Head and neck cancer was closely related with habitual use of cigarette and alcohol. Those cancer patients are susceptible to develop multiple primary tumors (MPTs). In this study, we utilized the single nucleotide polymorphisms (SNPs) array (Affymetrix Axion Genome-Wide TWB 2.0 Array Plate) to investigate patients’ risks of developing multiple primary cancers. We recruited 712 male head and neck cancer patients between Mar 1996 and Feb 2017. Two hundred and eighty-six patients (40.2%) had MPTs and 426 (59.8%) had single cancer. Four hundred and twelve normal controls were also recruited. A list of seventeen factors was extracted and ten factors were demonstrated to increase the risks of multiple primary cancers (alcohol drinking, rs118169127, rs149089400, rs76367287, rs61401220, rs141057871, rs7129229, older age, rs3760265, rs9554264; all were p value < 0.05). Polygenic scoring model was built and the area under curve to predict the risk developing MPTs is 0.906. Alcohol drinking, among the seventeen factors, was the most important risk factor to develop MPT in upper aerodigestive tract (OR: 7.071, 95% C.I.: 2.134–23.434). For those with high score in polygenic model, routine screening of upper digestive tract including laryngoscope and esophagoscope is suggested to detect new primaries early.
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