The hypothesis has been proposed that women may be more susceptible than men to smoking-caused lung cancer. However, the results of studies that have compared the association between smoking and lung cancer in men and women using appropriate comparisons do not support this hypothesis.
The results of the Multi-Ethnic Cohort Study indicated that for a given degree of cigarette smoking, African Americans had a higher risk of lung cancer compared with other racial/ethnic groups. Menthol cigarettes have been hypothesized as one potential factor contributing to the observed greater susceptibility to smoking-caused lung cancer in African Americans, but menthol cigarettes have not been observed to be associated with a higher risk of lung cancer than nonmenthol cigarettes.[7,8]
Cigarette smoking is the primary risk factor
The epidemic of lung cancer in the 20th century was primarily due to increases in cigarette smoking, the predominant cause of lung cancer. The threefold variation in lung cancer mortality rates across the United States more or less parallels long-standing state-specific differences in the prevalence of cigarette smoking. For example, average annual age-adjusted lung cancer death rates for 1996 to 2000 were highest in Kentucky (78 deaths per 100,000 individuals) where 31% were current smokers in 2001; whereas the lung cancer death rates were lowest in Utah (26 deaths per 100,000 individuals), which had the lowest prevalence of cigarette smoking (13%).
The biology of carcinogenesis
Understanding the biology of carcinogenesis is crucial to the development of effective prevention and treatment strategies. Two important concepts in this regard are the multistep nature of carcinogenesis and the diffuse field-wide carcinogenic process. Epithelial cancers in the lung appear to develop in a series of steps extending over years. Epithelial carcinogenesis is conceptually divided into three phases: initiation, promotion, and progression. This process has been inferred from human studies identifying clinical-histological premalignant lesions (e.g., metaplasia and dysplasia). The concept of field carcinogenesis is that multiple independent neoplastic lesions occurring within the lung can result from repeated exposure to carcinogens, primarily tobacco. Patients developing cancers of the aerodigestive tract secondary to cigarette smoke also are likely to have multiple premalignant lesions of independent origin within the carcinogen-exposed field. The concepts of multistep and field carcinogenesis provide a model for prevention studies.
Factors associated with increased risk of lung cancer
The most important risk factor for lung cancer (and for many other cancers) is cigarette smoking.[11,12,13] Epidemiologic data have established that cigarette smoking is the predominant cause of lung cancer. This causative link has been widely recognized since the 1960s, when national reports in Great Britain and the United States brought the cancer risk of smoking prominently to the public's attention. The percentages of lung cancers estimated to be caused by tobacco smoking in males and females are 90% and 78%, respectively. The manufactured cigarette has changed over time, but there is no evidence to suggest that changes such as "low tar" or "low nicotine" cigarettes have resulted in reduced lung cancer risks. Cigarette smoking is the most important contributor to the lung cancer burden because of its high prevalence of use and because cigarette smokers tend to smoke frequently, but cigar and pipe smoking have also been associated independently in case-control and cohort studies with increased lung cancer risk.[14,15] The cigar risks are of particular concern because of the increased prevalence of cigar use in the United States.