Blot, 1984; Osann et al., 1993; Risch et al., 1993), although some have not (Doll and Peto, 1976; Halpern et al., 1993). While some might hypothesize that the difference in cancer risks between men and women are due to differing baseline nonsmoking rates (Prescott et al., 1998), this was found not to be the case using summary statistics from several large cohort studies (Risch et al., 1994). An increased risk in women is also evidenced by data showing that there is a higher risk for lung cancer in women at similar ages of initiation and the risks are the same for women who start smoking over age 25 as for men over age 20 (Hegmann et al., 1993). In a study of lung cancer risk among persons who switched from filtered to nonfiltered cigarettes, both women and men had a lower lung cancer risk if they smoked similar amounts of cigarettes per day before and after switching (Augustine et al., 1989). However, women had a greater likelihood of compensation and smoking more cigarettes, especially at lower doses. For similar levels of increased cigarettes per day, women had a much higher risk of lung cancer. There are several plausible explanations for this increased risk that bear directly on the effects of PREPs. The increased risk observed in women might be due to smoking behavior and/or biological differences. For example, women may be at higher risk because they have begun smoking in recent times with lower-tar and nicotine cigarettes (Thun et al., 1997), which can deliver greater amounts of TSNAs (Hoffman and Hoffman, 1997). There is a lack of evidence, however, showing consistent differences in greater smoking topography, but this may be because both men and women were smoking similar types of cigarettes.
Another explanation for a higher lung cancer risk in women might be related to biological differences between men and women. There might be a hormonal relationship, because women more commonly have estrogen or progesterone receptors in lung cancer (Kaiser et al., 1996). Two studies found a high abundance in both males and females, but a difference between the two could not be discerned (Canver et al., 1994; Su et al., 1996). Also, because women suffer more tobacco withdrawal symptoms during menses, they might have greater lifetime exposure (O’Hara et al., 1989). Women have higher levels of carcinogen-DNA adducts in lung tissues, even though they have the same or lower levels of smoking (Ryberg et al., 1994a), which supports the latter hypothesis. Separately, Chinese women have a higher risk of lung cancer if they have more and shorter menstrual cycles (Liao et al., 1996; Gao et al., 1987). The frequency of p53 mutations is higher in men, consistent with the greater amounts of smoking, but women more commonly have G→T transversions (Kure et al., 1996), suggesting a particular susceptibility to tobacco smoke carcinogens. Women might also be more susceptible if they have particular metabolic polymorphisms that affect carcinogen detoxification (Mollerup et