Tobacco and Public Health - TCSC Indonesia

482
TOBACCO AND PANCREAS CANCER
Histological and experimental studies
There is also strong evidence that smoking is associated with histologic alterations and
molecular damages of the pancreas.
In a large autopsy study based on 22 344 slides from 560 autopsied subjects, histological
alterations in the ductal epithelium was strongly associated with smoking habits.
Only 5.4% of the non-smokers had medium to high percentages of ductal cells with
atypical nuclei. This rose to 50.7% in light smokers and to 74.9% in smokers of more
than 40 cigarettes/day. Advanced findings (increased numbers) of cells with atypical
nuclei were found in the acinar cells of the parenchyma in only 1.8% of non-smokers;
11.4% in smokers of less than 20 cigarettes/day; 29.2% in smokers of 20–39
cigarettes/day and 69.1% in smokers of more than 40 cigarettes/day. Moderate or
advanced hyaline thickening of arterioles in 12.8% of the non-smokers increased to
74.4% in the heaviest smoking group. A similar relationship was observed for fibrous
thickening in the arteries (Auerbach and Garfinkel 1986).
The nicotine-derived nitrosamine, nitrosamine 4-(methylnitrosamino)-1-
(3-pyridyl)-1-butanone (NNK), is known to cause adenocarcinomas of the lung
and pancreas in laboratory animals (Hoffmann et al. 1993, Schuller et al. 1993),
and is thought to be largely responsible for the development of these cancers
in smokers. In particular, NNK has genotoxic effects on cells, such as the formation
of DNA adducts and mutations in the RAS gene. Experimental studies have
demonstrated that aromatic amines and nitroaromatic hydrocarbons are metabolized
by the pancreas and may be involved in the etiology of human pancreatic
cancer (Anderson et al. 1997), and that DNA damage derived from carcinogen exposure
is involved in pancreatic carcinogenesis and in particular that smoking was
positively correlated to the level of total DNA adducts in pancreatic cancer tissue
(Wang et al. 1998).
From these observations, it was hypothesized that polymorphisms in genes that
encode carcinogen-metabolizing enzymes could also affect the risk of smoking-related
pancreatic cancer. In particular, it has been shown that the glutathione S-transferase T1
(GSTT1) enzyme protects pancreatic cells from the damaging effects of tobacco smoking
and that lacking this enzyme may increase the risk of smoking-related pancreatic
cancer (Duell et al. 2002). Using biological material collected in a large case-control
study in the San Francisco Bay Area, it was shown that the XRCC1 (X-ray repair
cross-complementing group 1) 399Gln allele, which has been associated with elevated
biomarkers of DNA damage in human cells, is also a potentially important determinant
of susceptibility to smoking-induced pancreatic cancer (Duell et al. 2002). Still,
previous smaller studies did not find significant associations between GSTM1, GSTT1,
NAT1 or CYP1A1 polymorphisms and pancreatic cancer susceptibility (Bartsch et al.
1998; Liu et al. 2000).