNP)rs738409 , also known as I148M due to an isoleucine-to-methionine change at position 148, is a well-studied variant that alters the protein’s function. This alteration reduces the enzyme’s ability to break down triglycerides, leading to their accumulation within the liver, a condition known as hepatic steatosis or fatty liver disease[8]. Studies have consistently demonstrated a strong association between the rs738409 C→G polymorphism and increased hepatic fat levels, as well as elevated plasma levels of alanine aminotransferase (ALT), a common indicator of liver damage[1].
Beyond basic fat accumulation, genetic variations in PNPLA3, including rs738409 and other associated variants like rs738408 , are critically linked to the more severe histological features of nonalcoholic fatty liver disease (NAFLD)[1]. These include steatosis (fatty liver), inflammation, and fibrosis, which collectively contribute to the Nonalcoholic Steatohepatitis (NASH) Activity Score (NAS)[1]. Research indicates that the PNPLA3genotype can significantly influence the degree of steatosis, liver inflammation, and the severity of fibrosis, which is the scarring of liver tissue[1]. While not always directly associated with steatohepatitis or ballooning in all studies, these progressive liver pathologies, driven in part by PNPLA3variants, are well-established precursors to more advanced liver diseases, including cirrhosis and hepatocellular carcinoma (HCC), the most common form of liver cancer. Therefore, these genetic predispositions represent a crucial factor in assessing an individual’s risk for severe liver complications.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs738408 rs738409 | PNPLA3 | platelet crit hematocrit hemoglobin measurement aspartate aminotransferase measurement response to combination chemotherapy, serum alanine aminotransferase amount |
| rs56255430 | MAU2 - GATAD2A | glomerular filtration rate blood protein amount anxiety measurement, low density lipoprotein cholesterol measurement depressive symptom measurement, low density lipoprotein cholesterol measurement social deprivation, triglyceride measurement |
| rs3828802 | HLA-DQB1 | liver cancer |
| rs559235319 | CASC9 | liver cancer |
| rs28891471 rs28891474 | HLA-DQB1 - MTCO3P1 | liver cancer |
| rs144048895 | LMCD1-AS1 | liver cancer |
| rs148887053 | YPEL1 - MAPK1 | liver cancer |
| rs35624376 | KLHL8 | liver cancer |
| rs8103142 | IFNL3 | liver cancer |
Classification, Definition, and Terminology
Section titled “Classification, Definition, and Terminology”Core Definitions and Nomenclature in Cancer Research
Section titled “Core Definitions and Nomenclature in Cancer Research”Cancer, as exemplified by various forms such as prostate, breast, lung, pancreatic, ovarian, gastric, esophageal squamous cell, and urinary bladder cancers, refers to a class of diseases characterized by abnormal cellular processes[9]. A crucial aspect of understanding these malignancies involves identifying “susceptibility loci,” which are specific genetic regions associated with an elevated risk of developing the disease[10]. The presence of “familial aggregation” and the involvement of “genetic factors” further highlight the hereditary predisposition observed in some cancers, such as pancreatic cancer[11].
The conceptual framework for cancer often involves understanding its pathogenesis, which can be defined by specific molecular alterations. For instance, pancreatic cancers are characterized by “somatic mutations in genes INK4A(CDKN2A), TP53, DPC4, BRCA1/2, STK11, APC, KRAS and ATM and PALB2”[11]. This detailed genetic and molecular nomenclature provides precise operational definitions for subtypes of cancer, informing both research and potential diagnostic strategies by identifying key genetic drivers of the disease.
Histological and Molecular Diagnostic Approaches
Section titled “Histological and Molecular Diagnostic Approaches”Diagnostic criteria for diseases affecting the liver, such as nonalcoholic fatty liver disease, incorporate “histologic features”[1], implying that microscopic examination of tissue samples is a fundamental measurement approach for characterizing the condition. This tissue-level assessment provides visual and structural information crucial for diagnosis and grading. Complementing this, for various cancers, molecular diagnostic criteria involve identifying specific genetic mutations. For example, the presence of “somatic mutations in genes INK4A(CDKN2A), TP53, DPC4, BRCA1/2, STK11, APC, KRAS and ATM and PALB2” serves as a diagnostic marker in pancreatic cancer[11].
These measurement approaches contribute to a comprehensive understanding of disease traits, moving beyond macroscopic observations to cellular and molecular levels. Operational definitions derived from these criteria allow for standardized assessment and classification of disease, enabling consistent diagnosis and research. The integration of histological and molecular findings provides a robust framework for delineating disease characteristics and severity.
Classification Systems in Genetic Epidemiology
Section titled “Classification Systems in Genetic Epidemiology”Disease classification in a research context often relies on genetic epidemiology, particularly through “genome-wide association studies” (GWAS)[1]. These studies systematically identify “variants associated with histologic features of nonalcoholic Fatty liver disease”[1] or “susceptibility loci” for various cancers [9]. The resulting classifications categorize individuals based on their genetic predisposition, offering insights into disease etiology and risk stratification. This categorical approach identifies specific genetic markers that can be used to understand disease subtypes or risk groups.
Research criteria for defining significant genetic associations are stringent, employing specific statistical methods and “conservative (p < 0.05/10-6 = 5 × 10-8) thresholds to define genome-wide significance” [12]. These rigorous cut-off values are essential for establishing the credibility of identified “susceptibility loci” [10], ensuring that reported genetic associations are robust. This standardized approach to statistical significance helps to classify genetic variants reliably and contributes to a robust nosological system for genetically influenced diseases.
There is no information about the signs and symptoms of liver cancer in the provided context.
Causes of Liver Cancer
Section titled “Causes of Liver Cancer”Liver cancer, a complex disease, arises from a combination of genetic predispositions and underlying liver conditions that can progress over time. Research into various cancers highlights the multifactorial nature of disease development, with genetic variations playing a significant role in an individual’s susceptibility.
Genetic Susceptibility and Liver Health
Section titled “Genetic Susceptibility and Liver Health”Genetic factors contribute significantly to an individual’s risk of developing various diseases, including those affecting the liver. Genome-wide association studies (GWAS) have been instrumental in identifying numerous common genetic variants that influence disease susceptibility. These studies, conducted across a range of cancers such as prostate, lung, breast, ovarian, and pancreatic cancers, demonstrate how inherited variants and polygenic risk contribute to disease development, often through subtle effects on gene function or expression.[6] Such findings underscore the importance of genetic makeup in predisposing individuals to specific health challenges.
Regarding liver health specifically, research has identified genetic variants associated with the histological features of nonalcoholic Fatty Liver Disease (NAFLD). These variants can influence the development and progression of NAFLD, a condition characterized by fat accumulation within the liver cells. Understanding these specific genetic predispositions is crucial for identifying individuals at higher risk for liver pathologies and for elucidating the molecular mechanisms driving liver disease.[1]
The Role of Underlying Liver Pathologies
Section titled “The Role of Underlying Liver Pathologies”Nonalcoholic Fatty Liver Disease (NAFLD) represents a significant underlying pathology that can influence the long-term health of the liver. This condition is characterized by distinct histological features, which are themselves influenced by specific genetic variants. The interplay between an individual’s genetic profile and the development of these histological characteristics underscores how inherited factors contribute to the severity and progression of liver conditions.[1]Such predispositions to chronic liver conditions are critical in understanding the broader context of liver disease development.
Genetic Underpinnings of Liver Disease and Cancer Susceptibility
Section titled “Genetic Underpinnings of Liver Disease and Cancer Susceptibility”Genetic predisposition plays a significant role in the risk of various complex diseases, including certain cancers and liver pathologies. Genome-wide association studies (GWAS) have been instrumental in identifying specific genetic variants and susceptibility loci across the human genome that are associated with an increased likelihood of developing conditions such as prostate, lung, breast, ovarian, colorectal, and pancreatic cancers [6]. These identified regions often harbor genes or regulatory elements whose altered function can contribute to disease development, highlighting the inherited component of disease risk.
Beyond simple presence, these genetic variations can influence gene expression patterns in a cell type-dependent manner, thereby affecting cellular functions and regulatory networks [7]. In the context of liver health, specific genetic variants have been found to be associated with the histologic features of nonalcoholic fatty liver disease (NAFLD)[1]. These associations suggest that inherited genetic factors can modulate the molecular landscape within liver cells, potentially influencing metabolic processes and contributing to the development of liver disease, which can be a precursor to more severe conditions like liver cancer.
Pathophysiological Processes and Tissue Remodeling in Liver Disease
Section titled “Pathophysiological Processes and Tissue Remodeling in Liver Disease”The liver, a vital organ responsible for numerous metabolic and detoxification functions, can undergo significant pathophysiological changes in response to various stressors. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver conditions characterized by the accumulation of fat in liver cells, which can progress to inflammation, fibrosis, and severe liver damage. Research has identified genetic variants associated with the distinct histologic features observed in NAFLD[1]. These histological changes, such as steatosis and inflammation, represent disruptions in normal liver homeostasis and cellular function.
Such alterations at the tissue level indicate underlying disease mechanisms that impair the liver’s ability to maintain its critical roles, leading to a cascade of cellular dysfunctions. These disruptions can include altered metabolic processes and compromised cellular functions within the hepatocytes, affecting the overall organ-level biology. The progressive nature of these changes underscores the importance of understanding the interplay between genetic factors and environmental influences in the development of chronic liver diseases that can ultimately lead to serious outcomes like liver cancer.
Molecular Regulation and Cellular Dynamics in Disease Progression
Section titled “Molecular Regulation and Cellular Dynamics in Disease Progression”At a fundamental molecular level, the development and progression of diseases like those affecting the liver are intricately linked to the precise regulation of gene expression and the activity of cellular pathways. Common genetic variations can exert their influence by impacting how genes are expressed, leading to alterations in the abundance or activity of critical proteins and enzymes [7]. These changes can disrupt the delicate balance of regulatory networks within cells, potentially affecting signaling pathways and metabolic processes that are essential for normal cellular function and liver health.
Such molecular disruptions can lead to compromised cellular functions, where cells may fail to perform their specialized tasks efficiently or respond appropriately to internal and external signals. While specific key biomolecules such as particular enzymes, receptors, or transcription factors directly implicated in liver cancer are not detailed in the available studies, the general principle of altered gene expression suggests downstream effects on the entire complement of cellular components. These molecular and cellular changes collectively contribute to the observable pathophysiological features of liver diseases and influence their trajectory.
Clinical Relevance for Liver Cancer
Section titled “Clinical Relevance for Liver Cancer”Genetic Predisposition and Risk Stratification
Section titled “Genetic Predisposition and Risk Stratification”Genetic studies contribute to understanding the inherited susceptibility to complex diseases, including those that can progress to liver cancer. For instance, genome-wide association studies (GWAS) have identified sequence variants associated with histologic features of nonalcoholic fatty liver disease (NAFLD)[1]. Given that NAFLD is a significant risk factor for hepatocellular carcinoma, identifying such variants could potentially help in stratifying individuals based on their genetic predisposition to severe liver disease and, consequently, their long-term risk for liver cancer. This approach supports the development of personalized medicine strategies aimed at identifying high-risk individuals who could benefit from targeted prevention efforts or early intervention to mitigate disease progression.
Prognostic Value and Disease Progression
Section titled “Prognostic Value and Disease Progression”Insights into genetic variants associated with underlying liver conditions, such as the histologic features of NAFLD, hold prognostic value for understanding disease progression towards more severe outcomes, including liver cancer[1]. Characterizing these genetic markers may allow for a more precise prediction of disease trajectories, helping clinicians anticipate which patients are more likely to experience rapid progression or develop complications. This understanding is crucial for tailoring monitoring strategies and potentially guiding treatment selection to improve long-term patient outcomes by addressing the root causes of liver damage before malignancy develops.
Diagnostic Utility and Comorbidity Management
Section titled “Diagnostic Utility and Comorbidity Management”Genetic findings can enhance the diagnostic utility for conditions that predispose to liver cancer, such as NAFLD. Identifying specific variants associated with NAFLD’s histologic features could offer non-invasive markers for assessing disease severity or progression, supplementing traditional diagnostic methods[1]. Furthermore, these genetic insights illuminate the complex interplay between related conditions and comorbidities. Effective management of underlying liver diseases like NAFLD, informed by genetic risk factors, is paramount for mitigating the overall burden of liver disease and reducing the incidence of liver cancer, thereby improving patient care.
Frequently Asked Questions About Liver Cancer
Section titled “Frequently Asked Questions About Liver Cancer”These questions address the most important and specific aspects of liver cancer based on current genetic research.
1. My parent had liver cancer. Will I get it too?
Section titled “1. My parent had liver cancer. Will I get it too?”Not necessarily, but your risk might be higher. You could have inherited genetic variations that make you more susceptible to conditions like chronic liver damage or inflammation, which are major drivers of liver cancer. However, lifestyle choices like managing alcohol intake and preventing viral infections are also very important for your personal risk.
2. Why did my sibling get liver cancer, but I didn’t?
Section titled “2. Why did my sibling get liver cancer, but I didn’t?”Even with shared family genetics, individual risk varies due to a combination of factors. You and your sibling might have inherited different protective or risk-enhancing genetic variants, or you may have had different exposures to environmental risk factors like alcohol, hepatitis viruses, or diet over your lifetimes.
3. I don’t drink much, but my doctor mentioned fatty liver. How?
Section titled “3. I don’t drink much, but my doctor mentioned fatty liver. How?”Fatty liver, or NAFLD, can develop even without heavy alcohol use, and genetics play a significant role. You might have inherited genetic variants that influence how your body processes fats or manages inflammation, making you more prone to fat accumulation in the liver, which can progress to more serious liver disease.
4. Does my ethnic background change my liver cancer risk?
Section titled “4. Does my ethnic background change my liver cancer risk?”Yes, your ancestral background can influence your liver cancer risk. Different populations have varying frequencies of specific genetic variants that can either increase susceptibility or offer protection, and also different prevalences of risk factors like Hepatitis B or C. This is why some populations face disproportionately higher rates.
5. Can eating healthy really prevent liver cancer if it’s in my family?
Section titled “5. Can eating healthy really prevent liver cancer if it’s in my family?”Absolutely, lifestyle choices are crucial even with a family history. While you might have a genetic predisposition, a healthy diet can help prevent conditions like nonalcoholic fatty liver disease, reduce inflammation, and support overall liver health. This can significantly lower your personal risk by counteracting some genetic vulnerabilities.
6. Why do some people get liver cancer without heavy drinking or hepatitis?
Section titled “6. Why do some people get liver cancer without heavy drinking or hepatitis?”In some cases, genetic predisposition can be a primary factor, even without common risk exposures. Individuals might carry specific genetic variations that increase their susceptibility to liver damage or cancer development through pathways related to metabolism, inflammation, or cell growth, making them vulnerable despite otherwise healthy habits.
7. Is a DNA test useful to know my personal liver cancer risk?
Section titled “7. Is a DNA test useful to know my personal liver cancer risk?”Research is ongoing, but identifying specific genetic variations can help assess your susceptibility. A DNA test could reveal variants that influence your risk of developing liver conditions like NAFLD or how your body handles certain toxins, potentially guiding personalized prevention strategies or earlier screening discussions with your doctor.
8. Does my body’s inflammation level affect my liver cancer risk?
Section titled “8. Does my body’s inflammation level affect my liver cancer risk?”Yes, chronic inflammation is a major driver of liver damage and cancer, and your genetics can influence your body’s inflammatory response. Some inherited genetic variations can make you more prone to persistent liver inflammation, which over time can lead to scarring (cirrhosis) and increase your risk for liver cancer.
9. I had Hepatitis C, but it’s treated. Am I still at high risk?
Section titled “9. I had Hepatitis C, but it’s treated. Am I still at high risk?”Even after successful treatment for Hepatitis C, some residual risk can remain, and your genetics might play a role in this. Genetic factors can influence the extent of past liver damage, how your liver heals, or your susceptibility to other liver issues, potentially affecting your long-term risk despite viral clearance.
10. My friend drinks more than me, but I worry about my liver. Why?
Section titled “10. My friend drinks more than me, but I worry about my liver. Why?”Your individual genetic makeup can influence how your liver processes alcohol and responds to damage. You might have inherited genetic variants that make your liver more vulnerable to alcohol’s effects or less efficient at repair, meaning that even moderate drinking could pose a greater risk for you compared to someone else with a different genetic profile.
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] Chalasani, N. “Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.”Gastroenterology, 2010.
[2] Wang, Y. et al. “Common 5p15.33 and 6p21.33 variants influence lung cancer risk.”Nat Genet (2008).
[3] Price, AL. et al. “Principal components analysis corrects for stratification in genome-wide association studies.” Nat Genet (2006).
[4] de Bakker, PI. et al. “Practical aspects of imputation-driven meta-analysis of genome-wide association studies.” Hum. Mol. Genet. (2008).
[5] Kiemeney, L. A. “Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.”Nat Genet., 2008.
[6] Antoniou, AC., et al. “A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.”Nat Genet.
[7] Li, Y., et al. “Genetic variants and risk of lung cancer in never smokers: a genome-wide association study.”Lancet Oncol, vol. 11, no. 4, 2011, pp. 353-360. PMID: 20304703.
[8] Romeo, S., et al. “Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.”Nat Genet, vol. 40, 2008, pp. 1461–5. PMID: 18820647.
[9] Sun, J., et al. “Sequence variants at 22q13 are associated with prostate cancer risk.”Cancer Res, vol. 69, no. 1, 2010, pp. 313-319. PMID: 19117981.
[10] McKay, JD., et al. “Lung cancer susceptibility locus at 5p15.33.”Nat Genet.
[11] Low, S. K. “Genome-wide association study of pancreatic cancer in Japanese population.”PLoS One, 2010.
[12] Murabito, J. M. “A genome-wide association study of breast and prostate cancer in the NHLBI’s Framingham Heart Study.”BMC Med Genet., 2007.