Cancer risk in first- and second-degree relatives of men with poor semen quality

Abstract

Objective: To further characterize the association of male infertility with health risks by evaluating semen quality and cancer risk in family members.

Design: Retrospective, cohort study.

Setting: Not applicable.

Patient(s): A total of 12,889 men undergoing SA and 12,889 fertile control subjects that had first-degree relative (FDR) data (n = 130,689) and 8,032 men with SA and 8,032 fertile control subjects with complete second-degree relative (SDR) data (n = 247,204) were identified through the UPDB. An equal number of fertile population control subjects were matched.

Interventions: None.

Main outcome measure(s): Adult all-site, testicular, thyroid, breast, prostate, melanoma, bladder, ovarian, and kidney cancer diagnoses in FDRs and SDRs.

Result(s): The FDRs of men with SA had a 52% increased risk of testicular cancer compared with the FDRs of fertile population control subjects. There was no significant difference in testicular cancer risk for the SDRs based on any of the semen parameters. The FDRs and SDRs of azoospermic men had a significantly increased risk of thyroid cancer compared with fertile population control subjects.

Conclusion(s): These data suggest a link between male infertility and selected cancer risk in relatives. This highlights the possibilities of shared biologic mechanisms between the two diseases, exposure to environmental factors, and an increased level of genetic and/or epigenetic burden in subfertile men and their relatives that may be associated with risk of cancer.

Keywords: Epidemiology; andrology; infertility; semen analysis; testicular cancer.

FIGURE 1

Semen analysis cohort inclusion criteria. Sample selection for the men with semen analysis. Matched fertile control subjects were selected for the final samples: 12,889 for the first-degree relative (FDR) analysis and 8,032 for the second-degree relative (SDR) analysis. Total number of FDRs and SDRs for men with semen analysis and their matched control subjects by relationship type. Total numbers of first- and second-degree relatives equal 130,689 and 247,204, respectively.

FIGURE 2

Risk of testicular cancer for first-degree relatives of men with semen analysis compared with first-degree relatives (FDRs) of fertile control subjects. (A) Concentration (model 2; a = azoospermia; o = oligozoospermia; n = normozoospermia; h = hyperzoospermia). (B) Sperm count (model 3). (C) Motility (model 4; a = azoospermia; q1 = 1st quartile, 0%–49%; q2 = 2nd quartile, 50%–59%; q3 = 3rd quartile, 60%–69%; q4 = 4th quartile, 70%–100%). (D) Total motile count (model 8). (E) Morphology (model 6). (F) Vitality (model 5; a = azoospermia; q1 =1st quartile, 0%–49%; q2 = 2nd quartile, 50%–59%; q3 = 3rd quartile, 60%–69%; q4 = 4th quartile, 70%–100%).

FIGURE 3

Risk of thyroid cancer in first-degree relatives (FDRs) of men with semen analysis compared with FDRs of fertile control subjects. (A) Concentration (model 2; a = azoospermia; o = oligozoospermia; n = normozoospermia; h = hyperzoospermia). (B) Sperm count (model 3). (C) Motility (model 4; a = azoospermia; q1 = 1st quartile, 0%–49%; q2 = 2nd quartile, 50%–59%; q3 = 3rd quartile, 60%–69%; q4 = 4th quartile, 70%–100%). (D) Total motile count (model 8). (E) Morphology (model 6). (F) Vitality (model 5; a = azoospermia; q1 = 1st quartile, 0%–49%; q2 = 2nd quartile, 50%–59%; q3 = 3rd quartile, 60%–69%; q4 = 4th quartile, 70%–100%).