Smoking is responsible for a third of all cases of severe rheumatoid arthritis, according to a study of more than 2,000 people.
In people who are genetically predisposed towards the debilitating condition it accounts for more than a half of cases, the Swedish study found.
Rheumatoid arthritis is the painful swelling of the joints, thought to be caused by the body's own immune system attacking itself. It often begins to affect people between 40 and 60, and is three times more common in women than in men. About 400,000 people suffer from it in Britain.
Researchers at the Karolinska Institute in Stockholm asked 1,200 people with RA about their smoking habits, as well as almost 900 people without it. Both sets were matched for age, sex, and other factors.
They found people who had smoked heavily throughout their lives - at least 20 a day for at least 20 years - were more than two-and-a-half times as likely to test positive for a type of antibody, called the anticitrullinated protein/peptide antibody (ACPA), that is now closely associated with the most common and severe form of RA.
Based on this and other figures, they calculated that smoking accounted for 35 per cent of ACPA-positive cases of RA, and a fifth of cases of the disease overall.
Among people who were genetically susceptible to the disease, the researchers concluded that smoking was responsible for more than half (55 per cent) of ACPA-positive cases.
However, they found that in all but the heaviest smokers, the risk of developing RA diminished once a person stopped smoking.
The report is published today online in the British Medical Journal's Annals of the Rheumatic Diseases.
Jane Tadman, from Arthritis Research UK, commented: "We’ve also known for some time that lifestyle factors such as smoking, and also eating a lot of red meat and drinking large amounts of caffeine may also affect the risk of developing the disease.
"As there is little you can do about changing your genetic make-up, it seems sensible to reduce the other risk factors that you actually have some control over. So stopping smoking would be one obvious way of doing this."
By Stephen Adams, Medical Correspondent 6:30AM GMT 14 Dec 2010