Rheumatoid arthritis and cancer risk in the Million Women Study
TienYu Owen Yang, Sarah Floud, Gillian Reeves, Million Women Study Collaborators, Simon Abbott, Rupert Alison, S. Atkinson, Krys Baker, Angela Balkwill, Isobel Barnes, Judith L. Black, R G Blanks, Anna Brown, Andrew Chadwick, Dave Ewart, Sarah Floud, Kezia Gaitskell, Toral Gathani, Laura Gerrard, Adrian Goodill, C Hermon, Sau Wan Kan, Nicky Langston, Keren Papier, Kirstin Pirie, Gillian Reeves, K. M. Shaw, Emma Sherman, Karl Smith-Byrne, Helena Strange, Siân Sweetland, Ruth C. Travis, Lyndsey Trickett, Clare J. Wotton, O. Young, Emily Banks, Lucy Carpenter, Carol Dezateux, Sarah Floud, Julietta Patnick, Richárd Pető, Gillian Reeves, Cathie Sudlow
Abstract
BACKGROUND: Most previous studies of rheumatoid arthritis (RA) and cancer risk have lacked information on potential confounding factors. We investigated RA-associated cancer risks in a large cohort of women in the UK, taking account of shared risk factors. METHODS: In 1996-2001, women aged 50-64, who were invited for routine breast screening at 66 National Health Service (NHS) screening centres in England and Scotland, were also invited to take part in the Million Women Study. Participants provided information on sociodemographic, lifestyle and health-related factors, including RA, and were followed up for cancers and deaths. Cox regression yielded RA-associated hazard ratios (HRs) of 20 cancers, adjusted for 10 characteristics including smoking status and adiposity. RESULTS: Around 1.3 million women (half of those invited) were recruited into the study. In minimally adjusted analyses, RA was associated with the risk of 13 of the 20 cancers. After additional adjustment for lifestyle factors, many of these associations were attenuated but there remained robust evidence of RA-associated increases in the risk of lung (HR 1.21, 95% confidence interval 1.15-1.26), lymphoid (1.25, 1.18-1.33), myeloid (1.12, 1.01-1.25), cervical (1.39, 1.11-1.75) and oropharyngeal (1.40, 1.21-1.61) cancers, and decreases in the risk of endometrial (0.84, 0.77-0.91) and colorectal (0.82, 0.77-0.87) cancers. CONCLUSIONS: After taking account of shared risk factors, RA is positively associated with lung and certain blood and infection-related cancers, and inversely associated with colorectal cancer. These findings are consistent with existing hypotheses around immune response, susceptibility to infections, and chronic inflammation. The inverse association observed for endometrial cancer merits further investigation.