A NEW QUESTIONNAIRE FOR ORAL AND LARYNX CANCER SCREENING. INVESTIGATION AND
PRELIMANARY RESULTS ON LARYNGECTOMEES
-DUCA, MASSIMO PHYSICIAN, ENT - INST.CLINIC.PERF .BUZZI (MILANO) ITALY
PHONE 39 3392277584: MAIL ADDRESS massimoduca1@gmail.com
-MENICAGLI ROBERTO. SENIOR RESEARCHER BIOLOGICAL AND BIOCHEMISTRY
SCIENCE (MILANO) ITALY - PHONE 390290661201; MAIL ADDRESS: menicagli@libero.it
-MAROTTA ORTENSIO. PHYSICIAN DIR U.O ENT . S. Anna SAN SEBASTIAN HOSPITAL
CASERTA ITALY -PHONE 39 3396681590: MAIL ADDRESS .ortensio.marotta @ alice.it
- RANCOITA PAOLA MARIA VITTORIA;. UNIVERSITY RESEARCHER “ CENTRE FOR
BIOMEDICAL SCIENCES STATISTIC” HOSPITAL SAN RAFFAELE( MILAN ),ITALY,
PHONE 390 226 433 844. MAIL ADDRESS: rancoitapaolamaria@unisr.it
KEY WORDS:
LARYNGEAL CANCER
MUCIN
QUESTIONNAIRE
SIALIC ACID
AUTOIMMUNE DISEASE
Page 2
ABSTRACT
The aim of this work was to verify the application of a new anamnestic questionnaire , also with
the possibility of self-evaluation, for preliminary screening in the identification of possible cancer
of the oral cavity and larynx.
-For the oral cavity and larynx there are not effective methods of screening for early detection of
cancer, there are not criteria for self-evaluation, detectable with questionnaires, as is the case for
example for cardiovascular disease, lacking both the identification of almost all risk factors, both
biological structure their main target. From this analysis of are proposed ten specific risk factors,
and their main target was found in the protein component of saliva, especially in secreted by glands
salivariMUC5B mucins, MUC7
- .It is proposed a questionnaire and submitted it tothe laryngectomees patients, and healthy control.
Questions are eleven, relating to the report and the knowledge that the patient has with what the
main hypothesis of this work is indicated as the main "natural defence" — that is, the set of
"MUC5B mucins and MUC 7. Every question aimed to assess the impact of each risk factor,
provides answers to which are assigned a score from zero to three, meaning based on literature data
if is absent or implemented a partial and/or total impairment of the protective functions of salivary
mucins; maximum score compatible with sufficient integrity of mucous mucin system was
established within eight points. Analysis of the results has been evaluated statistically using the
Fischer Exact Test
The results indicate that ,66 %of laryngectomees before diagnosis would have exceeded the
established threshold limit value, while the data on the control was 15%.The results also show that
the presence of autoimmune disease is a risk factor for the onset of cancers of the oral cavity, (p =
0.0163), as well as the feedback from the men of xerostomia, (p = 0.0563).
These data indicate that the cancer of the larynx, are in strong correlation to smoking and sex, but
also the presence of autoimmune diseases, and between the anamnesis indicators must be
considered essential for a non-explainable xerostomia. The questionnaire proposed can be an
effective tool in predictive screening, and this study also proposes making at least to those that
exceed the value of eight an analysis of saliva to determine the salivary sialic acid/protein that
would make it possible to identify with certainty all the good people at risk for which establish a
protocol for monitoring and care
Page 3
INTRODUCTION AND BACKGROUND
At present, cancer research has made many advances in the study and in the fight against cancer,
especially in the field of molecular genetics, but from observation and analysis of epidemiological
data concerning the values for incidence of malignancies in all the districts of the human body you
can certainly say that in the field of prevention and early detection the way is still long. An example
of this comes from the analysis of the results obtained from the cancer genetics research relating to
the head-neck; According to a recent review (1) were highlighted been 601 regulatory genes tumour
tissue growth and 25 that control, significantly, the process of its activation. These data on the one
hand, confirm a significant difficulty in identifying with certainty the causes that bring cancer
education wing second indicate how for this district, so far, are not the only comprehensive
precautionary directions concerning the consumption of alcohol and tobacco, as a control for the
onset of various cancers. .In fact, for the oral cavity and larynx, there is a real program of
monitoring and screening, nor a self-evaluation mechanism as it does to any other sites, to which
this work proposes a different approach to the problem by directing efforts to the study and
knowledge of natural defences, by patients and medical specialists in Ent.This way you can reach
both the perception and the identification of a threshold of risk. The main natural defence for oral
cavity and larynx was identified based on clinical practice and review of the literature, in the protein
fraction of saliva and salivary mucins in mucins, secreted mainly by the sublingual glands and
mandible are glycosylated proteins or (2): in particular we refer in this connection to the hamlets
MUC5B, and MUC77).The glycosylation of salivary mucins, plays a fundamental role in protein
function as:
a) Is changed its chemical-physical structure
b) you have the protection of protein sites
c) creating loci of molecular recognition
d) the polysaccharide chain gives to the protein surface is very elastic.
It is believed that these mucins are absorbed into a protein layer at the interface of liquid saliva-air,
to form the so-called salivary film layer, which has an average thickness of 70-100 microns (3)
ensuring the fundamental rheological properties when the glycosylation process occurs regularly
(4), In this case is given to the typical appearance viscous saliva just lubricating substances. In this
way it Stratify, evenly, throughout the oral cavity allowing for effective protection of the mucosa
from different toxic agents, whether they be chemical, physical and biological, facilitates the first
phase of swallowing of food bolus, and due to its high lubricant, reduces friction between the vocal
cords, allowing regular phonation..A shortage of mucins, more or less strong and cronical , their
structural change, or their total privation from the entire oral cavity, exposing it to possible insults
chemical, physical and biological long-term can induce the formation of
4 page
the effects of cancer a total deprivation is largely verified (5), when you introduce in your mouth
food preparations like Bethel, a custom that has become entrenched in some Asian countries; this
food bolus contains large amounts of tannins (6) and in the concentrations lead to total precipitation
of salivary proteins consumer perception is expressed with a very strong sense of astringency
throughout the oral cavity and the consequences are of an absolute gravity so that in some countries
there is talk of health emergency for the very high incidence of cancers of the oral cavity (6) (7).We
speak in General of astringency when, the oral cavity is exposed to astringent (molecules, (3) and
more precisely it is referred to as the "complex of sensations caused by contraction, stretch, crimp
epithelium, as a result of exposure to substances such as alum and tannins In the seizure of mucin
from tannins, is because it is rich in PROLINE and this results in the formation of a very stable and
insoluble in water as a result of the formation of ties OH-groups, present in tannins, with oxygen
ketoimidic peptic bond (-CO-NH-) PROLINE, mucin inside (5) it is considered that these
Page 4
mucins are absorbed into a protein layer at the interface of liquid saliva-air, to form the so called
salivary film, ensuring the entire oral cavity and larynx lubrication protection This function is
ensured only under certain conditions rheology mucin-mucosa, which prevents the salivary film, in
the process of scrolling and renewal, abrasion phenomena laceration, (8) (9)) .In final mucins are
critical in maintaining the lubricity, adhering strongly to the surface in layers, formed with repulsive
areas, both in the sense that steric electrostatic. (10). (11). These introductory remarks are necessary
to understand, how likely mechanisms involving chronic albeit slight astringency, can be crucial in
establishing hazardous conditions around the mouth .For this reason during the discussion of this
work we focus on the possible causes that may lead to a structural change and / or a functional
deficit even slight, of these elements salivary protein, whose chronicity can however facilitate the
onset of tumors, in our case those of the larynx
.
Page 5
MATERIALS AND METHODS
As will be explained in the results and discussion section, was formulated an eleven questionnaire
multiple choice questions each of which is assigned a score from zero to three minimum value
indicating the absence of symptoms and/or illnesses and/or lack of habits, like smoking and alcohol.
The questionnaire was presented in the Milan section laryngectomees patients and in this first test
fifty were collected of which forty-six for men and four for women the average age of the male
population, as at the date of the intervention of laryngectomees is 61 years while that for women is
72.The same questionnaire was submitted to fifty volunteers visiting ENT, aged over 40 years: 30
women (average age 55 years) and 20 men (average age 66 years)
ANAMNESTICO-SURVEY QUESTIONNAIRE FOR LARYNGEAL CANCER
EPIDEMIOLOGICAL.
LAST NAME
SEX
M
FIRST NAME
F
AGE
AGE OF TOTAL LARYNGECTOMIE
SMOKE
NOT
YES
HABITS
HABITUALLY
EX SMOKING/
SCORE
2-3
1
TOTAL
ALCOHOL
NOT (0)
YES
CONSUMPTION
MEAL GLASS
MODERATE
HABITUALLY
TOTAL
SCORE
0
0-1
2
NORMAL SALIVATION
YES (0)
NOT
XEROSTOMIA
LOW
HIGH
TOTAL
SCORE
1
2
Page 6
HYPOGEUSIA (NORMAL)
SCORE
0
IPOGEUSIA (ALTERATED)
SCORE
1
FAMILIARITY CANCER
NOT(0)
YES
FAMILY
SISTER BROTHER
ONE PARENT
TWO PARENT
TOTAL
SCORE
1-2
1
2
FOOD INTOLLERANCE
SCORE
YES
1
FOOD INTOLLERANCE
SCORE
NOT
0
LIFESTYLE
PHYSICAL ACTIVITY
NOT (SEDENTARY) (3)
YES
INTENSITY
HIGH
LOW AND CONTINUE’
LOW
TOTAL
1
SCORE
0
0-1
2
Page 7
BALANCED AND VARIED DIET
( YES (0)
NOT
HABITS
SCORE
SWEET BREAD DOUGH MILK (PLENTY) 2-3
SWEET
BREAD
DOUGH MILK
(no 2
PLENTY)
TOTAL
BLOOD GROUPS
A
SCORE 1
B
SCORE 1
AUTOIMMUNE DISEASES
AB
SCORE
0
O
SCORE
0
NOT
YES (1)
DISEASES
DIABETES
THYROIDITIS
REUMATOID ARTHRITIS
CELIAC DISEASE
LUPUS
ULCERATIVE COLITIS
PERNICIOUS ANEMIA
SCLERODERMIA
OTHER
TOTAL
SCORE
STATISTICAL ANALYSIS: The questionnaire response data were analyzed using the Fisher
Exact Test that is the best test to verify a hypothesis that is used in the context of non-parametric
statistics, with two nominal variables and for small champion
Page 8
RESULTS
The study and elaboration of bibliographic data made it possible to fill out a questionnaire for which
responses have been assigned a variable risk score, and was found a maximum threshold value
(score ≥ 8). The questionnaire was then given to two populations: 50 patients for laryngectomees
patients the result, see table 1, indicates that the threshold limit value was exceeded by 66% of the
population interviewed the results also indicate, as on 50pazienti who have completed the
questionnaire, 33 of them (66 percent), including one woman, at the time of diagnosis have
exceeded this value. Table 2 shows the results for the people, of the same population, they have
reached the 8 specifying individual parameters and how to, Percentagewise, have been overcome
risk thresholds given and accepted in the questionnaire, with particular emphasis on the age of onset
(61 percent), smoke (87%) diet (69%), and Xerostomia (57%) Autoimmune Diseases (53 per cent),
blood (64).The 22% of them also recognises, at the time of diagnosis the presence of all these
factors. In absolute terms, it can be seen from table 1 that the data confirm the role on the incidence
of laryngeal Ca, smoking, gender, as well as of the contribution resulting from the presence of
autoimmune diseases, mainly diabetes, (20% of people), and nonspecific symptom, relative to the
dry mouth (32.It should be noted that the percentage of patients with oral cancer that has an
autoimmune disease is significantly higher than for the general population in Italy (34% vs 1%, p
0.0001 test < proportions). Also, in the same patients, smoking and the presence of an autoimmune
disease are two associated risk factors (p = 0.1211 with Fisher exact test). Population data are given
in tables 3 and 4, and as you can see at the moment of the presentation and the formulation of the
questionnaire only 7 patients have surpassed the score of eight points without manifesting any
symptoms indicative of a laryngeal pathology can be present, as confirmed by physical
examination. Of these seven patients, six are men, all heavy smokers, drinkers, not usual careful
diets or lifestyles details, and all with aged over 65 years, to which the achievement of the eightpoint score is attributable mainly to assigned parameters. In any case, this population subgroup
((seven persons) both have autoimmune diseases that a smoker and all these patients was strongly
recommended a radical lifestyle change and a checkups after six months. From the results, we see
that the presence of an autoimmune disease is a significant risk factor for cancer of the oral cavity
(34% vs. 12% in the laryngectomees patients in controls, p = 0.0163 with Fisher exact test). In
addition, the data suggest that could be individual risk factors hypogeusia and also xerostomia (p =
0.0563 and p = 0.0559, respectively) and that the latter might be a specific risk factor for men
(32.6% in men vs. 5% in the laryngectomees patients men of control, p = 0.0260 with Fisher exact
test). Globally, with a threshold value of 8, the survey has obtained a sensitivity of 66% and a
specificity of 86% for predicting the risk of cancer of the oral cavity (0.0001 p < with logistic
regression).
Page 9
DISCUSSION
The score by eight points, beyond which is established the beginning of risk threshold corresponds
to 2/3 of the questions in the questionnaire, with a positive response (1 value) for each question, and
half of this score can be reached with only three patients individual factors that, statistically, occur
in most cases of the larynx cancers age, smoking and sex. Literature data, it is clear that in the
development of laryngeal, Ca a preponderant role is attributed to age, smoking and another to sex:
for this evidence was assigned a risk 1 value for the male only and a score of 3 (as maximum) for
heavy smokers. It is also clear; these three parameters alone cannot be the cause of a possible
outbreak of the larynx tumours, which are, of course, as well as other factors, as has been
sufficiently explained in the discussion of this work. Their single contribution anyway, except in
rare cases, like familiarity for tumours, multiple autoimmune diseases, nutrition and the type B
blood group and/or does not exceed the value of 1 (maximum 2) to evaluate and examine in detail
the results of the questionnaire answers. it must be said that the idea of preventive approach
regarding the defences of the oral cavity and larynx in particular ,was determined not only by
increasing indications of literature but also from clinical and anamnestic feedback on patients
laryngectomees patients, functional changes to the mucous mucin. Many of them in the checkups,
stimulated to remember details symptoms before diagnosis remembered well the feeling of dryness
in the mouth, a phenomenon that mostly was intermittent and not exacerbated by particular eating
habits...This anamnestico, allowed to present the hypothesis of xerostomia tied to functional
changes of salivary mucins and/or a shortage, such as to modify the lubricity of the spittle. The
study of literature data show that this can happen when at the stage of glycosylation, the ratio is
varied in substituent’s O-linked carbohydrates with protein amino acids, and in particular the
concentration of sialic acid. Literature data agree in attributing to sialic acid a given concentration
range in glycosylated mucin, in comparison with the other sugars, (4), between the 5 and the 9%
mole/mole which ensures the appropriate quality lubricants mucins, and/or protective, fundamental
to the defence of oral biotope. However this doesn't happen for a flaw in the concentration of
protein-bound sialic acid, regardless of the conditions that created it. ..These conditions can be
realized for various reasons, the main of which are generally due to an increase of the activity of the
enzyme sialinidasi, mechanism not yet explained, and probably multifactorial, as we shall see, or,
for an increase of oxidative stress. In the first case in the saliva will be an increase in the
concentration of sialic acid free while in the second we will have an increase in the amount of
malondialdehyde, generated over that compound from lipid per oxidation of membrane, also from
the same degradation related to sialic acid mucins (12). In both cases the saliva increases its
viscosity (9)), it inhibits the same lubricating capacity, and the spatial structure changed, prepares,
the oral cavity to various diseases. Ultimately mucins are crucial in maintaining the protective
power and lubricant, if their glycosylation defines a spatially correct structure. In this case it may be
properly solvated by water molecules and form a mobile film but able to adhere strongly to the
surface of the mucous membrane with subsequent layers, with repulsive areas, both electrostatic
and steric.(13).(14). Recent work has shown a strong correlation between glycosylation, bad acid
concentration
Salivary sialic and laryngeal Ca (15) (16) (17), confirming the correct investigative approach in
formulating the questionnaire and propose a subsequent investigation that finds the sialic acid in
saliva. In fact, high levels of sialic acid in saliva and blood were detected in patients with laryngeal
cancer and precancerous conditions of the oral cavity (18). This figure, in some cases, it is
suggested to increase proteins and sugars in serum and in saliva (19)) in patients with squamous cell
carcinoma. The question of the questionnaire concerning the presence of autoimmune diseases also
take account of these findings in literature: in autoimmune diseases in addition to present itself very
often a dry mouth, you have high serum concentrations of sialic acid (20) (21). Other topics
Page 10
covered, on the consumption and/or abuse of alcohol and tobacco, are also suspects in the logic of
negative interactions with the natural defences of the mouth and larynx, particularly mucin. Also in
This case the most recent literature data (22) (23) (24), predispose to store the initial hypothesis of
this work. The questionnaire has been submitted the application for possible involvement of genetic
nature. In Medical Genetics, cancers of the oral cavity and larynx are not at present included in that
5-10% of "hereditary neoplasia".These are cases in which a single gene alterations able to confer a
high risk of cancer even at a young age, usually less than 40 – 45 years. In any case, the geneticist
has to rebuild a family tree with the neoplastic diseases for all family members, possibly in addition
to first degree relatives, also those of the second degree (maternal and paternal uncles, cousins,
grandparents).In our case it was consciously simplified the question, by adapting the concept of
"familiar" in situations where multiple tumours were found in younger than 45-50 years of tumours
and, in the family of the patient, including in it the paternal and maternal grandparents. In the
questionnaire then there is a question concerning the identification of patients, of possible food
intolerances, that argument is particularly delicate because of its complexity, but worthy of study.
The first factor to consider is the biochemical evidence that correlates type autoimmune diseases
statistically with immune reactions triggered by allergens present in certain foods (especially dairy
products and cereals such as lactose and gliadin.The second factor, no less important, concerns the
effects arising from the elimination by the diet of those foods where the person is intolerant. With a
power source, budget to avoid allergic reactions are less in the daily diet, many of those compounds
needed for the normal life cycle of the intestinal flora that are important in the immune system.(25).
This stems from the fact that the cycle immune defence depends essentially by metabolites that
bacteria produce compounds alimentary that once formed the bind "sensing proteins", e.g., GPR43,
which in turn being coupled to specific receptors modulate the immune response).The lack of
certain metabolites that could come from the breakdown of certain foods responsible for allergies
very often those rich in fibres, can stop this cycle, reducing the immune system: According to
epidemiological data, the increase in diabetes in Western countries is attributable to these factors. It
is clear, therefore, how in the face of this eventuality, you can bind even the concept of a balanced
diet, not excessive in some parts, components, and backed by a good physical activity. Regarding
the question about blood groups, there is to say at the outset that recent epidemiological studies
showed that the incidence of tumours in various districts head neck and blood group function (26).
We also noted that the glycosylation of mucins, saliva, and in particular, the relationship between
sialic acid and other sugars, reflect the distinct gene expression on blood groups (27), assigning a
score equal to 1, and for Group B, the most significant risk for cancer of the larynx is to group A,
oral cavity and salivary glands, of only three individual factors that, statistically, occur in
most cases of cancer in the larynx, i.e. age, sex and smoking. Literature data, it is clear that in the
development of laryngeal, Ca a preponderant role is attributed to age, smoking and another to sex:
for this evidence was assigned a risk 1 value for the male only and a score of 3 (as maximum) for
heavy smokers. It is also clear that these three parameters alone cannot be the cause of a possible
outbreak of the larynx cancers, which are, of course, as well as other factors, whose single
contribution anyway, except in rare cases, like familiarity for tumours, multiple autoimmune
diseases, nutrition and the type B blood group and/or, does not exceed the value of 1 (maximum 2)
recent literature data concerning epidemiological research (28) (29), indicative of possible
correlation with cancers of the larynx and mouth. From the observation of the results points out
finally as there is a different tumour incidence as a function of sex, whose role in the development
of cancers of the mouth, larynx and more generally of the district head neck (HNC), is still under
discussion. The last and most significant data, analyzed in a recent review, (30) show that in a large
series of patients with HNC, estrogens levels in females play a protective role in the development of
cancer, unlike the males that have a lower level of them so they are predisposed. .This hypothesis
Page 11
appears to be supported by experimental evidence that the destruction of the liver function in
alcoholic’s leads to a substantial alteration in the metabolism of sex hormones, estrogens and
testosterone, and this would explain why the many alcoholics are high-risk individuals in the
development of cancers of the oral cavity and larynx. The results obtained confirm the possibility of
easy and useful application of the questionnaire. In outpatient scope, such as screening for all
patients visiting ENT, to identify people at risk. The authors also consider plausible all assumptions
made at the onset of laryngeal Ca, including even the newer one, which calls into question the HPV
(31), hypothesis that ultimately does not conflict at all with the role of mucins in the prevention of
cancer of the larynx. With this work, however, is thought to have identified a possible new and
innovative approach to the problem. The questionnaire, in fact designed, to the knowledge of
natural defences it is then structured, until the final definition, with the survey history on patients
already undergoing of laryngectomees, coypu are thus obtained the results to "rear", which would
have indicated how il66 cables% of them if he had prepared the questionnaire, would have been at
serious risk, while another 25% borderline Probably though on the latter population sample, he
could maintain a salivary analysis prior to the determination of sialic acid, or rather (21), total
protein ratio/sialic acid, you would have found a 91% of people at high risk. In figures 1 and 2, we
finally tried to outline the numerous physical and chemical processes-biological that might
somehow interact in both stages of salivary mucins or after altering substantially more or less their
inherent properties.
Page 12
CONCLUSIONS
This work, while not contradicting any of the cases related to cancer, especially those genetic,
emphasizes the need to structure more productively the preventive approach to all patients visiting
ENT. enhancing the current knowledge of the natural defenses and making participants and
protagonists physician and patient in the outpatient setting, the questionnaire, may well become a
valuable aid for one first screening for all patients, regardless of ENT pathology for which is
required to visit .In this way on a large segment of the population can be identified, all the people
who exceeded the score of eight points, must be evaluated for a possible risk factor for diseases of
the oral cavity and in particular of larynx..Per these patients the physician should immediately
establish a prevention protocol designed to eliminate and / or reduce risk factors: smoking
cessation, varied and balanced diet, good lifestyle, metabolic control relative to any autoimmune
diseases, and dosage of salivary protein ratio total / sialic acid are the first factors intervention .The
physician can then determine on the basis of the results after the completion of the second
questionnaire, the chronology of the subsequent follow-up.
Page 13
TABLE 1 RESULTS - TOTAL LARINGECTOMEES
RISK FACTORS
M
≥65
YEARS
%
F
%
≥60
YEARS
TOTAL
AGE
30
SMOKE
%
65.2
1
25
31
62
33
71.3
1
25
34
68
ALCOHOL
3
6.5
0
0
3
6
CANCER
FAMIL
2
4
1
50
3
6
XEROSTOMIA.
15
32.6
1
25
16
32
HYPOGEUSIA
4
8.7
1
25
5
10
PHYSICAL
ACTIVITY
DIET
10
21.7
3
75
13
26
15
32.6
2
50
17
34
FOOD
INTOLLERANCE
BLOOD
GROUPS
AUTOIMMUNE
DISEASES
4
8.7
1
25
5
10
14
30.4
3
75
17
34
16
34.8
1
25
17
34
PAGE 14
TABLE 2 (DATA PROCESSING QUESTIONNAIRE)
FINAL ELABORATION (for 33 patient over 8 score)
RISK FACTORS
% IMPACT
AGE 'ONSET
CANCER
SMOKE RS
61
ALCOHOL
9
FAMILY 'CANCER
3
XEROSTOMIA
57
HYPOGEUSIA
22
FOOD
INTOLLERANCE
PHYSIC ACTIVITY
15
DIET
69
BLOOD GROUPS
53
AUTOIMMUNE
DISEASES
64
87
35
PAGE 15
TABLE 3 - CONTROL POPULATION
30 WOMENS
20 MENS
RISK FACTORS
M≥65
YEARS
%
F≥60
YEARS
%
TOTAL
AGE
13
65
10
33
23
60
SMOKE
15
75
10
33
25
50
0.1033
ALCOHOL
5
25
1
3
6
12
0.4870
CANCER FAM
1
5
2
23
3
20
0.7150
XEROSTOMIA.
1
5
6
20
7
14
0.0559
HYPOGEUSIA .
0
0
0
0
0
0
0.0563
PHYSICAL
ACTIVITY
DIET
7
35
12
36
19
38
0.2837
7
35
9
27
16
32
1.0000
5
2
7
3
6
0.7150
10
7
23
9
18
0.1095
5
5
17
6
13
0.0163
FOOD
1
INTOLLERANCE
BLOOD
2
GROUPS
AUTOIMMUNE 1
DISEASES
%
FISHER
EXACT TEST
COMPLIANCE
CHECKS
PAGE 16
TABLE 4 CONTROL GROUP NUMBER 7 PEOPLE
SCORE POINTS OVER 8
RISK FACTORS
NUM
%
AGE
6
86
SMOKERS
6
86
ALCOHOL
4
57
FAMILY CANCER
1
14
XEROSTOMIA
1
14
HYPOGEUSIA
0
0
FOOD
INTOLERANCE
PHYSIC ACTIVITY
1
14
4
57
DIET
5
71
BLOOD GROUPS
1
14
AUTOIMMUNE
DUSEASES
2
29
Page 17
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