LWBK1006-03 LWW-Govindan-Review November 24, 2011 11:19
Chapter 3•Etiology of Cancer Part 1 43ANSWERS
Answer 3.1. The answer is C.
Smoking increases the risk of developing all histologic types of lung can-
cer, including adenocarcinoma, squamous cell carcinoma, large cell carci-
noma, and small cell carcinoma. The strongest determinant of lung cancer
in smokers is duration of smoking. The risk also increases with the num-
ber of cigarettes smoked. Cessation of smoking avoids the further increase
in risk of lung cancer caused by continued smoking. However, the risk
of developing lung cancer in ex-smokers remains elevated for years after
cessation, compared to that of never smokers.Answer 3.2. The answer is D.
Cigarette smoke consists of many carcinogens. Data from carcinogenic-
ity studies, product analyses, and biochemical and molecular biological
investigations support a significant role for certain carcinogens in specific
types of tobacco-induced cancers. In this regard, evidence suggests a sig-
nificant role for polycyclic aromatic hydrocarbons andN-nitrosamines as
causative factors in lung cancer. Evidence also supports the role of aro-
matic amines as a cause of bladder cancer and a role forN-nitrosamines
as a cause for esophageal cancer. Nicotine itself is not known to initi-
ate cancer formation, but recent evidence suggests that nicotine through
nicotinic receptors may promote cellular proliferation.Answer 3.3. The answer is A.
Many cigarette smoke carcinogens are not active and require metabolic
activation to transform them into active carcinogens. Cytochrome P450
enzymes convert these compounds into electrophilic entities that can cova-
lently bind to DNA-forming DNA adducts. P-450 enzymes 1A1 and 1A2
are particularly important in the metabolic activation of some of the car-
cinogens in cigarette smoke. Other P450 enzymes involved in this process
include 1B1, 2A13, 2E1, and 3A4. 1A1 and 1B2 are induced by com-
pounds in cigarette smoke, and the induction of these enzymes may be
a critical aspect of cancer susceptibility in smokers. The cigarette smoke
carcinogens can undergo detoxification by glutathione-S-transferases and
uridine diphosphate -glucuronosyl transferases. Therefore, cancer suscep-
tibility may be determined by the balance achieved between activation of
the carcinogens in cigarette smoke and their detoxification. In addition,
polymorphisms in genes encoding these enzymes may influence an indi-
vidual’s risk of cancer from these carcinogens. Cellular repair systems can
remove the DNA adducts formed by smoke carcinogens and repair the
DNA, but they are not involved in metabolic activation of carcinogens in
cigarette smoke. Nucleotide excision repair enzymes are a component of
these repair systems.