Genetic susceptibility to lung cancer

Haruhiko Sugimura¹, Hong Tao,¹ Masaya Suzuki¹, Hiroki Mori¹, Masaru Tsuboi¹, Shun Matsuura², Masanori Goto¹, Kazuya Shinmura¹, Takachika Ozawa³, Fumihiko Tanioka⁴, Naomi Sato⁵, Yoshitaka Matsushima⁶, Shinji Kageyama¹, Kazuhito Funai⁷, Pei-Hsin Chou⁸, Tomonari Matsuda⁸

1Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan, ²Department of Pulmonary Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku,Hamamatsu, Shizuoka, 431-3192, Japan, ³Department of Pathology, Hamamatsu Medical Center, 328 Tomizuka-cho, Naka-ku, Hamamatsu, Shizuoka, 432-8580, Japan, ⁴Department of Pathology and Laboratory Medicine, Iwata City Hospital, 512-3 Okubo, Iwata, Shizuoka, 438-8550, Japan, ⁵Department of Clinical Nursing, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku,Hamamatsu, Shizuoka, 431-3192, Japan, ⁶Department of Chemistry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku,Hamamatsu, Shizuoka, 431-3192, Japan, ⁷Department of Thoracic Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan, ⁸Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Otsu, Shiga, 520-0811, Japan

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Candidate genes of lung cancer susceptibility

3.1. Carcinogen-activation genes

3.2. Carcinogen-detoxification genes

3.3. Repair gene polymorphism and lung cancer susceptibility　

3.4. Oncogene and suppressor gene polymorphisms, and other genetic and epigenetic variations to modify lung Cancer susceptibility

4. The Era of genome-wide association study

5. Smoking behavior and lung cancer susceptibility

6. Exposure assessment and lung cancer susceptibility

7. Perspectives

8. Acknowledgements

9. References

1. ABSTRACT

Lung cancer is a highly environmental disease, but cancer researchers have long been interested in investigating genetic susceptibility to lung cancer. This paper is a historical review and provides updated perspectives on lung cancer susceptibility research. The recent introduction of easier genotyping methods and the availability of an almost complete human genome database facilitated the association study to thousands of cases and controls for millions of genetic markers. Discoveries in the field of behavior genetics, that is, the genetic aspects of smoking behavior and nicotine addiction, unexpectedly indicated that polymorphisms in the human central nervous system play an important role in eventually leading to lung cancer. These findings were achieved by using comprehensive approaches, such as a genome, transcriptome, or proteome approach, and the studies were often conducted without a hypothesis. Another-omics approach, the "adductome" or "exposome" approach to how life style information can be integrated into the framework of genetic association studies, has recently emerged. These new paradigms will influence the area of lung cancer risk evaluation in genome cohort studies. [Frontiers in Bioscience 14, 2009-2009, January 1, 2009]

[Frontiers in Bioscience 14, 2009-2009, January 1, 2009]

Alternatively spliced tissue factor pathway inhibitor: Functional Implications Alan E. Mast1 1Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Alternatively spliced forms of TFPI 4. Evolution of alternatively spliced forms of TFPI 5. Tissue expression of alternatively spliced forms of TFPI 6. Perspective: Potential for differential function of alternatively spliced forms of TFPI 7. References 1. ABSTRACT Tissue factor pathway inhibitor (TFPI) is a factor Xa dependent inhibitor of tissue factor initiated blood coagulation. In recent years several alternatively spliced forms of TFPI have been identified. These alternatively spliced forms have different C-terminal regions and have different mechanisms for association with cell surfaces. They are differentially expressed in human and mouse tissues and may have distinct physiological functions.