Date: Tuesday Aug. 16, 2011 6:47 PM ET

TORONTO — Cigarette smoking has long been linked to bladder cancer, but the risk of the disease developing appears to have climbed higher over the last several decades, especially among women who regularly light up, a large U.S. study has determined.

the study by the U.S. National Cancer Institute, which tracked almost 500,000 people over 11 years, found the likelihood of a smoker getting bladder cancer is about four times higher than someone who has never smoked.

Furthermore, the risk for female smokers now equals that for male tobacco users, according to the study published in this week’s edition of the Journal of the American Medical Association.

“So in our study, 50 per cent of bladder cancer in men and 50 per cent of bladder cancer in women was explained by smoking,” said Neal Freedman, an NIH investigator who led the research.

Earlier epidemiological research, some of it going back to the 1960s and ’70s, had estimated the “population attributable risk” at 50 to 60 per cent for male smokers and 20 to 30 per cent for their female counterparts, Freedman said Tuesday from Rockville, Md.

“But previous studies generally occurred in populations where women smoked less than men,” he said. “And so (now) in the U.S. population and most of the western world — I’m not certain about Canada, but I believe also — men and women smoke relatively similar amounts.”

To conduct the research, Freedman and colleagues used data from the National Institutes of Health-AARP Diet and Health Study, in which almost 500,000 men and women completed a lifestyle questionnaire and were followed up between October 1995 and December 2006.

During that period, 3,896 men and 627 women were newly diagnosed with bladder cancer. the researchers found that former smokers were twice as likely as people who never used tobacco to develop bladder cancer. Those who had been smoke-free for at least 10 years had a lower incidence than those who quit for shorter periods or who still smoked.

“I think our work emphasizes the importance of preventing smoking initiation, and among people that smoke, quitting smoking,” said Freedman. “And that will have a really important effect on preventing bladder cancer.”

interestingly, the incidence of bladder cancer has remained relatively stable over the last 30 years, at the same time that overall smoking rates in Canada and the U.S. have declined.

in Canada, 7,200 cases of bladder cancer are expected to be diagnosed this year — 5,400 men and 1,800 women. About 1,850 people will die from the disease, Canadian Cancer Society estimates predict.

“The higher risk, as compared to studies reported in the mid- to late-1990s, may explain why bladder cancer rates haven’t declined,” said Freedman, noting that there may be other factors at work that complicate the picture.

Cigarettes and the smoke they produce have changed over the last 50 years, both in content and preparation, he pointed out. While amounts of tar and nicotine have been reduced, there have been apparent increases in concentrations of certain carcinogens, including beta-naphthylamine, a known bladder cancer-causing agent.

“In addition to that carcinogen there are many more, and all or some may play a role in bladder cancer.”

Dr. Michael Jewett, a uro-oncologist at Princess Margaret Hospital in Toronto, said the study’s risk estimates for U.S. smokers would likely hold true for Canadians as well.

“And I guess as we see more women smoking, we would expect there to be less difference between the genders,” said Jewett, who was not involved in the study.

While it’s not known what causes bladder cancer in people who have never smoked or been exposed to excess tobacco smoke, the link with the cancer-causing agents found in tobacco and industrial production have long been known.

“The urinary tract is a bit like the sewer systems: the bad things that go in come out,” said Jewett. “And the bladder itself, it’s the reservoir, so it will store until it’s convenient to be emptied, and things like the carcinogens in cigarette smoke … appear then to act on the lining of the bladder for longer than anywhere else.

“So it’s been well-established that there are carcinogens in the urine and cigarette smoking is probably the most well-known association.”

Bladder cancer affects about three or four times as many men as women and the average age of diagnosis is the late 60s, he said.

Typically, a patient’s first sign of bladder cancer is blood in the urine that’s visible to the naked eye. A sudden change in the frequency and-or urgency of urination is also a red flag, although other conditions such as kidney stones can cause similar symptoms.

“They need to be aware that if they see blood or if they have a change in the way their bladder is working, particularly if they’ve been a smoker or are a smoker or are around a smoker, they should have a visit to their doctor,” Jewett said.

it was seeing a gush of red urine that sent David Guttman of Georgetown, Ont., to the hospital and ultimately to a diagnosis of bladder cancer 17 years ago.

“It was as red as if someone had punctured a vein,” he said, explaining that blood in the urine is usually intermittent and may not appear again for another month, so people with the disease are often misdiagnosed initially.

Guttman, 71, had grown up with parents who smoked heavily, but after taking up the habit himself, he butted out for good 30 years before his diagnosis.

he was treated with a widely used drug to knock back the cancer, but like 80 per cent of patients with a malignancy in the lining of the bladder, the tumours kept recurring. five years ago, he had his bladder removed and now uses a urostomy bag.

Bladder cancer is the sixth most common malignancy among Canadians and the most expensive cancer to treat because of its recurring nature.

“When I was diagnosed, there was no one around to talk to,”said Guttman, who co-founded Bladder Cancer Canada to support patients, provide public education about the disease and to advocate for research funding.

the charitable organization is holding a series of five-kilometre bladder cancer awareness walks in various sites across Canada on Sept. 24.

“One of the problems that bladder cancer survivors and researchers and the system around it has with this disease is we haven’t had any real breakthroughs — new inventions, a new drug,” said Jewett. “And so as a result, the survivors are not in the spotlight.”