In 2012, investigators led by pathologist Mark Ladanyi, M.D., at Memorial Sloan Kettering Cancer Center studied genotyped 3,026 lung adenocarcinomas for the major EGFR mutations (exon 19 deletions and L858R) and KRAS (G12, G13) examining correlations with demographic, clinical, and smoking history data.
The researchers focused on KRAS, which is frequently mutated in lung adenocarcinomas, and found that smokers and people who never smoked (“never smokers”) had different KRAS mutations in their tumors. Smokers usually had a mutation called KRAS G12C, while never smokers typically had a mutation called KRAS G12D. Women were more likely than men to have the KRAS G12C mutation, and they developed the disease at a younger age and with a shorter history of smoking.
Dr. Ladanyi said the data support the theory that women are more vulnerable than men to carcinogenic effects of tobacco smoke. He commented that researchers have speculated for decades that women who smoke are at greater risk for lung cancer than men, but various analyses have produced conflicting data.
And back in 2003, Shinichi Toyooka, M.D., and colleagues at Kagawa Prefectural Central Hospital, Takamatsu, Japan, presented findings of an analysis of 1,775 lung cancer cases for mutations of the TP53 suppressor gene. The investigators looked for mutations characterized by an excess of G:C to T:A transversions thought to be characteristic of smoking-related cancers.
The transversions were present in 26% of male smokers who developed any type of lung cancer, compared with 37% of female smokers who developed lung cancer. Also, such transversions were found in 31% of males who developed lung cancer despite a history of never smoking, compared with 12% of such females, the study showed.
Dr. Toyooka said the study shows for the first time that cancers in female smokers have significantly more tobacco-related mutations, helping to explain the greater susceptibility of women to tobacco carcinogens.