**Meet the editor**

Associate Professor Kathryn Tonissen received her Bachelor of Science with Honours (B.Sc. Hons) degree in 1986 from the University of Adelaide, South Australia. She completed her PhD in biochemistry and molecular biology at the University of Adelaide in 1991, followed by postdoctoral training at the University of Texas at Austin, USA. She is currently an Associate Professor in

the School of Biomolecular and Physical Sciences at Griffith University in Brisbane, Australia and a member of the Eskitis Institute for Cell and Molecular Therapies, also based at Griffith University. Her research is focussed on the cellular and molecular aspects of redox control, with a particular emphasis on cancer research and she has published more than 30 papers in international journals.

Contents

**Preface IX** 

**Section 1 Cancer Pre-Disposition and Pre-Cancerous** 

Chapter 1 **Synergistic Effects of Low-Risk Variant** 

**in Oral Leukoplakias 25** 

Andrés Castillo

Chapter 4 **Oestrogens, Xenoestrogens** 

**in Human Cancer 87** 

**– Potential Tumor Marker – From Protein to cDNA** 

**Alleles in Cancer Predisposition 3**  Francesca Duraturo, Raffaella Liccardo,

Chapter 2 **Binary System of Grading Epithelial Dysplasia** 

**Section 2 Cancer Development and Progression 43** 

Chapter 3 **Human Papillomavirus and Carcinogenesis** 

**in the Upper Aero-Digestive Tract 45** 

**and Hormone-Dependent Cancers 63**  Anna Ptak and Ewa Lucja Gregoraszczuk

Chapter 5 **EPS8, an Adaptor Protein Acts as an Oncoprotein** 

Chapter 6 *FJ194940.1* **Gene and Its Protein Product ACJ04040.1** 

Malwina Bartczak-Tomczyk and Marek Mirowski

**and Chromosomal Localization 105**  Ewa Balcerczak, Aleksandra Sałagacka,

Ming-Chei Maa and Tzeng-Horng Leu

Angela Cavallo, Marina De Rosa and Paola Izzo

Maria Auxiliadora Vieira do Carmo and Patrícia Carlos Caldeira

**Risk Classification 1** 

## Contents

### **Preface XI**


X Contents


## Preface

An increased understanding of the molecular, biochemical and cellular processes governing carcinogenesis can only be of benefit in improving the effectiveness of strategies used to prevent and treat cancer. Since cancer is a multifaceted and complex disease a number of factors can contribute to its development and progression. A broad knowledge of these factors may aid in understanding how they interact and influence the processes of initiating and promoting cancer. This in turn enables more effective preventative and therapeutic strategies to be devised and more relevant prognostic tools to be developed. This book includes comprehensive reviews and some specialized experimental findings that cover diverse processes that contribute to carcinogenesis, its diagnosis and treatment. The goal is for these examples to inform and influence a reader's own specialty by stimulating thinking across a diverse range of topics. A cross fertilization of ideas arising from understanding the various preventative, diagnostic and therapeutic approaches together with a broad knowledge of factors that affect cancer progression could be the impetus for further progress in tackling a disease that still exerts a heavy human toll worldwide.

Section 1 includes genetic, molecular and morphological approaches to assessing cancer susceptibility and classifying the risk of developing a cancer. While individual mutations are known to influence cancer formation a knowledge of the synergistic effects of low-risk variant alleles are also important when assessing predisposition to cancer. This section also describes a binary system using morphology and molecular analysis for classifying pre-cancerous lesions into either high or low-risk potential to subsequently develop into oral carcinoma.

Section 2 contains chapters that discuss the various mechanisms and stimuli that may contribute to the initiation of cancer or influence progression of the disease into a metastatic state. These stimuli include infection by the human papillomavirus and hormonal stimuli such as oestrogens. Specific proteins may also play a role in carcinogenesis and therefore have prognostic or therapeutic value. Examples of oncogenes and tumor markers, along with their characterisation in cancer cells, are described in this book. The oxygen environment of a cancer cell is an important determinant of carcinogenesis and a description of the redox and hypoxic signaling pathways and how they influence cancer development and metastasis is provided. The cancer microenvironment also plays a role in cancer progression and is the focus

#### X Preface

of a chapter that assesses the expression of specific stromal proteins in cancer tissues. Metastasis involves the movement of tumor cells to a distant tissue and the process of epithelial-mesenchymal transition (EMT) is described in detail in the final chapter of this section.

The study of cancer and how it develops, progresses and responds to treatments or chemopreventive agents is often conducted in animal models. Section 3 contains chapters that describe specialized models for studying cancers and offer key insights into interpreting and adapting animal studies into human consequences.

Natural products are increasingly becoming recognised as an important tool for both preventing and treating cancer. Section 4 contains chapters describing naturally sourced compounds, including dietary polyphenols, and their characterisation as chemopreventive or therapeutic agents.

This book is aimed towards researchers, students and medical practitioners wishing to obtain knowledge of the processes that underpin the broader carcinogenesis field. The goal is to inspire new ideas and innovative research directions, so that ultimately cancer will be defeated. The contributions by each of the specialist authors for their chapters and by Professor Krystyna Frenkel for the initial concept and reviews, together with the assistance from the extremely professional staff at InTech is greatly valued and appreciated in preparing this book.

### **Associate Professor Kathryn Tonissen**

School of Biomolecular and Physical Sciences and Eskitis Institute for Cell and Molecular Therapies Griffith University Nathan, Qld Brisbane Australia

X Preface

this section.

of a chapter that assesses the expression of specific stromal proteins in cancer tissues. Metastasis involves the movement of tumor cells to a distant tissue and the process of epithelial-mesenchymal transition (EMT) is described in detail in the final chapter of

The study of cancer and how it develops, progresses and responds to treatments or chemopreventive agents is often conducted in animal models. Section 3 contains chapters that describe specialized models for studying cancers and offer key insights

Natural products are increasingly becoming recognised as an important tool for both preventing and treating cancer. Section 4 contains chapters describing naturally sourced compounds, including dietary polyphenols, and their characterisation as

This book is aimed towards researchers, students and medical practitioners wishing to obtain knowledge of the processes that underpin the broader carcinogenesis field. The goal is to inspire new ideas and innovative research directions, so that ultimately cancer will be defeated. The contributions by each of the specialist authors for their chapters and by Professor Krystyna Frenkel for the initial concept and reviews, together with the assistance from the extremely professional staff at InTech is greatly

**Associate Professor Kathryn Tonissen** 

Griffith University Nathan, Qld Brisbane Australia

School of Biomolecular and Physical Sciences and Eskitis Institute for Cell and Molecular Therapies

into interpreting and adapting animal studies into human consequences.

chemopreventive or therapeutic agents.

valued and appreciated in preparing this book.

**Section 1** 

**Cancer Pre-Disposition and Pre-Cancerous** 

**Risk Classification** 

**Cancer Pre-Disposition and Pre-Cancerous Risk Classification** 

**Chapter 1** 

© 2013 Izzo et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Synergistic Effects of Low-Risk Variant** 

It has long been known that cancer can be the result of a genetic predisposition. About 5% of total cancers are associated with known Mendelian susceptibility; in these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance usually at least of 70%. However, there are many tumors in which the cause of hereditary predisposition can not be explained as the Mendelian syndromes. For colorectal cancer (CRC), for example, about 30% of cases are thought to be due to inherited susceptibility, which only in part can be explained by the known Mendelian inheritance, as FAP, MAP and Lynch syndrome [1]. Breast cancer has a similar gap between Mendelian and overall genetic risk. For prostate cancer, the risk is even higher, as very few cases are attributable to highrisk alleles. This gap needs to be filled by studies to identify predisposition alleles that explain the cases of hereditary tumors for which no association with gene variants has been

With the advent of high-throughput technology it is now possible to analyze a great number of polymorphic variants in large cohorts of cases and controls. These studies have been used successfully by many groups leading to the identification of a large number of rare variant alleles in patients with an inherited risk of cancer [3, 4]. The simultaneous presence of rare genetic variants in the same patient might contribute in a cooperative manner to increase the risk of tumor development. Another problem is represented by variants of unknown significance (VUSs) within the cancer predisposition highly penetrant genes. These variants are usually missense or silent changes which are generally rather uncommon or rare and thus of doubtful clinical relevance, that make troublesome the genetic counseling for these cancer families. The interpretation of these variations is not easy and requires the combination of different analytical strategies to get a proper assessment of their

**Alleles in Cancer Predisposition** 

Angela Cavallo, Marina De Rosa and Paola Izzo

Additional information is available at the end of the chapter

Francesca Duraturo, Raffaella Liccardo,

http://dx.doi.org/10.5772/55417

**1. Introduction** 

found, so far [2].

### **Chapter 1**
