Association of leptin -2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer.
OBJECTIVE
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.
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Kifissias and Perikleous Stavrou 9, 11524, Athens, Greece.
Christos
C
Yapijakis
Michael
M
Kechagiadakis
Emeka
E
Nkenke
Zoe
Z
Serefoglou
Dimitrios
D
Avgoustidis
Antonis
A
Vylliotis
Despina
D
Perrea
Friedrich W
FW
Neukam
Efstratios
E
Patsouris
Eleftherios
E
Vairaktaris
D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005858:Germany; D006115:Greece; D006720:Homozygote; D006801:Humans; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008487:Medical History Taking; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors
D017931:DNA Primers; D020738:Leptin; D054411:Receptors, Leptin