Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis

Abstract

Background: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. Objective: To identify and evaluate current evidence on maternal exposure to cigarette smoke during pregnancy and testicular cancer in offspring. Methods: A systematic search of English peer-reviewed original literature in PubMed through a block search approach. Publications were considered if assessing maternal exposure to cigarette smoke and the risk of testicular cancer in offspring. Results: Among the 636 identified records, 14 publications were eligible for review and 10 for meta-analysis. Quality assessment of the publications was conducted. Most included publications were case-control studies (n = 11, 79%), while the remaining were ecological studies (n = 3, 21%). Completeness of reporting was high, but more than half were considered subject to potential bias. The trend synthesis showed that half (n = 7) of the included publications demonstrated a higher risk of testicular cancer in the sons of mothers exposed to cigarette smoke during pregnancy. The meta-analysis generated an overall summary risk estimate of 1.00 (95% CI: 0.88; 1.15) (n = 10 publications), with a lower risk for seminoma (0.79, 95% CI: 0.59; 1.04) and nonseminoma (0.96, 95% CI: 0.74; 1.26) (n = 4 publications). Conclusions: This systematic review did not provide evidence of an association between maternal exposure to cigarette smoke and risk of testicular cancer in offspring. An overall positive trend was suggested, but it had low statistical precision. The methodological limitations across publications encourage further research based on valid exposure data.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case‐control study

“…Almost three decades ago, Clemmesen proposed that maternal smoking in pregnancy may be a cause of testicular germ cell cancer 7 . But in a recent review of available literature, we did not find evidence supporting an association 8 . Importantly, only one study has assessed cotinine in maternal serum as a marker of tobacco exposure during pregnancy 9 .…”

“…Of note, no clear dose‐response relationships were observed for the four tobacco exposure groups, which reduces confidence in identifying a causal relationship. Other studies investigating the association have been susceptible to information and recall bias with the use of self‐reported exposure data, 8 thereby challenging the comparison of these findings, due to having demonstrated both increased, 19‐25 decreased 9,26,27 or no changed 28‐31 risk of testicular cancer in offspring. Few studies have investigated histological subtypes of testicular cancer and in line with our present study, none achieved robust results 9,22,27,28 …”

“…7 But in a recent review of available literature, we did not find evidence supporting an association. 8 Importantly, only one study has assessed cotinine in maternal serum as a marker of tobacco exposure during pregnancy. 9 Investigating cotinine in amniotic fluid may be of particular interest due to its direct interaction with the fetus, though not previously assessed in this context.…”