Study Highlights Sex Differences in Lymphoma Incidence and Mortality

In many cancer types, male sex is associated with increased risk and lower survival compared with females. A recent study of the Swedish population explored this pattern in the context of lymphomas and found that men had a significantly higher incidence and a tendency for higher mortality in most lymphoma subtypes.

Lymphoma has more than 80 subtypes, and there is significant variation between subtypes for aggressiveness and treatability. These various subtypes also have shown notable male predominance, and male sex is listed as a risk factor in the International Prognostic Score for classic Hodgkin lymphoma (cHL) based on recent data.

“The underlying reasons for sex differences in lymphoma incidence remain unknown but have been suggested to reflect different exposures to environmental carcinogens and/or intrinsic disparities such as immunological and hormonal factors, body size, and tumor biology, in men and women,” the authors wrote.

The nationwide population-based study, published in American Journal of Hematology, used data from the Swedish Lymphoma Register to assess sex differences in lymphoma incidence and mortality from 2000 to 2019. The study results were also compared to Danish Lymphoma Register data.

A total of 36,795 cases of lymphoma affecting 36,553 patients were identified, with the most common subtypes being large B-cell lymphoma (LBCL; 30.5%), follicular lymphoma (FL; 13.8%), and cHL (8.9%). Male-to-female incidence rate ratios (IRRs) and excess mortality ratios (EMRs) adjusted for age and calendar year were predicted via Poisson regression.

Of the cases identified, 20,738 (56.4%) patients were men and 16,057 (43.6%) were women. The median ages at diagnosis were 68 and 70 years, respectively. In 14 of 16 lymphoma subtypes, the male-to-female IRRs were greater than 1, showing male predominance. Nodular lymphocyte predominant Hodgkin lymphoma, Burkitt lymphoma, mantle cell lymphoma, and hairy cell leukemia had the highest IRRs. Primary mediastinal B-cell lymphoma was more common in women, and marginal zone lymphoma was equally common in men and women.

Men demonstrated higher mortality in most lymphoma types, but statistically significant EMRs were only seen in cHL (1.26), aggressive lymphoma not otherwise specified (1.29), and small lymphocytic lymphoma (SLL; 1.52). Both the incidence and male predominance of lymphoma subtypes was fairly stable over the course of the study period.

The Danish data included 23,794 cases in the same number of patients—13,280 (55.8%) in men and 10,514 (44.2%) in women. LBCL, FL, SLL and cHL were the most common subtypes, and the sex distribution was found similar to the Swedish data. Male-to-female IRRs higher than 1 were seen across all subtypes in the Danish data, and most subtypes showed excessive mortality in men compared with women.

“Due to low numbers of cases and deaths, the study was probably underpowered to detect small sex differences in excess mortality in rare lymphoma subtypes,” the authors wrote. “To increase power, we plan to conduct detailed subtype-specific studies using pooled data from multiple countries and include variables like treatment, stage, performance status, comorbidity burden, and socioeconomic factors to provide a more detailed understanding of sex differences in lymphoma survival.”

Despite study limitations, the large data volume and nationwide design were significant strengths. Both the Swedish and Danish data showed a higher risk of lymphoma and a trend toward worse survival outcomes in men over the last 2 decades, adding to previous data suggesting similar trends. Further studies could provide insight into the reasoning behind these differences in risk and survival.

Reference

Radkiewicz C, Bruchfeld JB, Weibull CE, et al. Sex differences in lymphoma incidence and mortality by subtype: a population-based study. Am J Hematol. Published online September 30, 2022. doi:10.1002/ajh.26744