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Epidemiology:
doi: 10.1097/EDE.0b013e3181aff37c
Letters to the Editor

Childbearing and Salivary Gland Cancer: A Population-based Nested Case–control Study

Lu, Yunxia; Lagergren, Jesper; Eloranta, Sandra; Lambe, Mats

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Yunxia.Lu@ki.se (Lu)

Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (Lagergren)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Eloranta)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Regional Oncologic Centre, Uppsala University Hospital, Uppsala, Sweden (Lambe)

Supported by the Swedish Cancer Society, grant 07 0129.

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To the Editor:

Salivary gland cancer is a rare cancer group with a largely unknown etiology. Several lines of indirect evidence indicate a role of sex hormones in its development: (1) salivary duct carcinoma (one histologic type of salivary gland cancer) has morphologic and biologic characteristics resembling high-grade mammary ductal carcinoma1; (2) expression of several hormones has been detected in salivary gland cancers1–3; (3) steroid-hormone-receptor status might influence salivary gland cancer progression2–4; (4) risk factors for salivary gland cancer among women bear similarities to female cancers of the breast, endometrium, and ovary5; and (5) women with salivary gland cancer before age 35 might be at an increased risk of breast cancer.6,7

The rarity of salivary gland cancer has prohibited studies of the possible etiologic role of hormonal factors. To our knowledge, only one study to date has addressed possible associations between reproductive factors and the risk of salivary gland cancer.5 Using information from large Swedish population-based registers, we initiated a 1:5-matched nested case–control study among women born between 1 January 1932 and 31 December 2003. The possible influence of parity, maternal age at first birth and time since most recent delivery were evaluated in relation to risk of salivary gland cancer. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 460 cases of salivary gland cancer and 2300 controls were included. Main results are shown in the Table. Compared with a history of uniparity, multiparity did not seem to influence the risk of salivary gland cancer, and there were no material differences between women younger or older than 50 years at diagnosis. There was a possible inverse association between older age at first birth and risk of salivary gland cancer. The OR was 0.66 (CI = 0.40–1.11) among women with a first birth at age 30 or older compared with those who gave birth before age 20. Based on the point estimates, this possible inverse relation seemed stronger in the postmenopausal group than in the premenopausal group. There were no apparent changes in risk depending on the time since most recent birth.

TABLE. Associations ...
TABLE. Associations ...
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The present study did not identify important associations between parity, age at first delivery, time since most recent birth and the risk of developing salivary gland cancer. There were, however, some indications of a protective effect of older maternal age at first birth that seemed more pronounced in postmenopausal women.

A possibly inverse association between older maternal age at first birth is in agreement with a previous case–control study on salivary gland cancer.5 While opposite from the pattern observed for breast cancer, a protective effect of older age at first birth have been observed for endometrial and ovarian cancer. There is some biologic evidence supporting hormonal influences in the etiology of salivary gland cancer. For example, salivary duct carcinoma, shows a striking histopathologic resemblance to ductal carcinoma of the breast and also the presence of sex steroids and the receptor for progesterone was demonstrated.1,2,4 However, because the incidence of salivary duct carcinoma is very low (representing only 5% of the total number of salivary gland cancers), the study did not have statistical power to evaluate this subgroup separately.

In conclusion, in the present population-based study, we found no associations between parity, older maternal age at first birth, or time since recent delivery and risk of developing salivary gland cancer. A possible protective effect of older maternal age at first birth might, however, exist. Further studies are warranted based on larger numbers of subjects and enabling analyses of histologic subtypes of salivary gland cancer.

Yunxia Lu

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Yunxia.Lu@ki.se

Jesper Lagergren

Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Sandra Eloranta

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Mats Lambe

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Regional Oncologic Centre, Uppsala University Hospital, Uppsala, Sweden

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REFERENCES

1.Williams MD, Roberts D, Blumenschein GR Jr, et al. Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients. Am J Surg Pathol. 2007;31:1645–1652.

2.Shick PC, Riordan GP, Foss RD. Estrogen and progesterone receptors in salivary gland adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;80:440–444.

3.Ozono S, Onozuka M, Sato K, Ito Y. Immunohistochemical localization of estradiol, progesterone, and progesterone receptor in human salivary glands and salivary adenoid cystic carcinomas. Cell Struct Funct. 1992;17:169–175.

4.Teymoortash A, Lippert BM, Werner JA. Steroid hormone receptors in parotid gland cystadenolymphoma (Warthin's tumour). Clin Otolaryngol Allied Sci. 2001;26:411–416.

5.Horn-Ross PL, Morrow M, Ljung BM. Menstrual and reproductive factors for salivary gland cancer risk in women. Epidemiology. 1999;10:528–530.

6.Sun EC, Curtis R, Melbye M, Goedert JJ. Salivary gland cancer in the United States. Cancer Epidemiol Biomarkers Prev. 1999;8:1095–1100.

7.In der Maur CD, Klokman WJ, van Leeuwen FE, Tan IB, Rutgers EJ, Balm AJ. Increased risk of breast cancer development after diagnosis of salivary gland tumour. Eur J Cancer. 2005;41:1311–1315.

© 2009 Lippincott Williams & Wilkins, Inc.

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