Prevalence of vitamin D deficiency in early-diagnosed cancer patients: A cross-sectional study

Abstract

Background Vitamin D roles in human health and wellbeing have been extensively studied in recent years. It has essential roles in homeostasis and maintaining many physiological functions. These roles are vital in the immune system, respiratory system, cardiovascular system, and reproductive system. Deficiency in this vitamin has been correlated with many diseases in the body, and it has been correlated with developing cancer.
Objective This study aimed to investigate levels of total vitamin D (25-hydroxycholecalciferol) in cancer patients.
Design Retrospective.
Settings: Taif city- King Faisal Hospital (KFH)
Patients and methods: serum levels of 25-hydroxycholecalciferol were classified into normal, insufficient, and deficiency group, patients were grouped according to these classes.156 patients were included in this study, 128 females and 28 males, 100 healthy participants were included. Cancer patients were as follows, gastrointest tumors patients were 27, breast cancer patients were 73, female genital tract patients were 43, head and neck cancer patients were 6 and respiratory tract patients were 7.
Sample size: 256 participants were 100 healthy controls and 156 cancer patients
Results Deficiency was detected in most of the patients from both genders and in both pre- and post-menopausal female patients.

Full text

54 Annals of Cancer Research and Therapy Vol. 28 No. 2, 2020
Ann. Cancer Res. Ther. Vol. 28, No. 2, pp. 54-59, 2020
Introduction
The reduction in vitamin D concentration has been
correlated with several disorders in the last decades,
studies have found that deciency of vitamin D is related
to the development of many acute and chronic disorders,
for instance deciency of vitamin D lead to inadequate
calcium and phosphate quantities and leading to second-
ary hypothyroidism1-3). This vitamin is naturally available
in some types of food and prescribed as a supplement
to those with deciency. It is a fat-soluble vitamin found
in two forms, D2 (ergocalciferol) which can be obtained
from nutrients like sea-food and vegetables, the other
form is D3 (cholecalciferol) that has longer half-life and
present in dairy products, also can be formed internally
by exposure to ultraviolet light, which stimulate D3 for-
mation under the skin, the later type constitute most
of vitamin D produced in the body1-4). Vitamin D rule
against infection were detected centuries ago, histori-
cally tuberculosis patients were treated by exposure to
sun-light to enhance eradication of the infection before
the discovery of vitamin D and antibiotics5, 6). Presence
of vitamin D in food is scarce, it can be found in fatty-
sh, beef liver, cheese, egg, mushrooms, and milk. Dairy
products if fortied can have measured amount of vita-
min D for daily requirement7). Following formation of
both types of vitamin D in the body, it is metabolized in
the liver and further hydroxylated in other tissues like
kidneys and breast cells to become the most effective
Prevalence of vitamin D deficiency in early-diagnosed cancer patients:
A cross-sectional study
Mazen Almehmadi1), Khalid Alzahrani1), Magdi M. Salih1), Abdulaziz Alsharif1) , Naif Alsiwiehri1),
Alaa Shafie1), Abdulraheem A. Almalki1), Ayman Alhazmi1), Haytham Dahlawi1),
Mohammed S. Alharthi1), Mustafa Halawi2), Abdulrhman M. Almehmadi3), Hatem H. Allam4)
1) Department of Clinical Laboratory Sciences, faculty of Applied Medical Sciences, Taif University, Taif city, Saudi Arabia
2) Faculty of Applied Medical Sciences, Jizan Universit y, Jizan city, Saudi Arabia
3) Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
4) Department of Physical Therapy, faculty of Applied Medical Sciences, Taif University, Taif city, Saudi Arabia
Abstract
Background: Vitamin D roles in human health and wellbeing have been extensively studied in the recent years. It has
essential roles in homeostasis and maintaining many physiological functions. These roles are vital in immune system, respi-
ratory system, cardiovascular system, and reproductive system. Deficiency in this vitam in has been correlated with many
diseases in the body, and it has been correlated with developing cancer.
Objective: This study aimed to investigate levels of total vitamin D (25-hydroxycholecalciferol) in cancer patients.
Design: Retrospective.
Settings: Taif city- king Faisal Hospital (KFH).
Patients and methods: Serum levels of 25-hydroxycholecalciferol were classified into normal, insufficient, and deficiency
group, patients were grouped according to these classes.156 patients were included in this study, 128 females and 28 males,
100 healthy participants were included. Cancer patients were as follows, gastrointestinal tract cancer patients were 27, breast
cancer patients were 73, female genital tract patients were 43, head and neck cancer patients were 6 and respiratory tract
patients were 7.
Sample size: 256 participants were 100 healthy controls and 156 cancer patients.
Results: Deficiency was detected in most of the patients from both genders, and in both pre- and post-menopausal female
patients.
Conclusion: These findings support the belief that deficiency in vitamin D is a risk factor leading to development of cancer.
Keywords: Vitamin D (25-hydroxycholecalciferol), breast cancer, gastrointestinal tract cancers, female genital tract cancers,
respiratory tract cancers, head and neck cancer, menopause.
(Received June 18, 2020; Accepted June 26, 2020)
Corresponding author: Dr. Maze n Almehmadi, Depa rtm ent of Clinical L abor ator y
Scien ces, facul ty of A pplied Medical Scie nces, Taif Universit y, Taif cit y, Saudi Arabia.
E-mail: Dr.mazen.ma@gmail.com Mazenn@tu.edu.sa

55
Vitami n D deficiency i n Cancer Pa tient s
form 1,25-hydroxy vitamin D the ligand for vitamin D
receptor (VDR), furthermore, polymorphisms in VDR
have been associated with obesity and breast cancer8, 9).
Moreover, binding of vitamin D and its metabolites to
VDR can manifest vitamin D physiological effect10, 11) .
The concentration of vitamin D in the serum should be
monitored regularly, as several factors can affect vitamin
D amount, for example less exposure to sun light can af-
fect D3 formation which is the predominate endogenous
formed vitamin D, and malnutrition or consumption of
vitamin D free diet12). Immune system surveillance is es-
sential to kill cancerous cells, patients with low vitamin
D levels were exposed to high number of respiratory tract
infection, autoimmune diseases, and development of sev-
eral types of cancer1, 13 -16).
The aim of this study was to investigate the preva-
lence of vitamin D deciency in early-diagnosed cancer
patients, also to evaluate the levels between patients age
groups, and pre-menopausal female versus menopausal.
The outcomes of this study can help to assess the prob-
ability of developing cancer due to vitamin D deciency.
Materials and Methods
Study design
This retrospective cross-sectional study was approved
by the directorate of health affairs in Taif city, IRN reg-
istration number HAP-02-T-067 for the period 2018 to
May 2020, a consent form was provided prior using of
data. All recruits in this study have to meet the following
strict inclusion criteria to be included, rstly; diagnosed
with any type of cancer at KFH between 2018 and 2020;
secondly; only early-diagnosed cancer patients were in-
cluded and patients who were previously diagnosed were
excluded; thirdly; have not taken vitamin D supplement
for at least 60 days and had measurement of vitamin D
total (25-hydroxycholecalciferol) when they provided a
biopsy sample to laboratory. The study aimed to obtain a
total of 200 participants which are 100 patients and 100
healthy controls, however, the total number of partici-
pants reached 256 as follows 156 patients that have satis-
fied this study strict inclusion criteria, and 100 healthy
participants were included free from cancer and debili-
tating disorders.
Sample analysis
When patients were requested to provide biopsy
sample according to physician request, minimum of 3
mL of venous blood were collected into plain tube, ana-
lyzed freshly and not stored through ROCHE COBAS®
platform e501. Patients were advised to fast for 10 hours
prior collecting of the blood as the sample was used to
diagnose other tests including vitamin D. This study
has collected the following information, sex, age of the
patient, type of diagnosed cancer, levels of vitamin D.
Vitamin D serum levels was categorized into three dif-
ferent categories, normal level for those who were ≥50
ng\mL, insufciency for those who were 30 to 49 ng\mL
and deciency for those who were ≤29 ng\mL.
Statistical analysis
Microsoft excel for ofce was used for sorting of data,
calculating frequencies, percentage, chi-square analysis
and standard deviation (σ), Pearson’s chi-square test was
used to detect any signicant frequency in a single cat-
egory. For odds ratio (OR), relative risk (RR) and 95%
condence interval (95% CI) medcal-website were used
(www.medcalc.org), results when P value <0.05 were
considered signicant.
Results
Demographic analysis
This study has included 156 cases of early-diagnosed
cancer patients (Table 1) and satised the strict inclusion
criteria. Number of female cases was 128 and constitutes
82% of the study group, and number of male cases was
28 and constitutes 18% of the study group. Most of the
cases were females for the age group 40–64 years which
were 52% of total cases.
Types of cancer
After sorting of data of this study, the categories of
cancer types are arranged as follows, breast cancer, re-
spiratory tract cancer, head and neck cancer, and gastro-
intestinal tract cancer, and female genital tract cancer.
The frequencies of these types are illustrated in Table 2.
Prevalence of Vitamin D deciency
Analysis of the prevalence of vitamin D deficiency
was assessed according to levels of the serum vitamin
D into 3 groups normal, insufficient, and deficiency.
Characteristics analyzed were age, sex, and menopausal
status of female patients (Table 3) and according to type
of cancer in (Table 4). Mean of vitamin D was higher
in males than females for both healthy and patients. In
males, mean levels were higher in healthy than patients
(OR 2.95 and RR 2.0115) indicating increase frequency
in patients than healthy of vitamin D deficiency. In fe-
males, same results were detected as mean levels were
higher in healthy than patients (OR 1.26 and RR 1.118)
indicating also high frequency in patients than healthy of
vitamin D deficiency. Comparing levels by age showed
high frequency and prevalence of cancer with vitamin
D deficiency in ≤39 years, and higher mean levels in
healthy than patients and high prevalence of vitamin D
deficiency among patients (OR 17 and RR 3.4) as most
of the healthy were in insufcient groups while patients
were mostly having vitamin D deficiency. For 40 to 64
years mean levels were higher in healthy than patients

56 Annals of Cancer Research and Therapy Vol. 28 No. 2, 2020
Table 2 Types of cancer included in this study according to sex,
tissue type, diagnosis, and frequencies.
Sex Tissue Cancer type n cases
Percentage
%
Male Gastrointestinal
tract
Sigmoid 10 35.7
Caecum 13.5
Ascending colon 13.5
Descending colon 13.5
Rectal mass 517. 8
Colon mass, Rectum polyp 310.7
Gastric and liver tumor 13.5
Head and Neck Nasopharyngeal carcinoma 13.5
Respiratory tract Lung 13.5
Nose 414. 28
Fema le Breast cancer Invasive Duct Carcinoma 55 42.18
Invasive Lobular
Carcinoma
9 7
Invasive micropapillary
carcinoma
10.78
Mucinous adenocarcinoma 10.78
Invasive pleomorphic
lobular carcinoma
10.78
Invasive mammary
carcinoma
10.78
Infiltrating lobular
carcinoma
10.78
Infiltrating Duct carcinoma 10.78
Solid papillary carcinoma
breast
21.5 62 5
In situ duct carcinoma 21.5 62 5
Female Genital
tract
Endometrial cancer 26 20.31
Cervical cancer 11 8.59
Anterior vaginal wall 10.78
Uterus, cerv ix, and fallopian
tube
32.34
Ovaria n cyst 10.78
Uterine carcinoma 10.78
Head and Neck Tongue carcinoma 10.78
Thyroid 53.9
Respiratory tract Bronchus 10.78
Gastrointestinal
tract
Tubulovillous Adenoma 20.78
Rectal mass 10.78
Esophagea l 11.56
Total 156
Table 3 Evaluation of serum levels of vitamin D between healthy and cancer patients according sex, age and menopause status.
Characteristics
Serum level
Vit-D
ng\mL (σ)
Normal
≥ 50
insufficiency
30– 49
Deficiency
≤ 29 P value Odds ratio
(P-value, CI 95%)
Relative risk
(P-value, CI 95%)
Sex
Males Patients 30. 51 (12. 49) 2 (7.15%) 13 (46.42%) 14 (45.78%) 0.01328 2.9
(0.0295, 1.1142 to 7.84)
2. 0115
(0.02734, 1.0813 to 3.7417)
Healthy 38.6 8 (14.03) 8 (16%) 30 (60%) 12 (24%) 0. 0162 4
Fema le s Patients 29.4 (1 2. 51) 10 (7.8%) 44 (34.37%) 74 (57.8%) 0.00000 1.2 6
(0.4828, 0.6561 to 2.4387)
1.118
(0.4945, 0.8198 to 1.5)
Healthy 33 (13.6) 4 (8%) 20 (40%) 26 (52%) 0.0 20 65
Age groups
≤ 39 Patients 23.02 (13.7 ) 1 (5%) 2 (10%) 17 (85%) 0.00001 17
(0.009, 3.202 to 90.25)
3.4
(0.0057, 1.4267 to 8.1)
Healthy 38.625 (16.06) 2 (12.5%) 10 (62. 5%) 4 (25%) 0.19691
40–64 Patients 30. 03 (12.52) 8 (8.5%) 34 (36.17%) 52 (55.22%) 0.00000 1.96
(0.0434, 1.0202 to 3.766)
1.4291
(0.0533, 0.995 to 2.05)
Healthy 35.96 (14.34) 8 (13%) 30 (48.4%) 24 (3.6%) 0. 04751
≥ 65 Patients 31.81 (10.81) 3 (6.9%) 20 (46.51%) 20 (46.59%) 0.0 0121 1. 0435
(0.9355, 0. 3721 t o 2.926 4)
1.0 233
(0.9503, 0.585 to 1.789)
Healthy 33. 45 (12.17) 2 (9%) 10 (45.5%) 10 (45.5%) 0.233 51
Menopause
Post Patients 29.75 (11.65 ) 7 (8.1%) 31 (36.04%) 48 (55.8%) 0.00042 4
(0.0001, 2.14 to 7.5)
0.8 421
(0.0743, 0.7 to 1.017)
Healthy 24. 25 (8. 46) 06 (25%) 18 (75%) 0.00003
Pre Patients 28.67 (14.2) 3 (7.14%) 13 (30.9%) 26 (61.89%) 0.00007 5.14
(0.0001, 2.374 to 11.15)
1.4 4
(0.725, 0.97 to 2.15)
Healthy 34.38 (14.11) 2 (8%) 14 (53.5%) 10 (38.5%) 0. 013 46
Table 1 Demographic analysis of the study
including sex, frequency, mean and σ.
Number of
cases Mean χ σ
Sex Male 28 patients
50 healthy
62 15.4
Fema le 128 patients
50 healthy
56.23 13. 86
Age ≤ 39 Male 434 7. 14
Fema le 32 34 3. 5
40–64 Male 41 57. 8 5. 8
Fema le 115 53.66 6.5
≥ 65 Male 33 7 7. 3 6 6.4
Fema le 31 74.41 8. 3
Total 256

57
Vitami n D deficiency i n Cancer Pa tient s
and most patients showed vitamin D deficiency, and
healthy having insufciency of vitamin D (OR 1.96 and
RR 1.4291). And for more than 64 years mean levels were
higher in healthy than patients, and equal percentage of
patients in insufficient and deficient group (OR 1.0435
and RR 1.0233) but with insignicant P value. Prevalence
of vitamin D deciency in females were further studied
according to menopause state, and high prevalence of
vitamin D deciency in postmenopausal females in both
healthy and patients (OR 4 and RR 0.8421), also in pre-
menopausal females patients were highly having vitamin
D deciency and healthy mostly having insufcient vita-
min D (OR 5.14 and RR 1.44).
For gastrointestinal tract cancer patients, high preva-
lence of vitamin D deciency was detected (OR 3.41 and
RR 0.6823), and sigmoid cancer patients have shown high
prevalence of vitamin D deciency (OR 3.17 and 0.6679).
In head and neck high frequency of vitamin D deciency
detected (OR 7.9 and RR 0.9398). Also, in respiratory
tract patients (OR 3.17 and RR 0.65). In breast cancer pa-
tients all cases were females and high prevalence of vita-
min D deciency was detected (OR 3.51 and RR 0.6925),
moreover, those with invasive duct carcinoma having
high frequency of vitamin D deciency than the rest of
breast cancer patients (OR 3.55 and RR 0.69). In female
genital tract cancer patients, no normal level of vitamin
D was detected among all the 43 participants, most of
the patients having vitamin D deciency (OR 6.1 and RR
0.87), the same was detected in endometrial cancer (OR
5.07 and RR 0.8097), among cervical cancer patients
high prevalence was detected of vitamin D deciency (OR
8.5 and RR 0.95).
Discussion and Conclusion
This study aimed to investigate the prevalence of
vitamin D deficiency among early-diagnosed cancer
patients between 2018 to May 2020. 156 patients were
recruited into this study, shared between 28 males and
128 females. The serum level of vitamin D was classied
into three groups, the objective of this classication was
to investigate the variation of serum vitamin D levels.
Vitamin D deciency is clearly detected in most of this
study patients, obviously most of patients’ groups have
deciency of vitamin D (Table 3 and 4).
Vitamin D is effective against cancer prevention,
and deficiency in vitamin D have been associated with
several diseases1, 4, 7, 15), which explain the results of this
study. However, an inconsistent study to ours and the rest
have stated that cancer is more prevalent in vitamin D
sufcient than deciency group1, 4, 7, 15-18). In this study, an
association was clear between vitamin D deciency and
different types of cancer. High percentage of gastrointes-
tinal tract cancer patients have vitamin D deciency (OR
3.41, 95% CI 1.4 to 8.25) which is consistent with several
studies established this point19). Several studies have
stated that vitamin D deciency is a risk sign of develop-
ing breast cancer, and another study have stated that most
of their study group were vitamin D deficient which is
consistent to our ndings (OR 3.51, 95% CI 1.85 to 6.7)5,
8, 20). Invasive duct carcinoma was the common type of
breast cancer in our study, and 53.7% (OR 3.55, 95% CI
1.75 to 7.2) of those patients already have vitamin D de-
ciency. Female genital tract patients also showed vitamin
Table 4 Evaluation of serum levels of vitamin D between cancer patients according to different characteristics (All; all patients).
Characteristics
Serum level
Vit-D
ng\mL (σ)
Normal
≥ 50
insuffi-
ciency
30– 49
Deficiency
≤ 29 P value Odds ratio
(P-value, CI 95%)
Relative risk
(P-value, CI 95%)
Type of cancer
Gastrointestinal
tract
All 27.81 (13. 63) 2 (7.4%) 11 (40.74%) 14 (51.85%) 0.01312 3. 41
(0.0065, 1.4 to 8.25)
0.682 3
(0.0485, 0. 46 67 to 0.9975)
Sigmoid 2 9. 4 (1 3. 68 ) 1 (10%) 4 (40%) 5 (50%) 0.00022 3.17
(0.087, 0.85 to 11.9)
0.6679
(0.1924, 0.35 to 1.23)
Head and neck 25 (10.23) 02 (28.57%) 5 (71.42%) 0.06625 7.9
(0.0172, 1.44 to 43.45)
0.9398
(0.8006, 5808 to 1.5209)
Respiratory
tract 34.5 (1 0.71) 03 (50%) 3 (50%) 0.22 313 3.17
(0.175, 0.6 to 16.7)
0.65
(0.2096, 0.2933 to 1.475)
Breast cancer
All 31.5 7 (14 ) 10 (13.15%) 26 (34.21%) 40 (52.6%) 0.00014 3.51
(0.0001, 1.85 to 6.7)
0.6925
(0.0 027, 0. 5447 to 0.88 04)
Invasive duct
carcinoma 31. 5 (14.2 4) 8 (14.8%) 17 (31.5%) 28 (53.7%) 0.00 21 3.55
(0.0005, 1.75 to 7.2)
0.69
(0.0101, 0.52 7 to 0.9172)
Invasive
lobular
carcinoma
40.4 4 (14.9) 3 (33. 33%) 4 (44.44%) 3 (33.33%) 0.9048 4 1.357
(0.6752, 0.325 to 5.66)
0.4
(0.0559, 0.1522 to 1.0239)
Female genital
tract
All 26.49 (8.79) 014 (3 4.14%) 27 (65.81%) 0.00001 6.1
(>0.0001, 2.76 to 13.5)
0.87
(0.2542, 0.677 to 1.1086)
Endometrial
carcinoma 2 7. 61 (8. 5) 010 (38. 5%) 16 (61. 5%) 0.00053 5.0 7
(0.0005, 2.03 to 12.63)
0.80 97
(0.2006, 5861 to 1.1187)
Cervical
cancer 23.75 (9. 99 ) 03 (27.27%) 8 (72.72%) 0. 0116 3 8.5
(0.0029, 2.07 to 34.4)
0.95
(0.812, 0.66 to 1.4)

58 Annals of Cancer Research and Therapy Vol. 28 No. 2, 2020
D deciency (OR 6.1, 95% CI 2.76 to 13.5), and further
analysis of cervical cancer (OR 8.5, 95% CI 2.07 to 34.4)
and endometrial cancer patients (OR 5.07, 95% CI 2.03
to 12.63) have showed the same feature. For endometrial
cancers a study have showed no relation between serum
levels of vitamin D and developing endometrial cancer
which contrast our nding21) . In cervical cancer, accord-
ing to many studies is developed due to human papilloma
virus (HPV) infection and lack of knowledge is estab-
lished, cervical cancer is common in patients who have
showed low levels of vitamin D, these nding can suggest
that deciency of this vitamin can weaken the immune
response leading to HPV infection and development of
cancer due to HPV22-24).
Vitamin D deficiency can lead to several health
complications which can increase in post-menopausal
females2). Mean of serum vitamin D in post-menopausal
female was 29.75 (11.86) and pre-menopausal was 28.67
(14.2) which almost equivalent, both show deciency in
vitamin D and this finding contrast other study stated
postmenopausal have higher levels of vitamin D more-
over, both groups have more patients with deciency in
vitamin D. Several studies have detected cancer even
with supplementation of vitamin D in breast cancer pa-
tients2- 4, 20).
In conclusion, this study has detected high prevalence
of vitamin D deciency among different cancer patients.
This study revealed high prevalence of vitamin D defi-
ciency with high OR which associate between the fre-
quency and developing cancer. According to many previ-
ous studies, this deficiency is common among healthy
and patients, however, in healthy people if not maintained
by improving diet, absorbing sun light, practicing sport
and prescribing high-quality supplements of vitamin
D can impact health and lead to several complications.
Promoting and providing health education have helped
in increasing knowledge of the importance of vitamin D.
Screening among public should be performed to all age
groups especially that show signs of deciency. Due to its
essential role in maintain healthy body, healthy immune
system, and regulating many other functions in the body.
Acknowledgement:
The authors would like to thank the deanship of scientific re -
search for their nancial support for this project (project no. 1-440-
6143). And than ks to all medical sta ff in king Faisal hospital and
everyone participates in this study, many thanks to Mrs. Ashwaq
Alkhaldi and M rs Ashwaq Altalhi.
Conict of interest: No ne.
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