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

BACKGROUND: 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. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results 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). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

Physical activity during pregnancy in a prospective cohort of British women: results from the Avon longitudinal study of parents and children.

We sought to examine the levels, types, and changes of physical activity and their correlates among pregnant women. Data came from 9,889 pregnant women with due dates between April 1, 1991 and December 31, 1992 who were participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) in Bristol, Avon, Southwest England. Self-reported physical activity during pregnancy was collected via questionnaires administered at 18 and 32 weeks of gestation. We found, at 18 weeks of gestation, the prevalence of engaging in physical activity that was sufficient to cause sweating for ≥ 3 h/week (referred to as strenuous physical activity) was 48.8%. This percentage was similar at 32 weeks of gestation. The most common physical activity during pregnancy reported by these women was brisk walking, followed by swimming and ante-natal exercise. In models that mutually adjusted for all characteristics examined, younger women, women in lower social classes, those not employed during pregnancy, married and parous women (compared to those not in each of these groups) were more likely to report engaging in strenuous physical activity. After becoming pregnant, about two out of three of these women reported reducing physical activity levels at 18 weeks of gestation. In mutually adjusted models, women who were younger, fit and well, parous, and women from lower social classes (compared to those not in each of these groups) were less likely to report reducing their physical activity. Our findings provide insights that are relevant to the design of future observational and intervention studies concerned with the effects of physical activity during pregnancy on health outcomes for mothers and offspring.

What influences diet in early old age? Prospective and cross-sectional analyses of the Boyd Orr cohort.

BACKGROUND: The aim of this study is to identify the socio-economic and health-related factors in childhood and later life associated with healthy eating in early old age. METHODS: The study is based on surviving members of the Boyd Orr cohort aged 61-80 years. Data are available on household diet and socio-economic position in childhood and on health and social circumstances in later life. A 12-item Healthy Diet Score (HDS) for each subject was constructed from food frequency questionnaire responses. Complete data on all exposures examined were available for 1234 cohort members. RESULTS: Over 50% of study members had inadequacies in at least half of the 12 markers of diet quality. In multivariable models having a childhood diet which was rich in vegetables was associated with a healthy diet in early old age. The HDS for those in the upper quartile of childhood vegetable intake was 0.30 (95% confidence interval -0.01 to 0.61) higher than those with the lowest intake levels (P-trend across quartiles = 0.04). The adult factors that were most strongly associated with a healthy diet were not smoking, being an owner-occupier, and taking anti-hypertensive medication. CONCLUSION: Our analysis indicates that diet in early old age is influenced by childhood vegetable consumption, current socio-economic position, and smoking. Interventions for improving the diet of older people could usefully focus on both encouragement of healthy diet choices from an early age and higher levels of income or nutritional support for older people.