Balaji

et al:Amit et al/; V

ISSN No: 2582-0559

ABSTRACT

INTRODUCTION:

Malignant neoplasm is a major cause of death in

developed countries, and its incidence continues to grow. Diabetes mellitus is
a  serious  and  leading  health  problem.  Recent  studies  demonstrated  that
Diabetes  mellitus (DM) was associated with a higher risk of Head and Neck
cancer. Only a few population-based studies, especially in Asian populations,
have  addressed  these  issues.  Thus,  this  study  aimed  at  assessing  the
relationship between Diabetes mellitus and Head and Neck Cancer (HNC) in
reference to their socio-economic status.

MATERIALS AND METHODS:

The present study was conducted on 483

HNC  patients  aged  above  15  years.  The  data  was  collected  from  patients
reporting  to  Mahavir  Cancer  Institute  &  Research  Centre,  Patna,  and  Rama
Dental College Hospital and Research Center, Kanpur. Blood sugar level was
tested to assess the status of diabetes mellitus. The demographic details such
as  place,  social-economic  status  (SES),  age  and  sex  were  recorded.  Control
group of 100 people aged above  15 years  were selected with habits of using
tobacco  products  and  without  any  oral  precancerous  lesion/conditions.  Odds
ratios  (OR)  and  95%  confidence  intervals  (CI)  were  estimated  using
unconditional logistic regression.

RESULTS:

Of 483 patients, 70 patients (14.4%) had DM showing no overall

relationship with HNC.  A major number of HNC with DM was  more in high
socioeconomic  status  patients  41.7%  (p<0.05),  showing  strong  association
whereas  for low SES it was 3.4% (p>0.05). Out of overall Diabetes  mellitus
(DM), there were 77.1% of male and 22.8% were female.

CONCLUSION:

Diabetes was weakly associated with HNC, but we

observed evidence of a relationship with the socioeconomic group. People
with HNC and low socioeconomic status showed less association with
diabetes than people with high socioeconomic status.

KEY WORDS:

Socioeconomic status, Diabetes mellitus, Head and Neck

Cancer

EVALUATION OF ASSOCIATION OF DIABETES MELLITUS WITH
HEAD AND NECK CANCER: A CROSS-SECTIONAL STUDY

Dr. Amit Kumar, Dr. Gayathri Ramesh*, Dr. Vishal Chandra, Dr. Gaurav Rai**, Dr. Antima Saxena***, Dr. Abhishek

Anand****

Department of Oral and Maxillofacial Pathology, Rama Dental College Hospital and Research Center, Kanpur, India,

*Department of Dentistry, Chamarajanagar Institute of Medical Sciences, Yadapura Kasaba, Hobli, Chamrajnagar, India,

**Department of Oral and Maxillofacial Surgery, Buddha Institute of Dental Science and Hospitals, Kankarbagh; Patna, India,

***Department of Public Health Dentistry, Institute of Dental Sciences, Siksha ‘O’ Anusandhan(Deemed to be University),

Kalinganagar, Bhubaneswar, Odisha, India****Department of dentistry, Narayan medical College and Hospital, Sasaram, India

Address for correspondence

Dr. Gayathri Ramesh, MDS.,

Associate Professor, Department of Dentistry,

Chamarajanagar Institute of Medical Sciences,

Yadapura Kasaba, Hobli, Chamrajnagar 571313, India

Email id

-amug3r@gmail.com

Received: 30.10.2020

First Published: 25.01.2021

Accepted: 08.01.2021

Published: 27.03.2021

ORIGINAL STUDY

DOI:1.37841/jidam_2021_V8_I1_02

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ISSN No: 2582-0559

INTRODUCTION

Cancer  is  a  name  given  to  group  of  diseases  characterized
by  the  growth  of  abnormal  cells  beyond  their  usual
boundaries that can then invade adjoining parts of the body
and/or  spread  to  other  organs.  Other  common  terms  used
are malignant tumors and neoplasms. Cancer affects almost
any part of the body and has many anatomic and molecular
subtypes which force specific management strategies.
Cancer is second main cause of death globally and accounts
for  8.8  million  deaths  in  2015.  Lung,  prostate,  colorectal,
stomach  and  liver  cancer  are  the  most  common  types  of
cancer  in  men,  while  breast,  colorectal,  lung,  cervix  and
stomach cancer are the most common among women.

An increasing figure of evidence advocates that certain
types of cancer are more common in people with diabetes
mellitus (DM).

2,3

Previous studies

4-7

report elevated risks of

cancers  of  the  liver,  biliary  tract,  pancreas,  stomach,
colorectum, kidney, bladder, breast, and endometrium but a
decreased  risk  of  prostate  cancer.  Numerous  mechanisms
have  been  projected  as  part  of  the  possible  carcinogenic
process in DM. For example, untreated hyperglycemia may
contribute  to  tumor  growth  because  of  the  increased  need
for  glucose  to  fuel  proliferation  in  neoplasms.

In patients

with DM, a single hyperglycemia-induced process in which
the mitochondrial electron transport chain overproduces
superoxide

and

reactive

oxygen

species

generated.

1,8

Exposure to high levels of insulin and insulin-

like growth factors (IGFs) in DM increases cellular
proliferation and activation of the oncogenic epidermal
growth factor receptor.

Additionally, IGF and its receptors

have mitogenic and antiapoptotic effects and can be source
of malignant transformation.

10,11

Few studies with DM have also been related with HNC,
these results are still debatable. In few studies,

patients had an increased risk of HNC cancer, while in other
studies this risk was decreased. Some studies with DM have
also been associated with HNC, these results are still
controversial.

One of the possible explanations could be

given for the inverse association between DM and HNC is
the difference in their socioeconomic status.
This is the first study of its kind to study the association of
diabetes and SES with HNC patients with effects of habits.

AIM AND OBJECTIVES

This study aims to evaluate the association between DM,
HNC and SES of HNC patients.

MATERIALS AND METHODS

The present study was conducted on 500 Head & Neck
cancer patients reporting at 2 different centers- - Mahavir
Cancer Institute & Research Centre, Patna, and at Rama

Dental  College  Hospital  and  Research  Center,  Kanpur.
Out of which 17 cases was rejected due to insufficient data.
The number of cases included were only 483 in this study.
The  control  group  included  age  and  gender-matched
100patients  with  habits  without  any  potentially  malignant
diseases  (PMD).  Informed  consent  was  obtained  from  the
patient.  Ethical  clearance  was  taken  from  Rama  Dental
College,  Hospital  and  Research  Centre,  Kanpur  and
Mahavir  Cancer  Institute  &  Research  Centre,  Patna.
Inclusion  criteria  included  patients  of  age  group  above  15
years of both genders with tobacco habits and diagnosed for
oral  cancer.  Patients  below  15  years  of  age,  patients  with
any  other  systemic  conditions  and  on  any  medication
affecting  blood  glucose  levels  and  patients  having  any
PMD’s were excluded.
Participants  were  interviewed  using  a  standardized
questionnaire to collect information about age, sex, DM and
social  economic  status  (SES),  tobacco  consumption,  and
alcohol  consumption  Blood  samples  were  collected  from
cases and controls and fasting blood glucose levels and 2hr
postprandial  levels  were  estimated.  Glucose  oxidase  -
peroxidase  GOD/POD  method  was  used  for  the  estimation
of  glucose  levels.  It  was  based  on  Trinder’s  method.
According  to  the  American  Diabetes  Association  (ADA)
2018  Guidelines  it  was  considered  positive  for  diabetes
when values were FPG ≥126 mg/dL (7.0mmol/L)* (Fasting
is  defined  as  no  caloric  intake  for  ≥8  hours)  PG  ≥200
mg/dL (11.1mmol/L) during OGTT (75g)* Using a glucose
load  containing  the  equivalent  of  75g  anhydrous  glucose
dissolved in water.

STATISTICAL ANALYSIS

All the findings were entered in Microsoft Excel using
SPSS 20.0 software and Odds ratios (OR) and 95% CI were
estimated using unconditional logistic regression. The
degree of freedom between variables were also observed. P-
value < 0.05 represents statistically significant and P-value
> 0.05 represents statistically non-significant.

RESULTS

TABLE  1:  Shows  a  total  of  483  cases  and  100  controls.
Among  these,  cases  with  tobacco  use  and  alcohol
consumption  were  more  likely  to  be  males  with  78.2%,
while  females comprised of 22.1%. About 50% of patients
were  of  age  between  50  to  64  years  of  age.  Most  (71.4%)
cases  were  of  squamous  cell  carcinomas.  Approximately
30%  of  cases  were  diagnosed  with  cancers  of  the  oro-
pharynx  and  hypopharynx  or  larynx,  and  70%  of  the  cases
were diagnosed with other cancers of the oral cavity
Table 2: It was found that diabetes  mellitus (DM) was not
associated  with  HNC  in  models  adjusted  for  age,  sex,

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tobacco  use,  and  alcohol  (OR,  0.95;  95%  CI,  0.83–
1.08; Table 2). Results for minimally adjusted models were
similar  to  results  obtained  with  adjustment  for  age,  race,
sex, tobacco use and alcohol. ORs  were slightly  higher  for
women than for men, but a comparison of models with and
without  a  product  term  for  sex  and  diabetes  yielded
p=0.091.  Overall  Diabetes  mellitus  (DM)  cases  there  were
77.1% male and 22.8% were female.
Table 3: In these table HNC cases were divided in respect
to  their  SES  cases.  Low  SES  were  71.2%  of  total  cases  in
which diabetes mellitus (DM) cases were only 3.4% with p-
value being 0.771.  This showed no relationship with HNC
while  cases  which  were  high  of  SES  were  28.7%,  butonly

DM cases in them were 41.7%. among the controls it was
17.1% with p-value of 0.021 that showed direct relationship
with HNC.

DISCUSSION

483 HNC patients involved in the examination bunch were
all priorly histopathological analyzed cases. Age sex and
social economic status coordinated controls with harmful
propensities and with no premalignant lesion were enrolled.

HNC was significantly higher among patients aged between
50 to 64 years comprising around 50%.

Although a

positive link between DM and many types of cancers

Table 1: Showing characteristics of the 483 cases and the 100 controls.

AGE

Cases

Controls

n (483)

n (100)

12–39

3.7

40–45

5.6

45–49

10.5

50–54

15.1

55–59

18.6

60–64

17.5

65–69

14.2

70–74

9.3

75–94

5.1

Sex

Women

107

22.1

Men

378

78.2

Tobacco use status

Never

1.8

User

474

98.1

100

Alcohol drinking status

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Never

19.2

User

390

80.7

Sub-site of tumour

Oral cavity

368

69.3

Oro- and

hypopharynx or

larynx

148

30.6

Histology of tumour

Squamous cell

388

80.3

Other

19.6

Previous systemic diseases

Yes

103

21.3

380

78.6

Table 2: Shows adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between head and neck

cancer and DM

Case 483 n(%)

Control 100 n(%)

95%CI

p-value*

All

70(14.4)

8(8)

0.95

0.83–1.08

0.091

Women

16(22.8)

1(12.5)

1.06

0.82–1.38

0.078

Men

54(77.1)

7(87.5)

0.91

0.79–1.06

0.052

Table 3: Shows adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between head and neck

cancer and DM in reference with SOCIAL ECONOMIC STATUS (SES)

SOCIAL ECONOMIC

STATUS (SES) n (%)

Case 483 n (%)

Control 100n

(%)

95%CI

p-value*

Low SES

344(71.2)

65(65)

1.498

0.84-2.10

0.025

Diabetes

12(3.4)

2(3.07)

1.24

0.27-5.66

0.771

Men

8(66.6)

2(100)

3.58

1.17-6.94

0.001

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Women

4(33.3)

1.88

0.10-35.3

0.673

High SES

139(28.7)

35(35)

0.75

0.361-1.57

0.457

Diabetes

58(41.7)

6(17.1)

1.55

1.070-2.24

0.021

Men

46(79.3)

5(83.3)

3.358

1.726-7.16

0.003

Women

12(20.6)

1(16.6)

2.25

0.32-19.2

0.372

DM  exceptionally  type  2  is  considerably  more  identified
with way of life. It was found that DM prevalence was high
in High SES individuals  in comparison to Low SES  this is
because  DM  is  a  life  style  disease  which  is  influenced  by
age  kind  of  food  habbit  BMI  weight,  central  obesity  and
physical exercise is significant hazard factor for it

. So, in

this  current  investigation  as  a  result  of  these  realities  we
isolate  our  cases  into  social  economic  status.  At  the  point
when  we  isolated  this  information  into  social  economic
status we found that 71.2 individuals were of Low SES and
28.7%  were  High  SES  a  The  explanation  could  be  that
HNC  in  India  is  primarily  because  of  smokeless  tobacco
like khaini zarda, etc and areca nut like panmasal (This item
without  tobacco  is  known  as  'panmasala'  while  the  item
with  tobacco  is  known  as  'gutkha)'

smoke tobacco like

bidi  (Indian  explicit  non-filtered  cigarette)  which  are
broadly  devoured  by  individuals  who  are  in  Low  SES  like
work class, vegetable vendor, cart puller and so forth due to
their  work  pressure  and  because  of  bidi  being  less
expensive  then  cigarettes.  Whereas  smoke  tobacco  like
cigarette  are  favored  by  high  SES  individuals.  In  India,
where oral cancer growth is a striking frequency, just short
of what one-fifth (19%) of tobacco consumed is in form of
cigarettes.

Around  26%  of  all  adults  in  India  use  Smokeless  tobacco
by  chewing,  applying  it  to  the  teeth  and  gums,  or  by
sniffing.  Consumption  of  smokeless  tobacco  (SLT)  (26%)
is  more  prevalent  than  various  smoking  tobacco.  Of  the
26%  of  all  adults  who  use  SLT,  21%  use  SLT  every  day
and the other 5% use it occasionally. A little additional than
2%  of  the  adults  who  were  SLT  users  in  the  past,  either
daily  or  occasionally,  have  since  stopped  such  use
completely.  Use  of  SLT  amid  males  (33%)  is  higher  than
females (18%); in contrast, smoking has a sharp difference
between the two genders. In rural areas, 29% of adults use
SLT,  whereas  the  figure  is  18%  in  urban  areas  is  as  per
WHO in India 27
There are very few studies done similar to the present study
and hence comparison in detail is limited.
Survey  by  Corsi  and  Subramanian  in  2014  evaluated
socioeconomic  differences  in  smoking  behavior  among

males in India and reported that people who were wealthier,
more educated, and having a decent job were more prone to
cigarette  smoking,  and  on  the  other  side,  people  who  are
less educated with poor socioeconomic status had a habit of
bidi  smoking.  This  rare  difference  in  socioeconomic
inclines  in  consumption  of  two  smoking  habits  reported
among  the  males  raises  serious  concern  and  curiosity  to
tackle this problem. Also, a greater concern that is ignored
in  many  studies  is  growing  prevalence  of  dual  tobacco
consumption  amid  the  population  and  forming  a  tobacco
quit strategy.

Studies  confirm  that  people  consuming  smokeless  tobacco
and  bidi  are  at  more  risk  of  developing  HNC  then  people
consuming  filtered  cigarettes  in  India

26,29,30

This clearly

shows HNCare much more prone to people of low SES then
High SES.
By  the  above  conversation  2  focuses  are  clear,  one  DM  is
identified with High SES on account of their way of life and
second  is  HNC  is  increasingly  inclined  in  LOW  SES
individuals  since  utilization  of  smokeless  tobacco  and  bidi
smoking.
So  in  this  current  investigation,  it  was  discovered  that  in
71.2%  of  instances  of  HNC  were  of  Low  SES  and  just  12
instances  of  DM  were  discovered  that  is just 3.4% p-value
0.77  demonstrating  no  applicable  connection  among  HNC
and  DM.  Very  little  investigation  has  been  done  till  date
including this subject so there isn't a lot of study accessible
to talk about with results obtained t in this examination.
While in High SES instances of HNC were 28.7% in which
41.7%  cases  were  of  DM  which  show  affiliation  DM  with
HNC p-value 0.021
By  this  above  conversation  we  can  say  that  DM  is  way  of
life  ailment  so  its  less  pervasive  in  Low  SES  individuals
and HNC is progressively regular in Low SES. So when we
look generally HNC isn't related with DM yet when we find
in  individuals  With  High  SES  where  DM  is  basic  in  them
HNC is related with DM.
This  can  be  comprehended  by  pathogenesis  of  Diabetes
mellitus  and  malignant  growth.  They  are  multifactorial
maladies;  a  few  potential  pathophysiological  pathways  can
add  to  their  reliance.  Nonetheless,  most  components
fundamental  the  relationship  among  DM  and  the  ensuing

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ISSN No: 2582-0559

advancement  of  HNC  stay  hazy.  A  likely  reason  for  the
expanded danger of HNC in patients with recently analyzed
DM  may  be  shared  hereditary  hazard  factors,  DM-related
metabolic  morbidities  (eg,  hypertension  and  dyslipidemia),
stoutness,  maturing,  and  sex  as  the  connection  among  DM
and other cancers.

32,33

Epigenetic adjustments of the acquired or obtained
hereditary changes in disease may give another conceivable
component connecting the reasons for disease and DM.

For  instance,  RRAD  (OMIM  179503),  an  individual  from
the  Ras-related  GTPase  superfamily,  is  every  now  and
again  methylated  in  various  human  dangerous  tumors.

human malignancies, RRAD may assume inverse jobs as an
oncogene or a tumor silencer, contingent upon the
malignancy and cell type.

RRAD has been suggested to be a

tumor suppressor gene in several human malignant tumors,
including malignant mesothelioma, lung cancer, breast
cancer,

cervical

cancer,

prostate

cancer,

and

NPC

RRAD is

epigenetically

inactivated

NPC.

Epigenetic down-regulation of RRAD might disrupt the
pathways downstream of the tumor suppressor p53 and lead
to a malignant and aggressive phenotype.

Conversely,

RRAD  translocates  Grap2  and  GCIP  from  the  core  to  the
cytoplasm,  in  this  manner  hindering  the  tumor  silencer
movement  of  GCIP,  which  happens  in  the  nucleus.

Consequently,

RRAD may promote carcinogenesis at least

in part by inhibiting GCIP-mediated tumor suppression

One possible mechanism that links DM to the development
of HNC is long-term exposure to hyperinsulinemia, which
leads to breast cancer. Insulin is a potent growth factor that
promotes proliferation and carcinogenesis in various ways,
directly

and

through

IGF.

Another

reasonable

explanation is hyperglycemia, which may directly promote
tumors:

cancer

cells

rely

increased

glucose

consumption.

The

literature

also

reports

that

hyperglycemia induces DNA damage, down-regulate the
expression of antioxidants, and increases the generation of
reactive oxygen species.

This is the primary investigation corresponding the
relationship of DM and HNC concerning their social
monetary status and first of its sort

CONCLUSION:

we reason that DM isn't related to HNC by and large yet as
we  realize  that  some  place  frequency  of  DM  relies  upon
way  of  life  of  an  individual  and  HNC  is  progressively
inclined in Low SES individuals and these individuals have
low occurrence of  DM and in high SES individuals DM is
related  with HNC. This  is just on the grounds  that number
instances  of  DM  is  more  in  High  SES  individuals.  Further

broad investigation is required with enormous example size
to get increasingly productive connection.

FINANCIAL SUPPORT AND SPONSORSHIP:

Nil

CONFLICTS OF INTEREST:

There are no conflicts of interest.

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