Table 1 Mutational signatures and cancer types associated with tobacco smoking.

Information about the age-adjusted odds ratios for current male smokers to develop cancer is taken from (24). Odds ratios for small cell lung cancer, squamous cell lung cancer, and lung adenocarcinoma are for an average daily dose of more than 30 cigarettes. Odds ratios for cervical and ovarian cancers are for current female smokers. Detailed information about all mutation types, all mutational signatures, and DNA methylation is provided in table S2. Nomenclature for signature identification numbers is consistent with the COSMIC database ( The numbers of smokers and nonsmokers are unknown (i.e., not reported in the original studies) for acute myeloid leukemia, stomach, ovarian, and colorectal cancers. The patterns of all mutational signatures with elevated mutation burden in smokers are displayed in Fig. 2B. N/A denotes lack of smoking annotation for a given cancer type. Asterisks indicate that a signature correlates with pack years smoked in a cancer type. N.S. reflects cancer types without statistically significant elevation of mutational signatures. The odds ratio for all cancer types is not provided.

Cancer typeOdds
NonsmokersSmokersTotal number of
mutational signatures
found in the cancer type
Signature 4
found in
cancer type
Mutational signatures
with elevated
mutation burden
in smokers
versus nonsmokers
(q < 0.05)
All cancer typesND 1062249026Y4, 5*
Small cell lung cancer111.331456YN.S.
Lung squamous103.571688Y4*, 5
Lung adenocarcinoma21.91205587Y2*, 4*, 5*, 13*
Larynx13.261175Y4*, 5
Oral cavity4.2982655Y5*
Esophagus squamous3.9991939Y5
Esophagus adenocarcinoma3.9671759Y N.S.
Liver2.915723519Y4*, 5, 16
Acute myeloid leukemia2.02022NN/A