There significant weakly positive associations [24-26] and even inverse

There are various studies showing association of cancers and serum
glycosylated hemoglobin (HbA1c)..However, the number of studies investigating the association between lung cancer
and HbA1c are limited.

Our study
indicates that there may be an increased cancer risk  associated with HbA1c levels ‡6%, i.e.in
those with moderately elevated  HbA1c
levels (6%–6.9%), -which is below the accepted guidelines for the diagnosis of
diabetes.

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It is also
possible that hyperglycemia and hyperinsulinemia together may contribute to the
association between type 2 diabetes and cancer through the following
mechanisms:

 

·       
Glucose, through its action on
production of insulin and insulin-like growth factor (IGF)-I may enhance tumor
development by stimulating cell proliferation and by inhibiting apoptosis 15,
16.

 

·       
Insulin enhances the stimulatory effects
of growth hormone on IGF-I synthesis, and also increases IGF-I bioactivity by
down-regulating the synthesis of IGF-binding proteins-1 and -2 17.

 

·       
Both insulin and IGF-I are involved in
the synthesis and circulating levels of sex steroids and sex hormone-binding
globulin and thus may also specifically increase the risk of hormone-responsive
cancers such as breast and endometrial cancers 17.

 

 

Several
prospective studies support the role of IGF-I on the development of prostate
18, 19, colorectal 20, 21 and premenopausal breast 22, 23 cancers in
particular.

The
significantly increased risk for respiratory cancers observed among the subjects
having elevated glucose levels was slightly unexpected, since previous studies
reporting results on diabetes and/or impaired glucose tolerance and lung cancer
have indicated only non significant weakly positive associations 24-26 and
even  inverse associations 27,28. Our
findings are unlikely to be explained by tobacco smoking, as the analyses based
on nonsmokers showed similar results. The increased risk observed may be due to
elevated levels of IGF-I, as Yu et al. 29 previously reported a strong positive
association between circulating IGF-I and lung cancer.

 

However, the
findings presented here should be interpreted with caution, since our study has
several limitations:

·       
The main limitation of this study is the
lack of anthropometric data. As being overweight is a known risk factor for
both impaired glucose tolerance and diabetes as well as for several cancers,
the increased risks observed for these cancers may be due to excess body weight
or obesity rather than elevated glucose levels per se.

 

·       
The short follow-up time is a second
limitation of this study, because with such a short time interval between HbA1C
estimation and diagnosis of malignancy, we could not restrict the analyses to
the cases diagnosed at least 2 years after the HbA1c test to eliminate subjects
with undetected disease at the time of the blood test. Therefore, we could not
exclude the possibility that undiagnosed cancer at the time of the HbA1c test
might have led to elevated glucose levels.

·       
Finally, the small sample size limited the
power for analyses by cancer sub types.

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