Tobacco and Public Health - TCSC Indonesia

(U.S. Dept. of Health Education and Welfare et al. 1979). The burning of tobacco
produces numerous genotoxic compounds, including polynuclear aromatic hydrocarbons,
heterocyclic amines, nitrosamines, and aromatic amines (IARC Working
Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans 1986;
Manabe et al. 1991; Alexandrov et al. 1996; Hoffmann and Hoffman 1997). The large
intestine is exposed to these compounds either through the circulatory (Yamasaki and
Ames 1977) or digestive system (Kune et al. 1992a). DNA adducts to metabolites of
benzo[a]pyrene, a carcinogenic polycyclic aromatic hydrocarbon, are detected more
frequently in the colonic mucosa of smokers compared to non-smokers (Alexandrov
et al. 1996). DNA adduct levels in the normal-appearing colonic epithelium of colorectal
cancer patients occur at a higher frequency than in non-cancer patients (Pfohl-
Leszkowicz et al. 1995). The apparently long induction period of at least 3 or 4 decades
between the presumably genotoxic event and ultimately diagnosis of malignancy is consistent
with the natural history of colorectal cancer (Giovannucci and Martínez 1996).
Unresolved issues and implications
EDWARD GIOVANNUCCI 453
The data just summarized strongly support an association between smoking and risk
of colorectal cancer. Dose–response relations have been reported for pack-years, smoking
duration, smoking intensity, smoking history in the distant past, and younger age
at initiation of smoking. Relative risk comparing the high versus low categories of
these factors have generally been in the range of 1.3–1.8. As most of these variables
tend to be correlated, teasing out which are the most relevant factors is difficult,
although clearly those who began early and smoked most intensely for many years are
at highest risk. To what degree and how quickly risk drops after one ceases smoking
remains somewhat in question, but most data suggest that part of the excess risk
persists indefinitely in past smokers (Wu et al. 1987; Giovannucci et al. 1994a, b;
Slattery et al. 1997; Stürmer et al. 2000). Only one study (Chao et al. 2000) found that
the excess risk appears to approach zero after about 20 years since quitting. While
smoking at any age has numerous health benefits, for colorectal cancer the avoidance
of smoking at early ages appears particularly important.
Generally, associations have been observed for both colon and rectal cancers,
although, in several studies (Doll and Peto 1976; Chute et al. 1991; Inoue et al. 1995;
Nyrén et al. 1996), an association was observed or suggestive only with rectal cancer.
However, in one of these studies (Chute et al. 1991), with additional follow-up
(Giovannucci et al. 1994a), an association emerged for colon cancer. In most studies
that have distinguished among colon and rectal cancer, the association has been
stronger for rectal cancer (Tverdal et al. 1993; Doll et al. 1994; Giovannucci et al. 1994a;
Heineman et al. 1994; Newcomb et al. 1995; Chyou 1996 #6191; Chao et al. 2000),
though present for both. Overall, whether differences exist between the proximal and
distal colon has not been adequately addressed.