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Cancer risks were elevated among patients with systemic lupus erythematosus (SLE) -- both women and men -- and the list of specific cancers that carry high risks was long.

A systematic review and meta-analysis found that the overall cancer risk was increased for SLE patients, with a pooled standardized incidence rate (SIR) of 1.28 (95% CI 1.16-1.42), according to Xiaoyun Xu, MD, and colleagues from Nanjing Medical University in China.

For women, the SIR was 1.49 (95% CI 1.15-1.93, P=0.012, I ² =72.7%), while for men it was 1.59 (95% CI 1.18-2.14, P=0.001, I ² =78.8%), the researchers reported in .

Despite considerable progress in diagnosis and treatment that has led to increased survival among SLE patients, their mortality risks remain two- to fivefold higher than the general population -- not only for all-cause mortality but also for cancer deaths, the team explained.

But the true incidence of cancer in SLE remains uncertain, because earlier studies have found conflicting and incomplete results.

Therefore, to more clearly determine the rates of various cancers in SLE patients, Xu and co-authors searched the literature for studies published through May 2018, identifying 24 eligible studies. Malignancies were classified as lymphatic and hematopoietic, reproductive, urinary, digestive, respiratory, and "other."

For the lymphatic/hematopoietic group, in 11 studies there was an increased risk of non-Hodgkin's lymphoma (SIR 4.93, 95% CI 3.81-6.36) and also for Hodgkin's lymphoma (SIR 2.60, 95% CI 2.14-3.17). Increases were also seen in 10 studies of leukemia (SIR 2.01, 95% CI 1.64-2.47) and in four studies of multiple myeloma (SIR 1.48, 95% CI 1.02-2.14).

In the reproductive cancer category, there were 19 studies of SLE and breast cancer. "Remarkably," the researchers commented, there was no association for breast cancer (SIR 0.89, 95% CI 0.77-1.04), nor was there an association for uterine cancer (SIR 0.70, 95% CI 0.46-1.07) or ovarian cancer (SIR 0.92, 95% CI 0.74-1.33).

Increased risks were seen, however, for cervical cancer (SIR 1.56, 95% CI 1.29-1.88) and cancer of the vagina/vulva (SIR 3.48, 95% CI 2.69-4.50).

For urinary cancers, there was a decreased risk for prostate cancer (SIR 0.78, 95% CI 0.70-0.88), but increased risks for renal cancer (SIR 2.10, 95% CI 1.11-3.96) and bladder cancer (SIR 1.86, 95% CI 1.16-2.99).

Among digestive tract cancers, significant associations were seen for esophageal (SIR 1.64, 95% CI 1.43-1.87), gastric (SIR 1.31, 95% CI 1.04-1.63), and hepatobiliary cancers (SIR 2.37, 95% CI 1.67-3.38), though not for pancreatic (SIR 1.24, 95% CI 0.97-1.60) or colorectal cancer (SIR 0.97, 95% CI 0.85-1.09).

For cancers of the respiratory tract, significant associations were observed between SLE and lung cancer (SIR 1.62, 95% CI 1.40-1.87), oropharyngeal cancer (SIR 1.52, 95% CI 1-2.30), and laryngeal cancer (SIR 2.90, 95% CI 1.82-4.62).

The "other cancers" group included cutaneous melanoma, which showed a decreased risk (SIR 0.72, 95% CI 0.56-0.93), while increased risks were found for nonmelanoma skin cancers (SIR 1.41, 95% CI 1.07-1.87) and thyroid cancer (SIR 1.80, 95% CI 1.46-2.23). No association was seen for brain cancer.

"Several potential mechanisms could account for cancer development in SLE patients. These patients, by virtue of their disease, have basic defects in immune cell function, resulting in immune dysregulation which might prevent aberrant cells from being removed and eventually contributing to increased cancer risk," the authors noted.

In addition, immunosuppressive drugs could contribute to the risk, as could smoking, genetic factors, and environmental triggers. There have also been reports of potential roles for co-stimulatory molecules such as CTLA4 and OX40L that may participate in the pathogenesis of SLE and that have been linked with carcinogenesis.

"Future high-quality research is required to verify our findings and this should pay more attention to the underlying mechanisms between SLE and cancer risks," they concluded.

A limitation of the study, the team said, was the incomplete information on potential confounding factors such as age, sex, ethnicity, and environmental triggers.

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