Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk

1

Introduction

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm among the head and neck tumors [1] and corresponds to 90% of oral cancer cases [1] . The tumor arises from lining mucosa of the oral cavity, mainly on the tongue and the floor of the mouth, and can impair functions of speech, swallowing, and chewing [22] . Worldwide, more than 377.000 new cases of the disease are diagnosed and more than 177,000 deaths are registered annually [10] . Because the high rates of incidence, morbidity, and mortality, OSCC has been became a serious public health problem over the years [4] . According to INCA (National Cancer Institute, Brazil), 15.190 new cases were estimated for the triennium 2020–22 in Brazil, while in the year of 2019 a total of 6605 OSCC Brazilian patients died due to this cancer [20] . The disease is highly prevalent among men around the age of 60 years old [6] , of which two-thirds are diagnosed with the tumor in advanced stages [1] and 50% of cases already present locally or regional metastasis [16] , factors that contribute for worst prognoses [19] .

Tumor development is strongly associated with tobacco use and alcohol consumption, and the interaction of both substances increases the OSCC risk [7] . However, the disease has been considered a complex multi-step process, in which genetic alterations play a key role for oral cavity carcinogenesis [113] . Among these alterations, the copy number variation (CNV) of genes related to the metabolism have pointed out by scientists including the CNV of GSTM1 and GSTT1 . These genes codify enzymes from the Glutathione S-Transferase (GST) family that performs phase II of biotransformation process and the enzymes GSTM1 and GSTT1 catalyze inactivation of cigarette smoking carcinogenic compounds [1214] .

Concerning the variety of these genes, zero copies represent the total genes deletion with the respectively lack of enzymatic activity [12] , effect that is associated with the susceptibility of many diseases including OSCC [8] . Nevertheless, the individual contribution of one and more copies of GSTM1 and GSTT1 to detoxification process is unknown. The description of a new technique has allowed the determination of each copy of these genes [5] , which was carried out in few investigations. It was reported that one copy of GSTT1 increased the endometrial cancer risk [15] , while the prostate cancer susceptibility was elevated by one copy of GSTM1 and by two or more copies of GSTT1 [9] . To the best our knowledge, there are no studies about the copy number of these genes and OSCC susceptibility in literature. Therefore, the aims of this study were to determine the CNV of GSTM1 and GSTT1 and investigate their possible association with the oral squamous cell carcinoma risk.