METHODS
Blood drawn from patients with VTE (n=45) and from patients without VTE (non-VTE; n=23), as a
control group without a history of VTE, and SHBG levels were compared between groups.
RESULTS
There was no difference in SHBG levels between VTE (59.7±41.5) and non-VTE (60±49) (p=0.71)
group, but gastric cancer patients had statistically higher SHBG levels (73.7±39.9; range from 36.6 to
176.2 ) than rest of the cohort (56.54±44.4; range from 9.6 to 246.6) (p=0.033), although it was out of
scope of this study.
CONCLUSION
Although our study did not show any impact of SHBG levels on risk of VTE at patients with advanced
stage adenocarcinoma, it revealed high levels of SHBG at gastric cancer patients which deserve further
research.
Keywords: Adenocarcinoma; sex hormone-binding globulin; venous thromboembolism
SHBG can be easily and rapidly measured in routine laboratories and may be useful to asses prothrombotic profile and further validation with more studies as biomarker in gastric cancer. Assuming SHBG as surrogate marker for hormonal stimulus as an increasing risk factor for VTE, we herein sought to elucidate if background SHBG has any impact on VTE in patient with advanced stage adenocarcinoma.
SHBG levels were compared between groups. All the laboratory analyses held in the Department of Biochemistry, Haseki Research and Training Hospital. The study protocol approved by the Local Ethics Committee of Haseki Research and Training Hospital, and written informed consent was obtained from all patients before inclusion into the study. The study granted by Tez ve Akademik Calısmalar Danısma ve Izleme Komisyonu, which is research support organization of Haseki Research and Training Hospital.
Assay of SHBG
Venous blood samples were collected in tubes from
the antecubital vein, followed by overnight fasting. The
tubes were centrifuged at 4000 rpm (10 min) to remove
the serum. The serum samples were stored at -80°C until
analysis SHBG. We used in vitro diagnostic reagent
for the quantitative determination of SHBG in human
serum by means of chemiluminescent immunoassay
on Beckman Coulter Access Systems. (Beckman
Coulter, Inc., 250 S. Kraemer Blvd., Brea, CA 92821
U.S.A.). The access SHBG assay is a sequential twostep
immunoenzymatic ("sandwich") assay. A sample
is added to a reaction vessel along with paramagnetic
particles coated with monoclonal anti-SHBG antibody
and saline buffer with proteins. After incubation in a
reaction vessel, materials bound to the solid phase are
held in a magnetic field while unbound materials are
washed away. A second monoclonal anti-SHBG antibody
conjugated to alkaline phosphatase is added to
the reaction vessel. After the second incubation in the
reaction vessel, materials bound to the solid phase are
held in a magnetic field while unbound materials are
washed away. Then, the chemiluminescent substrate
Lumi-Phos* 530 is added to the vessel and light generated
by the reaction is measured with a luminometer.
The light production is directly proportional to the
concentration of SHBG in the sample. The amount of
analyte in the sample is determined from a stored, multipoint
calibration curve. Reference unit was nmol/L.
Statistical Analysis
Descriptive statistics were reported as percentages and
medians with standard deviations. The Chi-square test
was used for the comparison of categorical variables. Student's
t-test and Mann-Whitney U-test were used for the
comparison of means. P<0.05 was considered statistically
significant. Statistical analyses were performed with the
use of SPSS version 17 (SPSS Inc., Chicago, Illinois, USA).
Our results demonstrated that SHBG did not differ
in patients with adenocarcinoma with VTE and without
VTE indicating that hormonal stimulus or background
hormonal milieu did not have any impact on
increased risk of VTE in patient with advanced stage
adenocarcinoma. The plasma levels of SHBG are the
sum of multiple stimulatory and inhibitory factors.
Women show decreasing level of SHBG between the
second and sixth decades followed by a steady increase
at around 60 years, a U-shaped trajectory, whereas
men show an increasing levels with age.[
Tissue factor (TF) expression by cancer cells, which
is the most likely explanation of procoagulant activity
in cancer patients, is shown to be started at early stages
carcinogenesis with the activation of MET oncogene.
[
In a recent study by Cheng et al.,[
Although to the best of our knowledge, this is the
first study sought to elaborate relationship between
SGBG and thrombosis in adenocarcinoma, retrospective
nature of study inherent limitations. We are aware
and acknowledge that caution required interpreting results
when a candidate surrogate marker like SHBG is
studied, as they can be severely misleading, hence, its
levels are affected by many dependent end independent
factors. One other limitation of our study relates to the
relatively small population sample.
In conclusion, SHBG levels were not different in
cancer patients with VTE compared to controls without
VTE. Our study cannot totally exclude the possible
association between VTE and SHBG levels in gastric
cancer.
Acknowledgment: The author thanks to the sponsor of
the study, Tez ve Akademik Calismalar Danisma ve Izleme
Komisyonu (TACDIC), which is research support organization
of Haseki Research and Training Hospital.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by
The Haseki Research and Training Hospital Ethics Committee
(No: 2, Date: 20/05/2013).
Financial Support: This study has received financial support
from Tez ve Akademik Calismalar Danisma ve Izleme
Komisyonu (TACDIC), which is research support organization
of Haseki Research and Training Hospital.
