The Texans said McNair died peacefully, surrounded by family, including his wife, Janice.
McNair battled both leukemia and squamous cell carcinoma for nearly two decades before his death. McNair explained his fight against skin cancer was complicated by a chronic form of leukemia.
The fight included both radiation and chemotherapy, along with an experimental treatment with doctors at MD Anderson Cancer Center.
McNair had surgery in fall of 2013 to remove an abnormal growth behind his left ear. Doctors told him that they couldn't remove all the cancerous cells and that McNair had an aggressive form of the disease.
He then underwent six weeks of radiation, chemotherapy and CT scans by April 2014, and it later showed that the cancer cells were virtually gone.
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McNair is survived by his wife, sons, Cal and Cary, daughters, Ruth and Melissa, 15 grandchildren and two great grandsons, the team said.
Bob McNair, owner of Houston Texans, passes away at 81
Texans players and NFL react to Bob McNair's passing