Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.

Abstract

Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated.

Loss of Heterozygosity of Chromosome 3p21 Is Associated with Mutant TP53 and Better Patient Survival in Non–Small-Cell Lung Cancer

“…Although the initiation of these events may occur with exposure to tobacco smoke during adolescence, and these early tobacco exposures may lead to the creation of altered cellular fields in which clones containing 3p21 LOH are not present and are more susceptible to additional carcinogen damage (28,45,46). Extensions of loss in this region may require additional alterations to other tumor suppressor pathways as additional exposures continue to alter these cellular fields and select the malignant clones.…”

Upregulation of stem cell antigen-1 in the lung of neonatal mice exposed to environmental cigarette smoke

“…In the study in transplacentally exposed fetuses we burnt 2R1 cigarettes without filter, having a declared content of 44.6 mg tar and 2.5 mg nicotine each, which accounted for an average total particulate matter (TMP) in the exposure chambers of 83.2 mg/m 3 . In the study in neonatal mice and their dams we burnt 2R4F filtered cigarettes, having a declared content of 9.2 mg tar and 0.8 mg each, which accounted for an average TMP of 63.3 mg/m 3 . In both studies exposure was daily, 6 h/ day divided into two rounds with a 3-h interval.…”

“…In particular, early age smoking has been viewed as an independent risk factor for lung cancer, and adolescence may constitute a critical period during which tobacco carcinogens can induce fields of genetic alterations (3).…”

Rauchverbot ohne Kompromisse ist der einzige Weg aus der Misere

“…Die demographischen Daten der österreichischen Raucherpopulation lassen leider annehmen, dass derartige, neue Erkrankungsformen gerade hierzulande zu Tage treten werden. Bereits jetzt ist bei Rauchern die in jungen Jahren bereits mehr pack-years angesammelt hatten als die früheren Generationen, ein immer früheres Einsetzen von COPD, von entzündlichen Erkrankungen, von cardiovasculären Erkrankungen und von Malignomen zu verzeichnen [7,8]. Der weibliche Organismus scheint sowohl bei den rauchassoziierten entzündlich-degenerativen Erkrankungen, als auch bei der Malignominduktion durch Tabakprodukte noch wesentlich sensibler als der männli-che zu reagieren.…”

“…Wiewohl die zahlreichen, zum Teil gravierenden Auswirkungen von Passivrauch auf die intrauterine, die frühkindliche und kindliche Entwicklung seit vielen Jahren hinlänglich bekannt sind, kann noch niemand sagen, welche Auswirkungen der frühe, aktive Tabakkonsum auf den noch im Wachsen befindlichen Organismus hat [2,[4][5][6]. Umweltpathologen warnen heute vor "neuen" früh-degenerativen Erkrankungsformen und vor einem drastischen Anstieg von Malignomen im späteren Leben von Menschen, die früh quantitativ zu rauchen begonnen haben [7]. Die demographischen Daten der österreichischen Raucherpopulation lassen leider annehmen, dass derartige, neue Erkrankungsformen gerade hierzulande zu Tage treten werden.…”