Introduction
Thyroid cancer (TC) is one of the most common cancers
worldwide. The incidence of TC has grown significantly
in recent decades. This dramatically rising might
be due to early diagnosis by neck ultrasound; of course, it cannot be justifiable for large size tumors. However,
it can be attributed to increasing screening and also potential
or unknown risk factors.[]
Type 2 diabetes (DM) is a major health problem in
Iran, as well as in other countries. The prevalence of
DM is 11.4% in the Iranian adult population.[] DM, as a potential risk factor, was proposed for some cancers.
The significant associations between DM and
colon, breast, endometrium, liver, pancreas and bladder
cancer have been seen.[] The ionizing radiation is
the only of known risk factor for TC. From the possible
risk factors of TC can be mentioned to inadequate
or overdose of iodine.[] The role of DM on TC is remained
to be elucidated. In the literature review, the
studies with pooled analysis were found a significant
relationship between TC and DM, but there was no association
in the male patients and Asian population.
[,] Since the incidence of DM and TC can be depended
on the climate condition, ethnicity and lifestyle
in the various regions of the world [,], our study is
a sample of TC and DM in Iran. We have investigated
ABO blood group as a potential agent for TC due to
the recent reports from the role of blood groups in the
development of cancers.[-]
Methods
This retrospective comparative study was conducted in
2010-2017 Loghman Hakim Hospital. This study was
approved by the medical ethics committee of Shahid
Beheshti University of medical sciences.
The case group was the patients with thyroid cancer.
The medical records of them were extracted from
hospital information system from March 21, 2010 to,
2017 based on ICD-10 code (C73). The inclusion criteria
for this group included of laboratory data for ABO
blood group, diabetes screening and pathological diagnosis
of TC. The exclusion criteria were type 1 diabetes,
the absence of blood types and fasting plasma
glucose or random plasma glucose. The database was
104 patients with TC that two patients had no primary
TC, 5entries were duplicates and 10 patients had no information
about studied variables. Of the original data,
87 patients remained for analysis (83.6%). The control
group was the individuals" cancer-free that were visited
in an outpatients clinic. They were 1045 individuals
without cancer history that 929 individuals were selected
using the same period and inclusion criteria of
the case group. Overall, the selection of the individuals
was non-probability sampling and their information
was confidentially kept by our colleagues in this study.
Statistical Analysis
We entered data into SPSS version 18 and compared
two groups concerning the demographic variables and
the proportion of diabetes and ABO blood group. We
compared the proportion of diabetes in studied groups, two age groups (less than 60 years and 60years or older)
and sex using the χ2 test. Univariate and Multivariate
unconditional logistic regression were applied to determine
the odds ratio of thyroid cancer based on diabetes
and ABO blood group. Subgroup analysis was also performed
for papillary thyroid cancer (PTC) and non-papillary
thyroid cancer (non-PTC). In our analysis, parametric
tests were used, if the assumptions of those were
set, otherwise the nonparametric tests were applied. The
significant level was considered less than 0.05.
Results
The Baseline Characteristics
The demographic analysis of the case group and control
group is presented in Table 1. The mean age of
studied groups was no significant difference (p=0.209);
59.8% and 31.3% were female in case group and control
group, respectively (p<0.001).The proportion of
diabetes was significantly higher in the case group than
the control group (13.8% vs. 3.9%; p<0.001). Of 87 patients
with TC, 68 patients (78.2%) had papillary thyroid
carcinoma (PTC), and 8(9.2%), 7 (8.0%), 4 (4.6%)
had follicular thyroid carcinoma (FTC), anaplastic
thyroid carcinoma (ATC) and medullar thyroid carcinoma
(MTC), respectively.
Table 1: The baseline features of the study groups
Association of Diabetes with Thyroid Cancer
There was a statistically significant association between
TC and diabetes. The risk of TC in diabetic patients was
3.96, CI 95%:1.98-7.95, p<0.001. There was a significant
association between TC and sex that risk of TC in female
was 3-fold male patients (OR: 3.26, CI 95%=2.07-5.11,
p<0.001). The risk of TC in the age group 60 years and
older was 7.28 (CI 95%=3.83-13.84, p<0.001) as compared
with younger individuals. After adjustment of age
and sex (multivariate logistic regression), the risk of TC
was 4.42 (CI 95%: 2.04?9.57, p<0.001).
Association of ABO Blood Group with Thyroid
Cancer
The most common blood group was blood type O
in both groups (34.5% in case and 35.6% in the control
group). Blood type A was significantly associated
with a lower risk of TC (OR: 0.57, CI 95%: 0.33 -0.97,
p=0.04). Non-significant increased risk of 60% was detected
in the patients with blood type B (Table 2).
Table 2: Results of the Univariate and Multivariate logistic regression for risk of thyroid cancer
Comparison of PTC and Non-PTC
Table 3 shows that the proportion of diabetes in the patients
with PTC was significantly higher than non-PTC patients (OR: 4.28; CI 95%: 2.02- 9.05; p=0.001). The
risk of PTC was higher in patients less than 60 years
(p=0.038). The blood type O (33.8%) and B (42.1%)
were the most abundant type in patients with PTC and
non-PTC, respectively (Table 3). There was no significant
relationship between PTC and ABO blood group
(p=0.436).
Table 3: Association between risk factors and thyroid cancer types
For the validity of the inferences, we randomly selected
175 control individuals from all control group
(two control each case) and compared and analyzed
with the case group. Its statistical results were similar
to the primary analysis and showed the significant
relationship between diabetes and TC after adjusting
other variables that findings were mentioned in a Supplementary
Table 1.
Supplementary Table 1: Results of the Univariate and Multivariate logistic regression for risk of thyroid cancer
Discussion
Our study was a retrospective study about the association
TC with the potential risk factors, including diabetes
and the ABO blood group. We used the control
group with high sample that were selected with the
same period and geographical areas of the case group.
To control confounding variables of sex and age, we
used multivariate unconditional logistic regression.
We found type 2 diabetes as an independent risk
factor for TC. This relationship was statistical significance
in female patients. Our findings were consistent
with Hemminki et al.'s and Tulinins et al." study.[,]
Chodiac et al. and Aschebrook et al. have found no this
relationship.[,] Yohwan et al. conducted a pooled analysis in 2014 and found a significant relative risk
between TC and DM; that analysis was significantly
found in female patients.[] Li et al., in 2017, tried
to use cohort studies for analysis, and they reached to
significant risk with lower heterogeneity than the Yohwan
study.[] Both pooled studies were found on
significant relative risk in male patients in similar to
our study. Those were not reached a definite conclusion
about the Asian population due to a few primary studies
(only three articles) from Asian countries.
What is for certain that the occurrence of non-communicable
diseases, such as diabetes and cancers, can
be different in worldwide because of various ethnicity,
environmental factors and lifestyle. Thus, we think this
study can be a sample of the Middle Eastern countries.
The incidence of thyroid cancer is related to multiple
factors, including modified and unmodified factors.
Diabetes type 2 is a known risk factor for some cardiovascular diseases and cerebrovascular diseases; also it
can be a potential risk factor for cancers. The mechanism
of carcinogenic of diabetes is not clear on thyroid
cancer. The proposed theories consisted of thyroid cell
proliferation, and decreased apoptosis may be due to
insulin resistance, higher body mass index (BMI), the
long-term elevation of TSH, or use of insulin-enhancing
drugs.[] Some studies have also observed a high
risk of thyroid nodules in diabetic patients [,,]
that those can be a point for thyroid cancer. In a variety
of thyroid cancers, such as papillary thyroid cancer and
anaplastic thyroid cancer, diabetes is mentioned as a
risk factor.[,] Based on our findings, it is necessary
to be considered thyroid cancer in diabetic patients, especially
female patients.
For the addition of diabetes, we studied the role of
the ABO blood group on TC. Some evidence was recently
proposed about the relationship of blood groups with some diseases like cancers. For example, it can
be noticed to the association of stomach and pancreas
cancer with blood group A.[,] The blood group O
was found a poor prognostic factor in the patients with
laryngeal cancer and also reported it a protective factor
in the patients with nasopharyngeal carcinoma.[,]
However, according to the reports, we paid attention to
this issue and reached interesting findings. Our findings
were similar to Gong et al. study and a significant
negative relationship between TC and blood type A [],
that the patients with blood type A, after adjusting age,
sex and diabetes have a 43% reduced risk of TC. Also,
we found an increased risk of 60% in the patients with
blood type B. Statistically, the risk of blood type B was
not significant but had a narrow and borderline confidence
interval. Some studies were showed a significant
relationship between TC and blood type B.[-] Thus,
our finding was non-negligible and may be due to the
small sample size of the case group.
Limitations
The findings obtained in this study are limited to the
small size of case group and incomplete data of medical
records, such as body mass index, duration of diabetes,
type of diabetes medications and thyroid stimulation
hormone level. However, this study recommended
prospective research with measured mentioned confounders.
Conclusion
Our study suggests that thyroid cancer may be associated
with diabetes and the ABO blood group. Diabetes
as a modified risk factor can be considered a starting
point for screening cancer in diabetic patients, especially
female patients.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors declare that there is no
conflict of interest for the publication of this study.
Ethics Committee Approval: This study was approved by
the medical ethics committee of Shahid Beheshti University
of medical sciences.
Financial Support: This research was supported by
Shahid Beheshti University of Medical Sciences (IR. SBMU.
REC.1396.94).
Authorship contributions: Concept - S.K., A.A.P., M.O.,
H.P., A.R.; Design - M.O., S.K., A.R., H.P., A.A.P.; Supervision
- A.A.P., S.K., H.P., A.R., M.O.; Funding - A.R., A.A.P.;
Materials - S.K., H.P., A.R.; Data collection and/or processing - M.O., A.R.; Data analysis and/or interpretation - S.K.,
A.A.P., H.P., M.O.; Literature search - M.O., S.K.; Writing -
M.O., H.P.; Critical review - H.P., M.O., S.K., A.A.P., A.R.
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