Page 88 - New epidemiological and PSMA-expression based paradigms in salivary gland tumors

Chapter 5
SGC (SIR 1.07; 95% CI 0.72-1.53)[27]. This absence of an increased risk could have been caused by differences in inclusion, by including lesions of undefined histology (overall 25%) as a first tumor. These could have been metastases of e.g. squamous cell carcinoma of the skin of the face or skull to the parotid, which could have attenuated a higher risk of BC.
Table 4. A comparison of publications investigating breast cancer (BC) incidence in women after diagnosis of a salivary gland tumor (SGT).
Ref, year
[21], 1968 [22], 1969 [23], 1972 [24], 1977 [25], 1983 [26], 1984 [27], 1999 [28], 2005 Current,
2019
Women SGT (n) (M/B)
396 M 297 M 349 M 453 M+B 367 M 190 M+B 1718 M* 439 M+B
2083 B 1567 M
Years at risk
1,652
3,033
2,443
2,315
2,868
629
10,789
3,382
18,852 10,995
Observed Expected O/E BC BC (SIR)
7 0.9 7.8
4 4.0 1.0
8 4.2 1.9
6 2.6 2.3
7 5.4 1.3
4 0.83 4.8
30 28 1.07
15 5.93 2.5
74 50 1.48 52 32.6 1.59
P value
0.00004 NA 0.6 <0.05 NR 0.01 NR 0.003 NR
NR
95% CI
NR
NA
NR
NR
0.5-2.7
NR
0.72-1.53
1.4-4.2
1.16-1.86 1.19-2.09
86
M = malignant; B = benign; NA = not applicable; NR = not reported; *25% undetermined / mixed histology and 13% squamous cell carcinoma
The increased risk of BC after a salivary gland tumor in our nationwide cohorts, is of similar magnitude as some of the known risk factors, such as alcohol intake or use oral contraceptives (Supplementary table 1) and is remarkable. It could theoretically be caused by several mechanisms.
Common endocrine mechanism and common environmental / lifestyle factors: A positive association between (high levels of) endogenous estrogens or estrogen exposure and risk of various female cancers (breast, ovarian and endometrial cancer) has been consistently described in the epidemiological literature[35–38]. Estrogens are thought to cause this increased cancer risk via cell proliferation, DNA-damage (as a result of estradiol metabolism to genotoxic metabolites) and inhibition of cell repair mechanisms[39]. Estrogen exposure may have similar effects on salivary glandular tissue, which also expresses estrogen receptors. It could therefore be that women with high endogenous estrogen levels (e.g. in post- menopausal high BMI) or exposure (e.g. in postmenopausal hormone replacement therapy or use of oral contraceptives) have an increased risk of SGC or SGPA[40– 44]. If estrogen indeed has an effect on both risk of SGC and risk of SGPA,