Background Over 41,000 people are diagnosed with lung cancer annually in the UK with only 8% of men, and 9% of women surviving at least 5 years after diagnosis. Antibodies against the endothelial cell protein endoglin are proving promising in early clinical trials [1]. Many individuals with hereditary haemorrhagic telangiectasia (HHT) have inherited endoglin mutations. This autosomal dominant trait affects approximately 1 in 5,000 people, causing multi-systemic vascular lesions. We hypothesised that lung cancer rates may differ in individuals with HHT.

Methods To provide sufficient power to compare lung cancer rates in HHT patients and controls, we developed a questionnaire capturing data on multiple relatives per respondent, powered to detect differences in lung cancer rates. Blinded to cancer responses, reports of HHT-specific features allowed assignment of participants and relatives as HHT-subject, unknown, or control. Logistic and quadratic regression were used to calculate crude and age-adjusted odds ratios.

Results By data download on 30.6.2012, 1,307 participants (including 1,012 HHT-subjects, 142 controls) completed the questionnaire. Ages (medians 55/53ys), gender (65/65% female) and general demographics were similar. The number of current/former smokers did not differ significantly between HHT and control groups (p = 0.38), but the HHT arm reported significantly greater pack year smoking histories than the controls (Mann Whitney p = 0.01). Combining data of participants and relatives resulted in a control-arm of 2,817 (52% female), and HHT-arm of 2,166 (58% female). Median ages were77ys [IQR 65–82] and 66ys [IQR 53–77] respectively. Rates of 15 cancers predominantly recognised as primary cancers in the control group generally matched the age standardised frequency of the general population. The ratio of observed/expected incidence was significantly higher for cancers at common sites of metastatic spread (lung, liver and brain). As expected cancer rates increased with age (p < 0.0001, all cancers). In both crude and age-adjusted regression, lung cancers were significantly less frequent in the HHT arm compared to controls (age-adjusted odds ratio 0.48 [0.30, 0.70], p = 0.0012).

Conclusions Individuals with HHT may be protected against primary and/or metastatic lung cancer. This does not appear to be due to reduced smoking habit.

References

1. Bernabeu and Shovlin, Thomson Reuters Pharma (21 December 2011) [Online].