Incidence of Salivary Gland Tumors among Atomic Bomb Survivors, 1950-1987. Evaluation of Radiation-Related Risk

Abstract

A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR1Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR1Sv = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR1Sv = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR1Sv = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR1Sv = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study.

The absence of significant mutational events of the p53 gene in the only two salivary gland tumors possessing radiation-related development risks, mucoepidermoid carcinoma and Warthin tumor

“…In the present study, however, we found p53 mutational points in Warthin tumor cases which were highly shared among the sample group, although those point mutations did not affect the amino acid translation so much, indicating that they were just genetic polymorphisms. As shown in the sequencing (14,42). The present data indicate a possibility that immunological or inflammatory stimuli tend to be associated with some intrinsic background such as p53 gene polymorphisms in the pathogenesis of Warthin tumor.…”

“…Together with Warthin tumors, mucoepidermoid carcinomas have been shown to be related to radiation in their pathogenesis (14)(15). Therefore, these two tumors were simply expected to share certain common gene mutational backgrounds caused by radiation.…”

“…Another line of evidence reported for salivary gland tumorigenesis is the later effect of exposure to ionizing radiation by atomic bombs (4-7) and therapeutic radiation (8)(9)(10)(11)(12)(13). Based on the survey of atomic bomb survivors in Hiroshima and Nagasaki, Japan, we have already found a causal role for ionizing radiation in salivary gland tumorigenesis, particularly in mucoepidermoid carcinomas and Warthin tumors, incidences of which were shown to be dependent on the radiation doses (14)(15).…”

Malignant tumors of the major salivary glands among the population of the city of Belgrade

“…Radno okruženje u drvnoj industriji i industriji prerade guma kao i prisustvo silikonske prašine dovodi se u vezu sa nastankom malignih tumora pljuvačnih žlezda [5]. Postoje indicije da izlaganje ultraljubičastoj [24] ili jonizujućoj radijaciji [25,26] može povećati rizik od nastanka karcinoma pljuvačnih žlezdi. Kumulativno izlaganje opisanim faktorima može objasniti učestalost ovih karcinoma u kasnijem životnom dobu.…”

Emerging Biology of Malignant Salivary Gland Tumors Offers New Insights into the Classification and Treatment of Mucoepidermoid Cancer

“…Other rare mucoepidermoid cancer^like tumors that can arise from several different organ sites have not yet been tested for the presence of the fusion oncogene. B, mapping of the t(11;19) chromosomal breakpoint, which occurs within intron 1of both the Mect1/Torc1 and Maml2 genes in all cases tested and which results in exon 1 swapping between the genes.Whereas the etiologic events leading to the t(11;19) are unknown in most cases, mucoepidermoid cancer presents commonly as a secondary cancer in children and shows an exceptionally strong radiation dose response risk (30,31 Taken together, these reports allow us to make several predictions and speculations. First, we can now recognize that high-grade or poorly differentiated mucoepidermoid cancer is a distinct genetic entity from low-grade malignancies.…”