Page 90 - New epidemiological and PSMA-expression based paradigms in salivary gland tumors

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Chapter 5
pedigrees, reported 3 SGCs[58]. Although the authors reported an increased SGC incidence, a 95% CI was not provided. Mersch and colleagues did not find any SGC in 1,072 patients with a BRCA1 or BRCA2 mutation, who had received genetic counselling[59]. In a study of 268 patients with SGPA, upon evaluation for BRCA1, one had a BRCA1 mutation (who earlier also had BC)[60]. Other forms of genetic predisposition i.e. based on (multiple) single-nucleotide polymorphisms (SNPs) have not been reported. Although SGPA is characterized by a chromosomal translocation that causes activation of the pleomorphic adenoma gene 1 (PLAG1) on chromosome 8q12, germline mutations have not yet been identified[61–65].
Limitations: Although the results of this study suggest that salivary gland tumors and BC share a common (hormonal) etiological factor, further investigation will be needed to provide more insight in the underlying mechanism. It is still unclear whether affected women who develop both a salivary gland tumor and BC are e.g. more susceptible for the effect of estrogens, have higher blood levels or have had more estrogen exposure. Data on BC risk factors were unavailable as these are not routinely collected by the Dutch cancer registry.
Person time after an SGPA diagnosis was not available and imputed assuming these patients had a similar life expectancy as the general Dutch population. SGPA does carry a very small risk of malignant transformation of approximately 0.15%, which may lead to a slightly higher mortality than that of the general population[2]. We may thus have overestimated the follow-up in the SGPA cohort, which would have resulted in slight overestimation of the expected number of BC cases[2], and subsequently an underestimation of the SIR for BC. On the other hand, follow-up of SGC patients is very complete, with information on dates of death or migration provided by linkage with the Dutch nationwide population registry, and near complete information on BCs occurring in this cohort, available from the same source.
In summary, there are some indications that suggest an endocrine mechanism behind the increased incidence of BC in salivary gland tumors. Data on a possible genetic background are insufficient. Sequencing of the cohorts for possible germline mutations might provide further clues regarding genetic predisposition, but this would require very large cohorts.