Contents

Serial No. Title Page No.

1 INTRODUCTION 1

2 REVIEW OF LITERATURE 7

3 MATERIAL AND METHODS 12

6 LITERATURE CITED 24

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CHAPTER 1

INTRODUCTION

Cancer is a group of diseases that involve in abnormal cell division, with the latent to
extent the other parts of the body. Due to this abnormal cell division tumors are formed which
are classified into two basic categories. Benign tumor and malignant tumor. benign tumors are
not classified as being cancer because they do not spread to other parts of the body,while
malignant tumor attach to other body parts and cause different diseases.There are over 100
different known cancers that affect humans.(National cancer institute.2014).
Cancers forms are classified on the basis of their origon and type of cell from tumor
originate. These types include, Carcinoma, it include lung, breast, pancreas prostate and colon
cancer. Sarcoma, Cancers ascending from connective tissue. There are msenchymal cells
present out side the bone marrow, both carcinoma and sarcoma types develop from these cells.
Lymphoma and leukemia are types of cancer originating from blood making cells. Germ cell
tumor, Cancers from pluripotent cells,these cells present in the testicle(seminoma) or the ovary(
dysgerminoma). Blastoma, Cancers consequent from immature embryonic
tissue(Claudette,2014).
Malignant tumor cells prerequisite a blood supply adequate to stand for development and
fast growth, during the alteration of a tumor from a benign to a malignant form. The tumor
thickness is not as much of 2 mm and there are no vessels in the tumor tissue during its early
growth stage. Therefore, the supply ofoxygen and nutrient to the tumor is chiefly hooked on
diffusion from adjoining tissues. Following growth in tumor size , tumor cells obtain oxygen as
well as nutrients by angiogenesis. Angiogenesis is a vigorous process for tumor growth and
development, which is required for blood stock from the universal circulation, relating the
growth of novel blood vessels from pre-standing vessels. It also happens in the course of wound
curing and in granulation flesh ( Zhang et al. 2016b).
The name of cancer usually assigned by the suffix -carcinoma, -sarcoma or –blastoma,
name of organ from which they are originate. For example, hepatocarcinoma, a name of cancer
form given on the base of arising malignant epithelial cells of parenchyma, while a tumor arising
from embryonic liver pioneer cells is known as hepatoblastoma, and a cancer originating from

1
fat cells is called a liposarcoma. There are an English organ name are used In case of some
common cancers . For example, the utmost communal form of breast cancer is called ductal
carcinoma of the breast. Here, the word ductal refers to that it has originated in the milk ducts of
breast.
There are many forms of cancer that are most prevailing in world wide, lung cancer,
breast cancer, colorectal cancer, cervicel cancer, prostate cancer, skin cancer, liver cancer, brain
cancer, stomach cancer, blood cancer.
In case of Lung cancer the uninhibited growth of irregular cells occur in the cells that
mark the air passages. Molecular studies make sure that genetic connections, across unlike
verticals, principal to mutations and variations are few of the common aspects responsible for
multi-locus and multifactorial diseases such as lung cancer (A.R.hsieh et al 2011). Yet,
sequencing studies have found nil mutations in the genes of many tumor models (Mack et al.,
2014;). Whole genome and whole-exome sequencing of 47 ependymomas visible an extremely
small mutation rate, with zero significant recurring nucleotide variations (Mack et al., 2014;
Versteeg, 2014).
It is showing from experimental data numerous non-mutagenic aspects effect the cancer
risk and growth. Human studies designate that the hormone therapy cause the increment of
cancer risk. Air pollution, which is combination of traffic-related air pollution as well as
discharges of industries effect the ozon level. With the addition of chemical mutagens such as
benzene, particals and metels and possible ozon have hazardous potential (Morch et al.,2009). A
complex frame of risk influences such as environmental contamination, tobacco/cigarette smoke,
oxidizing agents, alkylating mediators together with the genetic variability slopes an individual
to the risk of lung cancer. Tobacco usage is the first-born and most well-reputable risk factor
towards lung cancer (Groot and Munden.,2012).
Breast cancer(BR) is uncontrolled development of malicious cells in the mammary
epithelial tissue. The disease occur in both genders. Breast cancer is the most common type of
cancer in female worldwide, with the frequency that increases intensely with age. Breast cancer
apparently accounted for 29% of all cancer cases and 14% of all cancer-related deaths among
female in worldwide up to 2012 (Siegel et al.,2013) .

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 Risk factors for BR in the female population, is increases with the age of mother at the
time of first child birth, declines in the size of family, increases in post-menopausal fatness,
increases with the alcohol usage. In the middle of the night physiologic relief of the melatonin
hormone is changed by environmental lighting that reduce the production of melatonin.The
reduction in melatonin hormone production estrogen level increase which stimulate hormone-
sensitive tumors of breast. ( Czeisler and Dijk, 2001).
Other groups have projected that the rise in light contact decreases the amount of time
obtainable for melatonin manufacturation, which decreases the possible generic oncostatic
outcome of the pineal gland, thus increasing the BR risk ( Kerenyi et al., 2001).
Colorectal cancer (CRC), also recognized as colon cancer, is the expansion of cancer
from the colon or rectum (parts of the large intestine).
CRC are due genetic disorders but in rare cases it occur due to life style and old age.
Some risk factors contain smoking, lack of physical activity, obesity and diet. Consumption of
alcohol as well as red and processed meat. Another risk influence is provocative bowel disease,
that includes Crohn's disease and ulcerative colitis. Adenomatous polyposis and hereditary non-
polyposis examples of CR are due to hereditary genetic syndromes. It started as a benign cancer
and with the passage of time becomes cancerous (National Cancer Institute,2014).
Cervical cancer(CC )is a cancer originating in the cervix. Human papillomavirus
infection (HPV) is cause 91% of cases. Additional risk factors are weak immune system,
starting sex at early age, birth regulator medicines, smoking and have several sexual partners.
About 90% of CC occur in squamous cell, 10% are adenocarcinoma.
In case of brain , cancer cells develop to formulat a frame of cancer tumor.The normal
body functions such muscle regulator, perception, retention are highly effected by these cancer
tumors. (National Brain Tumor society,2013). Risk factors of BC include alcohol and tobacco
use, certain chemicals, lack of physical activity, diet, exposure to ionization and other life style.
However, BC occur due to some heriditory and genetic fectors in 6-11 %age. In hereditary brain
cancer, mutation, which cause the formation of specific genea is transfer from grandfather to
child( American Brain Tumor Association.2014).
Most genetic dissorders occur with the passage of time or with age. Mutation occure on
chromosome number 1, 10, 13, 17, 19, and 22. In case of oligodendrogliomas changes occure on

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chromosomes 1 and 19. meningiomas are due to changes on chromosome 22. ( Dorsey et
al.,2014).
Blood cancers effect the production and function of your blood cells. Blood cancer start
in bone marrow. Stem cells in bone marrow grow into three types of cells: erythrocytes,
leukocytes and platelets. In most blood cancers, the normal blood cell development process is
intermittent by uncontrolled development of an irregular kind of blood cell. These uncontrolled
cell division in blood cells inhibited blood to achieve numerous functions, like hostile off
toxicities or avoiding intense bleeding. Leukemia is 30% of all of the disease that mostly infect
the children However, in adults lymphoma as well as leukemia is common.
There are three main types of blood cancers. Leukemia, in this situation leukocytes grow
abnormally and there number is largely increase. The leukocytes are not completely grow and
called leukemia cells (National Cancer Institute.2014).
Genetic and environmental factors play important role. Factors that cause leukemia are
include smoldering, chemicals, ionizing emission, Down syndrome and previous chemotherapy
Individuals with intimate times past of leukemia also have high risk. The types of leukemia are -
acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic
leukemia (CLL) and chronic myeloid leukemia (CML). ( Leuke Cătoi, Alecsandru Ioan
Baba,2017).In caase of Lymphoma lymphatic system is effected which eliminates extra fluids
from physique and product is immune cells. These Lymphocytes are afight with infection.
Irregular lymphocytes convert lymphoma cells, which accumulate in lymph lumps. Myeloma is
type of cancer of the plasma cells. Researchers at the Wellcome Trust Sanger Institute identified
the SF3B1 gene as being frequently mutated in myelodysplasia, one of the most common forms
of blood cancer. ( Hutter,2010).

Skin cancer (SC) occur in cells of skin. There are 3 main types of skin cancers, Basal cell
skin cancers, Melanomas, Squamous cell skin cancers. Additional skin cancers include Kaposi
sarcoma Cutaneous lymphoma, Merkel cell carcinoma, Skin adnexal cancers, Numerous kinds of
malignancies, all these types interpretation for less than 1% of SC. The chief risk influence for
melanoma as well as non-melanoma cancers is revelation to UV ultraviolet light comprising
daylight and burning cradles, risk rising as the amount of exposure increase. Smoking, cause
squamous cell skin cancers, especially on the lips. Chemical contact counting arsenic,

4
manufacturing tar, petroleum, paraffin and oil, rise the risk of non-melanoma skin cancers
(Siavash et al.,2009).
The factors that cause SC including age, as the age increase risk SC also increase, gender,
Males are nearly double times more expected to grow basal cell carcinomas and three times are
expected to grow squamous cell carcinomas as compared to female, Skin tone. Those with one or
both parents or relatives SC have high risk. The skin’s skill to renovation UV damage is effected
by xeroderma pigmentosum Condition that is inherited to individuals and this risk is develop at
early age. Viruse, human papilloma virus (HPV) taints affect the genital part that rise the hazard
of SC(American Cancer Society,2017).
Proliferation of cells in prostate gland is known as prostate cancer (PC). In the male
reproductive system prostate is a gland that produce semen which transports sperm. The walnut-
sized of tube that carries urine from the bladder is located in the higher part of the urethra below
the bladder. Age is the major factors that cause PC is erratic in men at the age of forty-five years
and universal at the fifty years old.(Parkin et al.,2013).
Geography, PC arises more regularly in Australia, northwestern Europe, North America
and in the Caribbean islands. But the reason behind the PC is remain indistinguishable. Genetic
factors and certain indigenous factors cause the PC. It is a heriditory disease which transfer from
parents to offspring as well as if the person has identical twins chance of PC is increase
(National Comprehensive Cancer Network, 2016).
Irregular cell division in the liver cause Liver cancer ( LC). The most common type of
LC is hepatocellular carcinoma that start in hepatocyte cells. Other types of LC are
hepatoblastoma as well as intrahepatic cholangio carcinoma. ( Böhmer et al., 2016).
Risk factors that enhance the LC comprise of Prolonged contagion with HBV, HCV
hepatitis B virus (HBV), hepatitis C virus (HCV) respectively. Cirrhosis is a condition in which
scar tissue are produce that enhance the chance of LC. Hemochromatosis as well as Wilson's
disease are inherited cause LC. ( Feldman M et al., 2016).The patients of diabetes have great
chance of LC. Increase of fat in the liver increases the possibility of liver cancer. Toxins
produced by sorts that grow on crops such as peanuts which become aflatoxin which are very
polluted. When alcohol use in large amount it leads to LC (Rochester., 2015).
Cancer produce from esophagus contamination also called esophageal cancer
(EC).Gastroesophageal confluence is most common example of EC. Almost ninety percent of

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EC are squamous-cell carcinomas and adenocarcinomas. On rare cases, melanomas,
leiomyosarcomas, lymphomas, carcinoids also exampels of EC.
Gastric cancer (GC) is cancer emerging from the coating of the stomach. Helicobacter
pylori bacterium is major cause of GC which interprete about 60% of cases. other risk factors of
GC are pickled vegetables, obesity and smoking (González et al.,2013). CDH1 gene is a genetic
imperfection which is a genetic risk. For example hereditary diffuse gastric cancer (HDGC).
CDH1 gene programs for E-cadherin, present on chromosome number sixteenth. By the
involvement of this gene in a specific mutation GC occur. This mutation is measured as
autosomal leading sense that half of a carrier’s children will be involve(Hereditary Diffuse
cancer institute,2014).

OBJECTIVE: The report is formulated to estimate the most prevailing form of cancer in all the
word.

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 Charter 2

REVIEW OF LITERATURE

Hubbard et al. (2000) evaluated the general population that based on group study about
890 subjects with cryptogenic fibrosing alveolitis. And 5,884 control subjects drawn from the
United Kingdom General Practice Research Database. That increase in lung cancer incidence
remained when the analysis was restricted to current smokers (RR 7.36, 95% CI 1.54 to 35.19, p
= 0.012). At the end result provided clear evidence that the incidence of lung cancer is increased
in patients with cryptogenic fibrosing alveolitis, and that this effect is independent of the effect
of cigarette smoking. Lung cancer and cryptogenic fibrosing alveolitis, a population-based group
study.
DeSantis, C. et al. (2014) studied that American Cancer Society provides an overview of
female breast cancer statistics in the United States, including data on incidence, mortality,
survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620
breast cancer deaths are expected to occur among US women in 2013. Incidence rates increased
for estrogen receptor‐positive breast cancers in the youngest white women, Hispanic women
aged 60 years to 69 years, and all but the oldest African American women. These divergent
trends may reflected etiologic heterogeneity with different factors, like obesity and parity on risk
by tumor. Continued progress in the control of breast cancer will require sustained and increased
efforts to provide high‐quality screening, diagnosis, and treatment to all segments of the
population.
Key, T. JB et al. (2001) studied that breast cancer is the commonest cause of cancer
death in women worldwide. Rates vary about five-fold around the world, but they are increasing
in regions that until recently had low rates of the disease. Many of the established risk factors are
linked to oestrogens. Childbearing reduces risk, with greater protection for early first birth and a
larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives
and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears
to diminish once use stops. Alcohol increases risk, whereas physical activity is probably
protective. Mutations in certain genes greatly increase breastcancer risk, but these account for a
minority of cases.

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 Giulio Genovese et al. (2014) Clonal hematopoiesis with somatic mutations was observed
in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of
age. Detectable clonal expansions most frequently involved somatic mutations in three genes
(DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers.
Analysis of bone marrow–biopsy specimens obtained from two patients at the time of diagnosis
of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Clonal
hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is
increasingly common as people age, and is associated with increased risks of hematologic cancer
and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently
mutated in apparently healthy persons; these mutations may represent characteristic early events
in the development of hematologic cancers.
Arbyan et al.(2008) estimated 530 000 cases of cervical cancer and 275 000 deaths from
the disease in 2008. It is the third most common female cancer ranking after breast (1.38 million
cases) and colorectal cancer (0.57 million cases). The incidence of cervical cancer varies widely
among countries with world age-standardised rates ranging from <1 to >50 per 100 000. Cervical
cancer is the leading cause of cancer-related death among women in Eastern, Western and
Middle Africa; Central America.
Fearon et al. (2011) studied to develop a framework for the definition and classification
of cancer cachexia a panel of experts participated in a formal consensus process, including focus
groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome
defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot
be fully reversed by conventional nutritional support and leads to progressive functional
impairment. Its pathophysiology is characterised by a negative protein and energy balance driven
by a variable combination of reduced food intake and abnormal metabolism. The agreed
diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2%
in individuals already showing depletion according to current bodyweight and height (body-mass
index [BMI] <20 kg/m2) or skeletal muscle mass (sarcopenia). Assessment for classification and
clinical management should include the following domains: anorexia or reduced food intake,
catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus
exists on a framework for the definition and classification of cancer cachexia.

8
 Parsonnet, J et al. (1993)Gastric cancer remains among the leading types of cancer
worldwide. There is now convincing evidence linking H. pylori to adenocarcinomas of the
gastric antrum, body, and fundus. These tumors are rapidly decreasing in incidence in the United
States, whereas cardia tumors, tumors unassociated with H. pylori infection, are on the increase.
Although criteria for causality have not been completely fulfilled for H. pylori and
adenocarcinoma, there are plausible mechanisms by which chronic inflammation could induce
carcinogenesis ("mitosis causes mutagenesis"). Because gastric cancer is unusual in the United
States, screening and treatment of H. pylori in the general population are unwarranted.
Chemoprevention in high-risk populations, however, could potentially be used to decrease risk
for adenocarcinomas distal to the cardia.
Rugge, M. et al. (2015) evaluated The incidence and mortality of gastric cancer have
fallen dramatically in US and elsewhere over the past several decades. Nonetheless, gastric
cancer remains a major public health issue as the fourth most common cancer and the second
leading cause of cancer death worldwide. Demographic trends differ by tumor location and
histology. While there has been a marked decline in distal, intestinal type gastric cancers, the
incidence of proximal, diffuse type adenocarcinomas of the gastric cardia has been increasing,
particularly in the Western countries. Incidence by tumor sub-site also varies widely based on
geographic location, race, and socio-economic status. The main risk factors for distal gastric
cancer include Helicobacter pylori (H pylori) infection and dietary factors, whereas
gastroesophageal reflux disease and obesity play important roles in the development of proximal
stomach cancer. The purpose of this review is to examine the epidemiology and risk factors of
gastric cancer, and to discuss strategies for primary prevention.
Kamangar, F (1994, April) To maintain a constant red blood cell mass, therefore,
approximately 20 mL of red blood cells must be produced each day to replace those red blood
cells lost from the circulation through senescence. Anemia, which may be defined functionally as
lack of sufficient red blood cells to maintain adequate tissue oxygenation, develops when the
demand for new red blood cells exceeds the capacity of the bone marrow to produce them.
Indeed, anemia in patients with cancer appears to behave much like that in patients with chronic
renal failure who become anemic because of the inability of the kidneys to produce
erythropoietin adequately. The cause of impaired erythropoietin production in patients with
cancer who have anemia is not entirely understood, but may be due in part to the production of

9
inflammatory cytokines in response to the tumor. Such cytokines also would be expected to blunt
the ability of the bone marrow to respond to the available circulating erythropoietin.
Hashizume, H., and McDonald, D. M (2005) studied Tumor blood vessels have multiple
structural and functional abnormalities. They are unusually dynamic, and naturally undergo
sprouting, proliferation, remodeling or regression. The vessels are irregularly shaped, tortuous,
and lack the normal hierarchical arrangement of arterioles, capillaries and venules. Endothelial
cells in tumors have abnormalities in gene expression, require growth factors for survival and
have defective barrier function to plasma proteins. Pericytes on tumor vessels are also abnormal.
Aberrant endothelial cells and pericytes generate defective basement membrane. Angiogenesis
inhibitors can stop the growth of tumor vessels, prune existing vessels and normalize surviving
vessels. Loss of endothelial cells is not necessarily accompanied by simultaneous loss of
pericytes and surrounding basement membrane, which together can then provide a scaffold for
regrowth of tumor vessels. Rapid vascular regrowth reflects the ongoing drive for angiogenesis
and bizarre microenvironment in tumors that promote vascular abnormalities and thereby create
therapeutic targets.
Kamangar, F et al. (2003) studied Free radicals are ubiquitous in our body and are
generated by normal physiological processes, including aerobic metabolism and inflammatory
responses, to eliminate invading pathogenic microorganisms. Because free radicals can also
inflict cellular damage, several defences have evolved both to protect our cells from radicals —
such as antioxidant scavengers and enzymes — and to repair DNA damage. Understanding the
association between chronic inflammation and cancer provides insights into the molecular
mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as
a crucial pathway in inflammatory-mediated carcinogenesis.
Kamangar, F et al. (2009) conducted the environmental risk factors and predisposing
conditions for the two main histological types of esophageal cancer, esophageal squamous cell
carcinoma (ESCC) and esophageal adenocarcinoma (EA). Tobacco smoking, excessive alcohol
consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low
socioeconomic status increase the risk of ESCC. Results of investigations on several other
potential risk factors, including opium consumption, intake of hot drinks, eating pickled
vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic
hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are also discussed.

10
Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and probably
absence of H. pylori in the stomach increase the risk of EA. Results of studies investigating other
factors, including low intake of fresh fruits and vegetables, consumption of carbonated soft
drink, use of H2 blockers, non-steroidal anti-inflammatory drugs, and drugs that relax the lower
esophageal sphincter are also discussed.
Das, P. M Singal, R (2004) studied DNA methylation is an important regulator of gene
transcription, and its role in carcinogenesis has been a topic of considerable interest in the last
few years. Alterations in DNA methylation are common in a variety of tumors as well as in
development. Of all epigenetic modifications, hypermethylation, which represses transcription of
the promoter regions of tumor suppressor genes leading to gene silencing, has been most
extensively studied. However, global hypomethylation has also been recognized as a cause of
oncogenesis. Because DNA methylation is reversible, drugs like 5-azacytidine, decitabine, and
histone deacetylase inhibitors are being used to treat a variety of tumors. Novel demethylating
agents such as antisense DNA methyl transferase and small interference RNA are being
developed, making the field of DNA methylation wider and more exciting.

11
CHAPTER 3

MATERIAL AND METHOD

STUDY AREA

To study and estimate the most prevailing form of cancer in all over the world, I search the
different tools as;

. Science direct.

.Google, Google.

.Scholar.

.pdf reader.

.full pdf.

.science hub.

.Elsevier Science.

Using OVID, as in the meta-analysis on prevailing cancer form.

The data is collected from institute and websites;

.National Institute center.

.American society for cancer.

.World health organization.

Since 2017, instance cases of cancer in all over the world have been reported by hospital
departments, pathology laboratories and practising physicians, mainly dermatologists.

Only one skin cancer of each morphologic type is recorded most prevailing form of cancer in
New Zealand , with an indication in the register of persons with multiple skin cancers of a given

12
type located to more than one site of the body. Incidence rates are therefore based on the number
of persons with tumors rather than the number of tumors. All cases of malignant melanoma,
basal cell carcinoma and squamous cell carcinoma of the skin identify in the period January 2017
to march 2018. Rates were calculated as average annual incidence rates per 100,000 persons with
the Worldwide population on 1 march 2018 as the denominator. The incidence rates have been
age-standardized to the World Population by the direct method.

13
Table. 1 Most prevailing form of cancer in worldwide 2015.

Serial no. Type of cancer Number Frequency

1 Lungs cancer 6307 17%

2 Breast cancer 5619 15.7%
3 Colorectal 4530 13.5%
4 Prostate ( in males) 4202 11%
5 Blood cancer 5003 14%
6 Skin cancer 8703 29.1%
7 Oesophagus 950 3%
8 Brain cancer 841 3.7%
9 Gastric cancer 513 2.1%
10 Cervicle cancer ( in female) 498 2%

Chart Title
10000
8000
6000
4000
2000
0
Number Frequency

1 Lungs cancer 2 Breast cancer 3 Colorectal

4 Prostate ( in males) 5 Blood cancer 6 Skin cancer
7 Oesophagus 8 Brain cancer 9 Gastric cancer
10 Cervicle cancer ( in female)

Fig. 1 describe most prevailing form of cancer in worldwide 2015.

14
Table. 2 Most prevailing form of cancer in males worldwide 2015.

Serial no. Type of cancer in Males Number Frequency

1 Lungs cancer 2832 17.7%

2 Breast cancer 150 2%
3 Colorectal 2031 13.1%
4 Prostate 4202 11%
5 Blood cancer 2881 7%
6 Skin cancer 3442 22%
7 Oesophagus 650 4.1%
8 Brain cancer 555 2.1%
9 Gastric cancer 245 1.2%

Chart Title

4500
4000
3500
3000
2500
2000
1500
1000
500
0
Colorectal

Prostate
Breast cancer

Blood cancer

Brain cancer

Gastric cancer
Lungs cancer

Skin cancer

Oesophagus

1 2 3 4 5 6 7 8 9

Number Frequency

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Table. 3 Most prevailing form of cancer in females in worldwide 2015.

Serial no. Type of cancer Number Frequency

1 Lungs cancer 2551 15%

2 Breast cancer 5487 29.4%
3 Colorectal 1972 11%
4 Blood cancer 2351 6.1%
5 Skin cancer 6341 30%
6 Oesophagus 300 2.1%
7 Brain cancer 419 1.8%
8 Gastric cancer 254 25%
9 Cervicle cancer ( in female) 498 2%

Chart Title
7000
6000
5000
4000
3000
2000
1000
0
Colorectal

Blood cancer

Gastric cancer
Breast cancer

Brain cancer
Lungs cancer

Oesophagus
Skin cancer

Cervicle cancer ( in
female)

1 2 3 4 5 6 7 8 9

Number Frequency

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Table. 4 Malanoma incidence rates in different countries.

In different countries Male Female Both

Australia 2003 44.5 32.1 38.3

Newzealand2003-06 41.2 35.3 38.25

Belgium 56.8 23.9 45.7

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Table. 5 Age standerised skin cacer in different countries.

AGE-standardised rate per 100,000

Rank country (world)

1 Denmark 339.2

2 France 325.7

3 Australia 324.2

4 Belgium 322.2

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Table. 6 Cost of skin cancer snd related conditions .

Melanoma Non-melanoma Total

Lost life year 3,912 950 4,845

Health-care Costs $6.1mn $52.5mn $59.2mn

Lost Production $60.3mn $7.8mn $67.0mn

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 DISCUSION

From the following data it is clear that skin cancer (SC) is one of the most prevailing form of
cancer.Dr Elizabeth Baird in 2014, provides evidence on the risks of non-melanoma(NMSC)
and melanoma SC (MSC) in New Zealand associated with to another place. The rat of SC in
New Zealand is 8.2 which is high as compared to Australia 7.1. New exploration specifies that
New Zealand has now surpassed Australia as the world spearhead in offensive melanoma rates.
SC is the most common cancer in New Zealand. New SC total about 68,000 per year, compared
to a total of 16 700 for all other kinds of cancer. In fact, the incidence of melanoma in New
Zealand and Australia is about 4 (four)times sophisticated than in, UK ,US and Canada.

Melanoma cases are stated. In 2011, there remained 2304 circumstances of melanoma in New
Zealand. The more commonly effect on death is malicious melanomas (439 deaths in 2011).
MSC is most communal form in elder persons from the age limit of 26-45 years. but not known
as ‘old person’s disease’.

Richard McKenzie, gave the reason of high level of Ultra violet(UV) in New Zealand in
summer stock as compared to other hemisphere outlines three main reasons why UV levels in
New Zealand during are higher than at corresponding latitude. Over ninety percentage of skin
cancers are due to extra UV revelation in extraordinary UV situations alike New Zealand. NMSC
are mostly originate on the uncovered portions of the body. and long-term effect of UV
revelation is a major reason.

Malignant melanoma risk is related with an person’s UV contact designs and inherited
physiognomies as well as it depends upon the like unbiased skin, Bright skin form, numeral of
moles and glut sun exposure, specifically in youthful and puberty, are the chief forecasters of SC
risk. The amount of UV radiation that received by New Zealand forty percentage greater in
summer stock than at equivalent liberties in north hemisphere (NIWA research).

Ozone layer is a good absorbent for UV rays coming from sun. Any reduction in ozone layer
(such as the ‘ozone hole’ over Antarctica) is predictable to rise exterior to absorb UVB levels.
Extreme UVB contact reasons SC such as basal cell carcinomas (BCC) and squamous cell
carcinomas(SCC). Ozone layer does not riveted UVA, which is related to melanoma.

20
The significant proportion of the population that has skin types which burn easily (due to our
genetic heritage).

Followings environmental causes of skin cancer are time consuming experience to elements e,g
arsenic, oil and tar. Radiation from other cancer treatments, preceding antiquity of SC, prior skin
contagions, convinced actions for psoriasis relating UV light, definite unusual SC diseases, such
as xeroderma pigmentosum and basal cell nevus syndrome(BCNS), damaged susceptible system,
contamination by definite forms of human papilloma virus(HPV), smoldering, assured forms of
spies, existence as well as inclination to ‘pursue the sun’.

The other key risk issue is rational skin. SC is more communal in Caucasians as compared to
African-Americans. Melanin pigment which absorb less UV light and is major cause of
protection from UV light. People with rational skin that speckles or prickles certainly are at
specpesially great risk. However, all type of skin get cancer.

More than 90 types of polyps are appare on the skin some of these are familial and some are
genetic mechanisms, either in isolation or as part of a syndrome with other features.
Nonmelanoma SC which include Basal cell carcinoma (BCC) and squamous cell carcinoma
(SCC) are communal distortionsin US are frequently produced by sun revelation as well as
inherited diseases and genetic factor are also related with an enhance risk of evolving these
disease. Nonmelanoma is more common as compared to Melanoma SC.

Numerous genetic factor and inherited conditions are linked with the expansion of SC. Basal cell
nevus syndrome (BCNS), begun by pathogenic variants in PTCH1 and PTCH2) is accompanying
with an amplified risk of BCC, while conditions such as epidermolysis bullosa, oculocutaneous
albinism, xeroderma pigmentosum (XP), and Fanconi anemia are related with an improved risk
of SCC. The chief tumor suppressor genetic factor related with melanoma is CDKN2A;
pathogenic variants in CDKN2A projected to account for 36% to 40% of all known melanomas.
Pathogenic variants in many other genes, including CDK4, CDK6, BAP1, and BRCA2, have
also been found to be associated with melanoma.

Skin section showing the proliferative response induced by a tumor promoter in the epidermis of
a wild-type mouse.

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Rho GTPases, which influence gene expression, cell proliferation, and programmed cell death,
show high levels of activity in many cancers, including skin cancer. Researchers believe a family
of compounds called GDP/GDT exchange factors (GEFs) are critical to Rho GTPase activity in
tumor development and maintenance; however, because there are so many GEFs, determining
which ones are essential and what their exact roles are have been open questions. In this issue of
PLOS Biology, Mauricio Menacho-Márquez and colleagues start to provide answers. The
researchers describe studies showing that GEFs of the Vav subfamily play important roles in the
development of skin cancer tumors in mice.

To do this, the scientists worked with knockout mice deficient for Vav2 and Vav3 and also with
tissue cultures that were deficient for the two proteins. First, using wild-type and knockout mice,
the researchers used two methods involving powerful carcinogens to promote the development of
squamous cell carcinomas. In one case, mice were subjected to repeat applications of 7,12-
dimethylylben[a]antracene (DMBA). The knockout mice had a 2-fold reduction in total tumors,
indicating that the knocked out genes (Vav2 and Vav3), were important to tumor formation.
When the mice were treated with DMBA followed by 12-O-tetradecanoylphorbol-13-acetate
(TPA), the difference was even starker. The knockout mice had a 5-fold lower rate of tumors.
The knockout mice showed normal skin development, suggesting that Vav2 and Vav3 were
important for cancer formation but not necessary for normal skin development.

Additional experiments sought to explain how the Vav proteins promote tumors. Looking at the
immediate reactions to DMBA, the scientists found that the compounds caused a 2-fold increase
in programmed cell death in the knockout mice. In tissue culture, deficient keratinocytes, the
main cell type of the epidermis, also suffered higher rates of apoptosis. This fits with the lower
rates of tumor development: if the cells die, they can't become cancerous. The team also showed
that TPA has a different effect on wild-type and knockout mice; knockouts do not have the
normal proliferative and inflammatory responses to the chemical, indicating that Vav2 and Vav3
are needed for these responses and subsequent tumor formation. Importantly, this is seen even in
mice with a normal blood formation system, indicating that it's the role of Vav2 and Vav3 in the
epidermis that matters.

22
Further experiments demonstrated that Vav proteins influence intrinsic signaling programs in
skin cells. Specifically, they showed that when TPA was added to keratinocyte cell cultures,
there was reduced activation of proteins involved in cell cycle progression such as extracellular-
regulated kinase (Erk), a serine/threonine kinase, and the signal transducer and activator of
transcription (Stat3), a transcription factor. The phosphorylation levels of Erk and Stat3 could be
rescued by the re-expression of Vav2 or Vav3 in these cells, indicating that those defects were a
direct consequence of the absence of these proteins in skin cells.

Microarray experiments revealed that Vav proteins are involved in the activation of a large
biological program composed of extracellular factors that influence the behavior of epithelial
cells and their neighbors, such as inflammatory and other tumor-associated stromal cells. Co-
culturing of Vav-deficient keratinocytes in the presence of wild-type cells eliminated both their
survival and proliferative defects, indicating that Vav proteins play a critical role. This
extracellular signaling program was not conserved in the Vav2/Vav3-dependent transcriptome
that the same group has described recently in mouse breast cancer cells, supporting the idea that
this biological program is specific to the epidermal cells. By contrast, the Vav2/Vav3-dependent
gene signature was found conserved in fully developed tumors, indicating that it may also play
roles in tumor maintenance and/or progression.

Taken as a whole, these experiments indicate that Vav2 and Vav3 play important roles in the
initiation and development of skin cancers, and that they also promote longer-term changes in
cellular signaling that support cellular survival of DNA damage, with increases in proliferation
and the development of an inflammatory environment that can lead to tumor formation.

23
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