The subjects were recruited from an ongoing SCCHN study as described previously . 33Briefly, the cases were patients with newly diagnosed, untreated SCCHN that were histologically confirmed at The University of Texas M D Anderson Cancer Center between October 1999 and October 2007. Patients with second SCCHN primary tumors, primary tumors of the nasopharynx or sinonasal tract, primary tumors outside the upper aerodigestive tract, cervical metastases of unknown origin, or any histopathological diagnosis other than SCCHN were excluded. Of the eligible cases, the response rate was approximately 93% and only few minority subjects were recruited. As a result, the analysis included 1109 non-Hispanic white subjects with primary tumors of the oral cavity (n = 326; 29.4%),oropharynx (n = 566; 51.0%), or larynx / hypo-pharynx (n = 217; 19.6%). Among the eligible control subjects with a response rate of 85%, 1130 cancer-free controls were recruited from hospital visitors accompanying the patients to the clinics but not seeking medical care, who were genetically unrelated to the enrolled case subjects or each other. We first surveyed potential control subjects at the clinics by using a short questionnaire to determine their willingness to participate in research studies and to obtain demographic information for frequency matching to the cases by age (±5 years) and sex. Having obtained a written informed consent, we interviewed each eligible subject to collect additional information about risk factors, such as tobacco smoking and alcohol use and a one-time sample of 30 ml of blood for biomarker tests. The research protocol was approved by the M.D. Anderson Cancer Center institutional review board.