Familial cancer aggregation and the risk of lung cancer

Abstract

CONTEXT: Around 90% of lung cancer worldwide is attributable to cigarette smoking, although less than 20% of cigarette smokers develop lung cancer. Other factors such as diet, chronic lung diseases, occupation and possibly environmental agents also contribute to this cancer. Genetic factors seem to play a role in lung cancer, but the precise characteristics influencing lung cancer susceptibility are not known, since genetic factors are easily obscured by the strong environmental determinants of lung cancer, particularly smoking. OBJECTIVE:To estimate the effect that cancer occurrence among first-degree relatives has on the risk of lung cancer. DESIGN:Hospital-based case-control study. SETTING:The metropolitan region of São Paulo, Brazil.PARTICIPANTS: 334 incident lung cancer cases and 578 controls matched by hospitals. MAIN MEASUREMENTS:By means of a structured questionnaire, cases and controls were interviewed about cancer occurrence in first-degree relatives, tobacco smoking, exposure to passive smoking, occupation, migration and socioeconomic status. Non-conditional logistic regression was used to calculate the risk of familial cancer aggregation, the effect of cancer in first-degree relatives and smoking in conjunction, and for controlling confounders. RESULTS:The adjusted odds ratio (OR) revealed a slight, but not statistically significant, excess risk of lung cancer for subjects with a history of lung cancer in relatives (OR 1.21; 95% confidence interval [CI] 0.50 -2.92). The same was found among those with a history of other tobacco-related cancers in relatives (OR 1.36; 95% CI 0.87 -2.14). A step gradient effect was observed regarding lung cancer risk, in accordance with increases in the number of pack-years of cigarette consumption. An interaction between familial cancer aggregation and tobacco smoking was detected. CONCLUSIONS:A mildly elevated risk of lung cancer among persons with a positive history of lung and other tobacco-related cancers was observed. The finding of an interaction between the variables of familial cancer aggregation and smoking suggests that familial cancer aggregation could be considered as a marker of susceptibility, increasing the risk of lung cancer among smokers. These results improve our knowledge of lung carcinogenesis and can guide future cancer genetic studies.

Systematic review of the relationship between family history and lung cancer risk

“…In all, 31 studies were identified that provided risks of lung cancer stratified by family history of the disease (Tokuhata and Lilienfeld, 1963a, b;Lynch et al, 1982;Ooi et al, 1986;Samet et al, 1986;Gao et al, 1987;Kramer et al, 1987;Sellers et al, 1987;Tsugane et al, 1987;Horwitz et al, 1988;Wu et al, 1988Wu et al, , 1996McDuffie et al, 1989;Wu-Williams et al, 1990;Liu et al, 1991;McDuffie, 1991;Osann, 1991;Shaw et al, 1991;Pavlakou et al, 1993;Schwartz et al, 1996Schwartz et al, , 1999Wang et al, 1996;Brownson et al, 1997;Kreuzer et al, 1998;Mayne et al, 1999;Bromen et al, 2000;Wunsch-Filho et al, 2002;Etzel et al, 2003;Wu et al, 2004;Jin et al, 2005;Matakidou et al, 2005). Three studies (Lynch et al, 1982;Sellers et al, 1987;Schwartz et al, 1999) were excluded from the review as the same data were duplicated in subsequent studies.…”

Modern cancer epidemiological research: genetic polymorphisms and environment

“…39 From the pioneering study of Tokuhata & Lilienfeld 32 on familial aggregation of lung cancer, several studies have consistently demonstrated an increased prevalence of cancer among relatives of lung cancer patients. Table 1 shows data on smoking from a case-control study 40 and as can be noted, cigarette smoking has distinct effects on those with or without reported cancer cases in first-degree relatives. A joint effect was detected 40 with permission **Parents and siblings ***Odds ratio adjusted for gender, age and socio-economic status (four levels) ****95% confidence interval between the variables smoking and cancer in relatives on the risk of lung cancer.…”

“…Table 1 shows data on smoking from a case-control study 40 and as can be noted, cigarette smoking has distinct effects on those with or without reported cancer cases in first-degree relatives. A joint effect was detected 40 with permission **Parents and siblings ***Odds ratio adjusted for gender, age and socio-economic status (four levels) ****95% confidence interval between the variables smoking and cancer in relatives on the risk of lung cancer.…”

Another brick in the wall

“…The identification of at-risk populations will allow resources to be concentrated on early detection, with an improvement in outcomes. The well-structured article by Wünch-Filho et al 5 in this issue adds new evidence to the concept of genetic risk factors for lung cancer. …”