O7.9 Lung cancer

Lung cancer is a serious health problem in Australia (Cancer Council Australia 2004). In 2007, in Australia, lung cancer was the fourth most commonly diagnosed cancer in both males and females (excluding basal and squamous cell carcinoma of the skin), with a total of 9,703 diagnosed (AIHW & Cancer Australia 2011).Lung cancer is the leading cause of cancer deaths for both sexes. The occurrence of lung cancer was strongly related to age, with 84% of new lung cancers in males and 80% in females diagnosed in those aged 60 and over. Smoking is the largest single cause of lung cancer, responsible for 90% of lung cancers in males and 65% of lung cancers in females in Australia. Between 1982 and 2007, the incidence rate of lung cancer decreased in males by 32%, but increased in females by 72%, reflecting historical differences in smoking behaviour.

The risk of lung cancer in people who have pre-existing lung disease has been studied using case-control studies, which found an increased risk of lung cancer in people with bronchitis and emphysema, even after correcting for the smoking history. A cohort study of 2,507 patients with COPD followed for 60 months found an incidence of lung cancer of 16.7 per 1000 patient years.  The most frequent histological type was squamous cell (44%) followed by adenocarcinoma (38%) and small cell (12%).  A diagnosis of lung cancer was associated with less severe GOLD stage, older age, lower BMI and diffusing capacity of lung for carbon monoxide (DLCO) test <80% predicted (de Torres 2011).

A much larger cohort study performed record linkage of Danish national hospital and cancer registries. The investigators identified 236,494 patients admitted for COPD between 1980 and 2008, who were followed for median of 3.5 years. During the first year of followup, the Standardised Incidence Ratio (SIR) for any cancer was 3.1 (95%CI 3.0-3.2), and lung cancer 8.5 (95%CI 8.2-8.8). The cumulative risks for lung cancer in this COPD cohort after 1, 5 and 10 years were 1.8% (95% CI 1.7 to 1.9%), 3.6% (95% CI 3.6 to 3.7%) and 4.9% (4.9 to 5.0%) respectively (Kornum 2012) [evidence level III-2].

During the longitudinal follow-up of the COPDGene Study [an average follow-up of 5.7 years (+/-1.87 years)], a total of 169 subjects diagnosed with lung cancer were matched (for age, race, sex, smoking status, average smoking pack-years and years since quitting smoking) against 671 control subjects with no reported lung cancer diagnosis. Characteristics associated with a future risk of lung cancer included airflow obstruction as measured by FEV1/FVC, history of exacerbations in the previous year and the presence of visual emphysema. The results were similar when percentage predicted FEV1 was used as the measure of airflow obstruction (Carr 2018).

Research has suggested a mechanism for the association, through identification of single-nucleotide polymorphisms (SNPs) on chromosome 15 in the nicotinic acetylcholine receptor subunit genes (CHRNA3 and CHRNA5) that are associated with smoking behaviour and with an increased risk of lung cancer and COPD (Bierut 2010). The SNPs on chromosome 15 appear to have an independent effect on disease risk, as if you incorporate the smoking history into the statistical analyses, the genetic variants continue to contribute to lung cancer risk above and beyond the smoking behaviour (Bierut 2010).