Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

Abstract

Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. Here we evaluate aspects of sexual behaviour in relation to the risk of OPC (2,641 cases and 6,585 controls), using genetic variants associated with age at first sex (AFS) and number of sexual partners (NSP) to perform Mendelian randomization (MR) analyses. While univariable MR showed a causal effect of both later AFS and increasing NSP on OPC, results attenuated in the multivariable models (AFS IVW OR 0.7, 95%CI 0.4, 1.2, p= 0.21; NSP IVW OR 0.9, 95%CI 0.5 1.7, p= 0.76). We also found evidence for correlated pleiotropy in the genetic instruments for sexual behaviour, emphasising the need for multivariable approaches when performing MR of complex behavioural traits and the triangulation of evidence.