Clinical Relevance of Genetic Factors in Pulmonary Diseases

340 Pages·2018·8.311 MB·English

by  Takeshi Kaneko

Respiratory Disease Series:
Diagnostic Tools and Disease Managements
Series Editors: Hiroyuki Nakamura · Kazutetsu Aoshiba
Takeshi Kaneko E ditor
Clinical
Relevance of
Genetic Factors
in Pulmonary
Diseases
Respiratory Disease Series: Diagnostic Tools
and Disease Managements
Series Editors:
Hiroyuki Nakamura
Ibaraki Medical Center
Tokyo Medical University
Ibaraki, Japan
Kazutetsu Aoshiba
Ibaraki Medical Center
Tokyo Medical University
Ibaraki, Japan
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Takeshi Kaneko
Editor
Clinical Relevance
of Genetic Factors in
Pulmonary Diseases
Editor
Takeshi Kaneko
Yokohama City University
Yokohama, Kanagawa, Japan
ISSN 2509-5552 ISSN 2509-5560 (electronic)
Respiratory Disease Series: Diagnostic Tools and Disease Managements
ISBN 978-981-10-8143-9 ISBN 978-981-10-8144-6 (eBook)
https://doi.org/10.1007/978-981-10-8144-6
Library of Congress Control Number: 2018948729
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Preface
Cystic fibrosis, a monogenic hereditary disease that manifests in the lungs, is well
known in Western countries and mainly affects Caucasians of Northern European
descent, but is rarely seen in Asian populations. However, polygenic hereditary dis-
eases of the lungs are commonly seen across all ethnicities, since most pulmonary
diseases are thought to result from interactions between multiple genetic and envi-
ronmental factors.
For example, chronic obstructive lung disease (COPD) is a common pulmonary
disease and cigarette smoking is the main environmental risk factor for developing
the disease. Since only approximately 15% of smokers develop COPD, genetic fac-
tors are considered to be important for the development of the disease. In fact, more
than 100 genes that affect susceptibility to non-hereditary COPD have been reported
to date, and each identified gene can explain only a small part of the etiology of
COPD. In COPD, genetic factors only become important when environmental fac-
tors exist. In contrast, in bronchial asthma, genetic factors are more important than
environmental factors. Consequently, bronchial asthma has a very high heritability
rate, reportedly as high as 70%. Many genes have been identified that are possibly
involved in the susceptibility, activity, and severity of bronchial asthma. These two
diseases demonstrate how the contribution of genetic factors varies widely depend-
ing on the disease. In this book, we discuss the contribution of genetic factors to
common pulmonary diseases that are encountered in daily practice.
The Human Genome Project was finished in 2003 and provided a complete and
accurate sequence of the 3 billion DNA base pairs that make up the human genome.
We are currently in an era of rapidly expanding knowledge about genetic medicine.
It has become possible to determine the genetic contributions to common pulmo-
nary diseases. Understanding the functions of genetic factors in each disease can
contribute significantly to various fields of medicine and enable us to identify geno-
types or phenotypes of each disease. Based on this information, new therapeutic
strategies are being developed, leading to precision medicine. By translating
genomic information into clinical practice, we can expect to minimize adverse
events and obtain the maximum treatment effect.
v
vi Preface
Striking progress has been made recently in the treatment of various cancers,
including lung cancer. Recent findings of oncogenic driver mutations resulted in a
major paradigm shift in the management of non-small cell lung cancer (NSCLC).
Treatment for this disease now focuses on a genetic biomarker-based strategy to
develop personalized treatment with molecularly targeted agents. Indeed, the prog-
nosis of NSCLC patients given treatments that are personalized based on their iden-
tified oncogenic driver mutations has dramatically improved, and their quality of
life is significantly better.
To the best of my knowledge, there is currently no textbook that focuses on the
roles that genetic factors play in pulmonary diseases. I am convinced that this book
is very unique, not only in its discussion of gene abnormality in pulmonary diseases
but also in its focus on applying cutting-edge discoveries in genetic medicine to
daily clinical practice.
I hope that this book will improve our understanding of pulmonary diseases and
lead to more appropriate treatment.
Yokohama, Japan Takeshi Kaneko
Contents
Part I Introduction
1 Clinical Development of Genomic Medicine in Pulmonary Diseases:
Are Genetic Factors Enough to Determine the Phenotype
and Inheritance of Pulmonary Diseases? . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Mari Hikichi, Shuichiro Maruoka, and Shu Hashimoto
2 Approaches to Understanding the Genetic Basis of Complex Diseases:
Overview—What Is the Rationale for the Genome-Wide Approach
to Understand Complex Diseases, Its Application and Limitations . . . . 15
Mayumi Tamari and Tomomitsu Hirota
Part II G enetic Disorders in Pulmonary Disease
3 Bronchial Asthma: Is Asthma Inherited? . . . . . . . . . . . . . . . . . . . . . . . . . 39
Nobuyuki Hizawa
4 COPD: Hereditary (A1-AT) and Non- hereditary—What Are
the Roles of Genetic Factors in the Pathogenesis of COPD? . . . . . . . . . 57
Nobuyuki Horita
5 Smoking Behavior and Cessation (Nicotine Addiction):
Are Genetic Factors Involved in Smoking Behavior? . . . . . . . . . . . . . . . 77
Tetsuya Kubota and Akihito Yokoyama
6 Cystic Fibrosis, Primary Ciliary Dyskinesia, and Diffuse
Panbronchiolitis: Hereditary and Non-hereditary—What Are the 
Roles of Genetic Factors in the Pathogenesis of These Diseases? . . . . . . 93
Masaharu Shinkai
vii
viii Contents
7 Pulmonary Fibrosis: Hereditary and Non-hereditary—What
Are the Role of Genetic Factors in the Pathogenesis
of Pulmonary Fibrosis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Takafumi Suda
8 Other Diffuse Lung Diseases: Diffuse Cystic Lung Diseases
(LAM, TSC, BHD), Sarcoidosis, Pulmonary Alveolar Proteinosis,
and Pulmonary Alveolar Microlithiasis—What Are the Roles
of Genetic Factors in the Pathogenesis of These Diseases? . . . . . . . . . . 135
Haruhiko Furusawa, Masahiro Masuo, Yoshihisa Nukui,
Yasunari Miyazaki, and Naohiko Inase
9 Pulmonary Vascular Diseases: Pulmonary Hypertension and HHT—
What Are the Roles of Genetic Factors in the Pathogenesis
of Pulmonary Vascular Diseases? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Toshihiko Sugiura and Koichiro Tatsumi
10 Mycobacterial Infection: TB and NTM—What Are the Roles
of Genetic Factors in the Pathogenesis of Mycobacterial Infection? . . 169
Kazuko Yamamoto and Hiroshi Mukae
11 Pulmonary Malignancies (1): Lung Cancer—What Are
the Roles of Genetic Factors in Lung Cancer Pathogenesis? . . . . . . . . 193
Naozumi Hashimoto, Mitsuo Sato, and Yoshinori Hasegawa
12 Pulmonary Malignancies (2): Mesothelioma—What Are the Roles
of Genetic Factors in the Pathogenesis of Mesothelioma? . . . . . . . . . . 207
Takashi Nakano, Eisuke Shibata, Kozo Kuribayashi,
Yoshie Yoshikawa, and Masaki Ohmuraya
13 Genetic Factors in Sleep Disorders: What Are the Roles
of Genetic Factors in the Pathogenesis of Sleep Disorders? . . . . . . . . . 225
Kiminobu Tanizawa and Kazuo Chin
14 Pharmacokinetics, Pharmacodynamics, and Toxicities:
What Should We Know About Genetic Factors that Affect
the Pharmacotherapy of Pulmonary Diseases? . . . . . . . . . . . . . . . . . . . 255
Takashi Sato
Part III Oncogenic Driver Mutation (Somatic Mutations) in Lung Cancer
15 EGFR: How Important Is EGFR Mutation Status
in the Management of Lung Cancer? . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Mizuki Haraguchi and Kazuhisa Takahashi
16 ALK and Others: How Important Are ALK and Other
Mutations in the Management of Lung Cancer? . . . . . . . . . . . . . . . . . . 295
Hisatsugu Goto and Yasuhiko Nishioka
Contents ix
Part IV Current Topics
17 Application of High-Throughput Technologies in Personal
Genomics: How Is the Progress in Personal Genome Service? . . . . . . 319
Kaoru Mogushi, Yasuhiro Murakawa, and Hideya Kawaji
18 Nucleic Acid Amplification-Based Diagnostics for Pulmonary Diseases:
What Is the Current State and Perspectives of Nucleic Acid
Amplification Technologies Used in Diagnostics Associated
with Pulmonary Diseases? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Oleg Gusev, Yoshihide Hayashizaki, and Kengo Usui