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ABSTRACT
Cancer of the upper aero-digestive tract is the sixth most common malignancy worldwide; this anatomical region includes the oral cavity, pharynx and larynx. The incidence of these tumours increases with the age: in Europe, in 98% of the patients are over 40 years of age. However, during the past decades, there has been an alarming rise in the incidence of oral cancer particularly among younger men, a trend that appears to be continuing.
In the development of cancers of oral cavity, pharynx and larynx both tobacco and alcohol consumption are well-established risk factors. These two risk factors acts independently even if their association seems to have a multiplicative effect. However persons subject to a level of comparative exposure have a higher or lower susceptibility of this tumour. A possible explanation is that some patients appear susceptible to cancer because of an inherited trait that affects their ability or inability to metabolise carcinogens or pro-carcinogens. Others have an inherited impaired ability to repair the DNA damage, since damaged cells are repaired or induced to suicide (apoptosis). Therefore the efficiency of the genes implicated in DNA repair, cell cycle control and apoptosis must be considered an important factor in establishing the risk of cancer among different persons. The aim of our study is to understand the role of these genes in modulating the individual susceptibility to this tumor. We analysed 104 DNA samples of patients affected with cancer of upper aero-digestive tract and 280 DNA samples of healthy subjects representing a general population (controls), selectively chosen with an age similar to the cases group. The samples were selected from a cohort of 1000 persons of six different countries: Poland, Russia, Slovakia, Romania, Hungary and Czech Republic. In this study we employed a genotyping microarray for 119 polymorphic sequences of 59 genes mainly involved in DNA repair and in cellular cycle. We found significant statistical associations with APE1, ERCC5-XPG, LIG1, CDKN2A, CCND1, XRCC2, BARD1 and RAD52.
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In this study we demonstrated that some polymorphic sequences of APE1, ERCC5-XPG, CCND1, BARD1 and RAD52 are associated with decreased risk for cancer of upper aero-digestive tract, whereas polymorphic sequences of XRCC2, CDKN2A and LIG1 are associated with increased cancer risk.
