19 research outputs found
Oral squamous cell cancer: early detection and the role of alcohol and smoking
Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved
High frequency of TTTY2-like gene-related deletions in patients with idiopathic oligozoospermia and azoospermia
Genes located on Y chromosome and expressed in testis are likely to be
involved in spermatogenesis. TTTY2 is a Y-linked multicopy gene family
of unknown function that includes TTTY2L2A and TTTY2L12A at Yq11 and
Yp11 loci respectively. Using PCR amplification, we screened for
TTTY2L2A- and TTTY2L12A-associated deletions, in 94 Greek men with
fertility problems. Patients were divided into three groups as
following: group A (n=28) included men with idiopathic moderate
oligozoospermia, group B (n=34) with idiopathic severe oligozoospermia
and azoospermia, and group C (n=32) with oligo- and azoospermia of
various known etiologies. No deletions were detected in group C patients
and 50 fertile controls. However, two patients from group A had
deletions in TTTY2L2A (7.1%) and six in TTTY2L12A (21.4%), whereas
from group B, four patients had deletions in TTTY2L2A (11.8%) and 10 in
TTTY2L12A (29.4%). In addition, five patients from both groups A and B
(8%) appeared to have deletions in both studied TTTY2 genes, although
these are located very far apart. These results indicate that the TTTY2
gene family may play a significant role in spermatogenesis and suggest a
possible mechanism of nonhomologous recombinational events that may
cause genomic instability and ultimately lead to male infertility
Association of leptin -2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer
Purpose: We investigated the possible association of DNA polymorphisms -2548G/A and Q223R in the leptin (LEP) and leptin receptor (LEPR) genes, respectively, which both affect the amount of circulating cytokine-type hormone leptin, with risk for development of oral cancer. Methods: Polymerase chain reaction-based restriction analysis was performed in DNA samples of 150 patients with oral squamous cell carcinoma (OSCC) and 152 healthy control subjects of equivalent gender, age, and ethnicity (Greeks and Germans). Results: Compared to controls, the homozygous high gene expression genotype A/A of the LEP -2548G/A polymorphism was significantly increased in the subgroups of patients with advanced cancer stages (P = 0.0001; OR 9.0, 95% CI 2.62-30.89), with a positive family history of cancer (P = 0.0346; OR 3.55, 95% CI 1.15-11.01), without tobacco abuse (P = 0.0051; OR 9.69, 95% CI 1.03-91.24), and without alcohol abuse (P = 0.0472; OR 2.16, 95% CI 0.87-5.37). The homozygous low-leptin-binding genotype G/G of the LEPR Q223R polymorphism was strongly associated with an increased risk for OSCC for all patients (P = 0.0028; OR 4.11, 95% CI 1.30-12.97) as well for most of the patient subgroups. Conclusions: The above findings are consistent with the growth-promoting role of leptin in cancer and its induction effect on angiogenesis and metastasis. This is the first study indicating the association of these LEP and LEPR gene polymorphisms with increased risk for OSCC. © 2008 Springer-Verlag
Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer
Genetic association studies have implicated functional DNA polymorphisms
in genes encoding factors related to angiogenesis, inflammation and
thrombosis with increased risk for oral squamous cell carcinoma (OSCC).
This study examines possible interactions between nine such genotype
polymorphisms and their combinatory effect in assessing the OSCC risk in
a European population.
OSCC cases (N = 162) and healthy controls (N = 168) of comparable age,
gender, and ethnicity (Greeks and Germans) were studied. Multivariate
logistic regression models were constructed in order to assess the
contribution of homozygous or heterozygous variant genotypes of
polymorphisms MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A), MMP-9
(-1562C/T), TIMP-2 (-418C/G), VEGF (+936C/T), GPI-alpha (+807C/T), PAI-1
(4G/5G), ACE (intron 16D/I) and TAFI (+325C/T) upon overall, early and
advanced stages of OSCC.
Four out of nine polymorphisms affecting PAI-1, MMP-9, TIMP-2 and ACE
expression contributed significantly in OSCC prediction in the various
logistic regression models. Based on these findings and previous
reports, possible interactions of the implicated factors leading to OSCC
development, as well as an algorithm of risk estimation are discussed.
(C) 2008 Published by Elsevier Ltd
A metalloproteinase-9 polymorphism which affects its expression is associated with increased risk for oral squamous cell carcinoma
Aim: In light to recently found contribution of factors associated with
angiogenesis, thrombosis and inflammation to carcinogenesis, we
investigated the possible association of metalloproteinase-9 (MMP-9)
with increased risk of oral cancer.
Methods: In DNA samples of 152 patients with oral squamous cell
carcinoma and 162 healthy controls of comparable ethnicity, age and sex,
we studied the -1562 C/T polymorphism in the MMP-9 gene promoter, which
affects its transcription.
Results: The detected frequency for the high expression T allele in the
patients’ group was significantly increased in comparison to that of the
control group (22% versus 15%, respectively; P < 0.05). This
difference was due to the relative increase of C/T heterozygotes in the
group of patients, in comparison to controls (P < 0.05, 95% OR 1.92, CI
1.21-3.06). The same pattern of significance was observed between
controls and the subgroups of patients with initial (I & II) stages of
cancer, without positive family history of cancer or thrombophilia, with
smoking and alcohol abuse habits.
Conclusions: The investigated MMP-9 polymorphism has a strong
association with increased risk for developing oral cancer in a subset
of the general population. These results are in accordance to previous
studies of constitutive expression and secretion of MMP-9 in invasive
oral carcinoma cell lines. The observation that T allele carriers have
an increased risk for developing oral cancer only in initial stages, but
not in advanced ones, may be due to the role of MMP-9 in the inhibition
of angiogenesis by generating angiostatin from plasminogen. (C) 2007
Elsevier Ltd. All rights reserved
Plasminogen activator inhibitor-1 polymorphism is associated with increased risk for oral cancer
In light of the recently observed contribution of thrombosis-related
factors to carcinogenesis, we investigated the possible association of
plasminogen activator inhibitor-1 (PAI-1) with increased risk for oral
cancer. In DNA samples of 104 patients with oral squamous cell carcinoma
and 106 healthy controls of comparable ethnicity, age and sex, we
studied the 4G/5G polymorphism in the PAI-1 gene, which affects its
expression. The mutant 4G allele and carrier frequencies were
significantly increased in patients compared to controls (65.9% versus
49.5%; 88.5% versus 69.8% respectively, P < 0.01). That increase was
even higher in patients with a positive family history for thrombophilia
or without one for cancer (P < 0.001). Interestingly, significant
difference from controls was observed only in patients with cancer
stages I and II. These findings suggest that the 4G allele, by resulting
in higher PAI-1 expression, is a major contributing factor in early
stages of oral oncogenesis. Possibly, increased PAI-1 promotes initial
development of oral cancer through regulation of cell detachment and
delays further tumor progression by inhibiting vascularization. (c) 2006
Elsevier Ltd. All rights reserved
Association of platelet glycoprotein la polymorphism with minor increase of risk for oral cancer
Aims: In light to association of increased platelet glycoprotein la
(GPIa) expression with tumor invasion and metastasis in several types of
cancer, we investigated the possible contribution of a common
polymorphism (C-807/T-807), affecting the GPIa gene expression, in the
development of oral cancer.
Methods: DNA samples of 110 patients with oral cancer and 114 healthy
controls were examined by allele-specific polymerase chain reaction
followed by electrophoretic analysis.
Results: The mutant T-807 allele homozygotes were significantly
increased in the group of patients compared to the control group (P <
0.001). Furthermore, significantly increased frequency of mutant alleles
compared to controls was observed in the subgroup of patients with a
positive history for cancer (P<0.01).
Conclusions: The obtained results indicate that the C-807/T-807
polymorphism is indeed a genetic predisposing factor which contributes
to increased risk for oral cancer. (C) 2006 Elsevier Ltd. All rights
reserved
The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma
Aims: In light of recently found contribution of angiogenic and
inflammation-related factors to malignancies, this study investigated
the possible association of interleukin-8 gene (IL-8) to increased risk
of oral cancer.
Methods: The IL-8 (-251A/T) polymorphism, which influences IL-8 gene
expression, was evaluated by restriction fragment length polymorphism
analysis in DNA samples of 158 German and Greek patients with oral
squamous cell carcinoma and 156 healthy controls of equivalent sex,
ethnicity and age.
Results: Significant increase of mutant (A-251) allele, which results in
higher IL-8 gene expression, was observed in all patients in comparison
to normal controls (P < 0.001). The A/T heterozygotes had a two-fold
greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer
compared to normal TT homozygotes. Furthermore, significantly increased
values of mutant allele frequencies compared to controls were observed
in all patients as well as in subgroups of patients with or without
positive history of cancer (P < 0.05 and P < 0.001, respectively) and
with or without positive history of thrombophilia (P < 0.05 and P <
0.001, respectively).
Conclusions: In light to known observations of elevated plasma levels of
IL-8 in several types of cancer including oral squamous cell carcinoma,
the findings of this study suggest that the mutant allele of the
(-251A/T) polymorphism may be a major contributing genetic factor to
fisk for oral cancer. (c) 2006 Elsevier Ltd. All rights reserved
Head and Neck Squamous Cell Carcinoma in the Young: A Spectrum or a Distinct Group? Part 1
While most head and neck squamous carcinoma (HNSCC) occurs in older people, an increasing number of young patients are being affected worldwide, with up to 5.5% <40. These are predominantly oral and oropharyngeal cancers. Some patients have heavy exposure to the usual risk factors, but an increasing number do not. Part of this trend appears to be due to rising numbers of HPV associated tonsil carcinoma, particularly in males (smokers and non-smokers). A subset of young patients, however, is non-smoking females usually with tongue cancers, not related to HPV, the aetiology of which is unclear. Various mechanisms may be at work here: the variation in ability to detoxify the products of smoke and alcohol varies in individuals, which may explain why environmental exposure to smoke seems to play a role in some non-smokers with HNSCC. The role of marijuana remains possible but uncertain, and it may be that anaemia is a co-factor. There is an increased risk of HNSCC in first degree relatives of HNSCC patients, and while inherited syndromes associated with HNSCC are rare, elucidation of their genetics may help to develop our understanding the disease in these young patients without recognised risk factors