Smoking Linked to Increased Risk for Second Cancers

Alexander M. Castellino, PhD

November 10, 2014

Cigarette smoking is a well-established risk factor for primary cancers such as those of the lung, bladder, kidney, and head and neck.

Now, a federally funded study shows that the increased risk extends to the development of smoking-related second cancers and for mortality. The study was published online November 10 in the Journal of Clinical Oncology.

A pooled analysis of five large cohorts revealed that the risk for a smoking-related second cancer was 3.3 to 5.3 times higher in survivors who smoked 20 cigarettes or more per day before their first cancer diagnosis than in never smokers. The results were statistically significant.

This is the largest study to report on cigarette smoking and the heightened risk for smoking-related secondary cancers, lead study author Meredith S. Shiels, PhD, MHS, a research fellow in the division of cancer epidemiology and genetics at the National Cancer Institute, told Medscape Medical News.

As survival improves for a number of smoking-related cancers, patients are living longer; however, smoking increases the risk of developing a second smoking-related cancer among these survivors, Dr Shiels added.

This well-designed evaluation of the effects of smoking in cancer patients shows that current smokers are at significantly higher risk of developing second primary cancers, and are at significantly increased risk for death, Graham Warren, MD, PhD, chair of the American Society of Clinical Oncology (ASCO) tobacco cessation subcommittee, told Medscape Medical News.

The Pooled Analysis

Researchers pooled data from five large prospective epidemiologic cohorts that comprised more than 15,000 patients — 2552 patients with stage I lung cancer, 6386 with bladder cancer, 3179 with kidney cancer, and 2967 with head and neck cancer.

The team assessed the association between smoking status before the primary cancer diagnosis and second smoking-associated cancer risk.

Pooling the data was important for this analysis because large numbers of cancer survivors are required to assess second cancer risk, explained Dr Shiels. Individually, even the largest of cohorts would not have the power to address this question, she said.

Among survivors, 866 (6%) second smoking-associated cancers were diagnosed. These are distinct primary cancers, not metastases of the first cancers, Dr Shiels said.

For all four cancer types, survivors who smoked 20 or more cigarettes per day before their first primary diagnoses were more likely to develop a second smoking-associated cancer than those who never smoked, the researchers report.

For a person with stage I lung cancer, the risk for a second smoking-related cancer was 2.6 times higher in survivors who smoked fewer than 20 cigarettes per day than in never smokers, and was 3.3 times higher in survivors who smoked 20 cigarettes or more per day. Similar patterns were observed for survivors of kidney, head and neck, and bladder cancers.

Risk for death followed similar dose-related trends. For example, risk for death was 2.4 times higher in survivors of stage I lung cancer who smoked fewer than 20 cigarettes per day than in those who never smoked, and was 3.1 times higher in survivors who smoked 20 cigarettes or more per day.

Stressing the Importance of Smoking Cessation

Tobacco use is a rapidly growing healthcare problem. It is responsible for 30% of all cancer deaths and the increased risk for at least 17 types of cancers. It is also a strong modifiable risk factor for several malignancies.

"Our study demonstrates that healthcare providers should emphasize the importance of smoking cessation to all their patients, including cancer survivors," Dr Shiels said.

The study lends support to the 2014 Surgeon General's report on the association between tobacco smoking and risk for second primary malignancies.

Dr Warren provided an ASCO perspective on smoking and cancer. "As doctors, we want to give our patients the best chance possible at long-term survival. This study is a reminder for us to aggressively support and encourage tobacco cessation at every step of the way, and should be a wake-up call for all smokers to take the necessary steps to quit even after a cancer diagnosis," he said.

Cancer patients might not realize that they are at a higher risk for treatment complications, second primary cancers, and death if they continue to smoke. Although more research is needed on smoking and second cancer risks, healthcare providers should emphasize the importance of smoking cessation to cancer patients, Dr Shiels and colleagues write.

Dr Warren noted that "ASCO has committed to educating clinical oncologists and providing resources to help cancer patients quit using tobacco through annual meeting sessions, online educational resources, policy statements, and performance initiatives for practicing oncologists. However, these recommendations and guidelines must be put into practice for patients to realize a clinical benefit." The Tobacco Cessation Guide for Oncology Providers is available on the ASCO website.

Unfortunately, studies demonstrate that tobacco cessation is not routinely incorporated into clinical practice or research. This is desperately needed to help improve clinical outcomes for our cancer patients, Dr Warren told Medscape Medical News.

"We hope that these data will encourage other large cohorts to collaborate so that future studies can be powered to address important questions about risk factors for second cancers, said Dr Shiels.

This research was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The authors and Dr Warren have no financial disclosures.

J Clin Oncol. Published online November 10, 2014. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.