The phenomenon of more frequent metastases from primary tumors in smokers, or of more rapid progression of primary or metastatic tumor tissue in them, was referenced by Murin and Inciardi in patients with myelogenous leukemia, prostate cancer, and malignant melanoma. This phenomenon is not restricted to these tumor types, having also been documented in patients with carcinomas of the endometrium,5–
as well as those with breast cancer. Most metastases from these tumors are nonpulmonary, indicating the presence of smoking-related systemic factors, which either directly stimulate malignant cells or inhibit host antitumor defense mechanisms, resulting in accelerated growth, invasion, or metastasis by these cells. The probability of smoking-induced inhibition of host antitumor immune defenses was recognized by Murin and Inciardi and is supported by evidence documenting widespread impairment of immune responses in smokers,10–
including the easily measured responses to vaccines against influenza11–
and hepatitis B.12
Most tumor types with smoking-associated worse prognosis are not hormone sensitive, suggesting that smoking-induced endocrine abnormalities cannot explain this general pattern. The possibility of increased pulmonary metastases having resulted from direct influence on pulmonary tissue by tobacco smoke seems remote.