Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2016

01-08-2016 | Breast Oncology

Genetic Determinants of Nipple Aspiration Fluid Yield

Authors: Ali Shidfar, MD, Jun Wang, PhD, Elliot Wiesenfeld, BS, Wei Zhang, PhD, Denise Scholtens, PhD, Angela Fought, MS, Robert T. Chatterton, PhD, Seema A. Khan, MD

Published in: Annals of Surgical Oncology | Issue 8/2016

Login to get access

Abstract

Purpose

Nipple aspiration fluid (NAF) is a non-invasively-acquired biosample that can provide a window into the breast environment, but NAF yield is highly variable. Its determinants must be better understood for studies of breast cancer risk. The wet earwax phenotype was identified as one determinant of NAF yield in the 1970s, and is linked to single nucleotide polymorphisms (SNPs) in the ATP-binding cassette transporter gene ABCC11. We have investigated this, as well as SNPs in the prolactin (PRL) and prolactin receptor (PRLR) genes, in relation to NAF yield.

Methods

DNA was extracted from white blood cells of 557 NAF yielders and 359 non-yielders, and was used to genotype ABCC11 (rs17822931), PRL (rs849870, rs849872, rs849886, rs2244502, rs1341239), and PRLR (rs37364, rs34024951, rs1610218, rs9292575, rs7718468) using Taqman genotyping assay. The association between NAF yield and each single SNP was analyzed using logistic regression adjusting for age, race, and menopausal status.

Results

ABCC11 rs17822931 showed a negative association with NAF yield [odds ratio (OR) 0.66, 95 % confidence interval (CI) 0.49–0.88; p = 0.004]. The PRL rs849870 and the haplotype combination with other SNPs showed a marginal association with NAF yield. In addition, the years since last birth also showed negative association with NAF yielding (OR 0.98, 95 % CI 0.96–0.99; p = 0.001). The combination of the years since last birth with ABCC11 SNP revealed significant interaction between reproductive factor and genetic factor.

Conclusions

Our results confirmed the association between NAF yield and earwax phenotype through ABCC11 genotype. Combined with the recency of last birth, ABCC11 genotype should be considered in the design of studies utilizing NAF as a biosample.
Appendix
Available only for authorised users
Literature
1.
Reid SE, Murthy MS, Kaufman M, Scanlon EF. Endocrine and paracrine hormones in the promotion, progression and recurrence of breast cancer. Br J Surg. 1996;83:1037–46.CrossRefPubMed
2.
Khan SA, Chatterton RT Jr. Cellular and hormonal content of breast nipple aspirate fluid in relation to the risk of breast cancer. Biomark Med. 2008;2:479–93.CrossRefPubMed
3.
Alexander H, Stegner AL, Wagner-Mann C, et al. Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clin Cancer Res. 2004;10:7500–10.CrossRefPubMed
4.
Wrensch MR, Petrakis NL, Miike R, et al. Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid. J Natl Cancer Inst. 2001;93:1791–98.CrossRefPubMed
5.
Petrakis NL. ASPO distinguished achievement award lecture. Studies on the epidemiology and natural history of benign breast disease and breast cancer using nipple aspirate fluid. Cancer Epidemiol Biomarkers Prev. 1993;2:3–10.
6.
Sauter ER, Ross E, Daly M, et al. Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk. Br J Cancer. 1997;76:494–501.CrossRefPubMedPubMedCentral
7.
Petrakis NL, Mason L, Lee R, et al. Association of race, age, menopausal status, and cerumen type with breast fluid secretion in nonlactating women, as determined by nepple aspiration. J Natl Cancer Inst. 1975;54:829–34.PubMed
8.
Wrensch MR, Petrakis NL, Gruenke LD, et al. Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review. Breast Cancer Res Treat. 1990;15:39–51.CrossRefPubMed
9.
Fought AJ, McGathey C, Scholtens DM, et al. Hormonal determinants of nipple aspirate fluid yield among breast cancer cases and screening controls. Cancer Epidemiol Biomark Prev. 2013;22:2277–84.CrossRef
10.
Yoshiura K, Kinoshita A, Ishida T, et al. A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet. 2006;38:324–30.CrossRefPubMed
11.
Lee SA, Haiman CA, Burtt NP, et al. A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the multiethnic cohort. BMC Med Genet. 2007;8:72.CrossRefPubMedPubMedCentral
12.
Mong FY, Kuo YL, Liu CW, et al. Association of gene polymorphisms in prolactin and its receptor with breast cancer risk in Taiwanese women. Mol Biol Rep. 2011;38:4629–36.CrossRefPubMed
13.
Nyante SJ, Faupel-Badger JM, Sherman ME, et al. Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland. Breast Cancer Res. 2011;13:R42.CrossRefPubMedPubMedCentral
14.
Vaclavicek A, Hemminki K, Bartram CR, et al. Association of prolactin and its receptor gene regions with familial breast cancer. J Clin Endocrinol Metab. 2006;91:1513–19.CrossRefPubMed
15.
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMed
16.
17.
Petrakis NL, Ernster VL, Sacks ST, et al. Epidemiology of breast fluid secretion: association with breast cancer risk factors and cerumen type. J Natl Cancer Inst. 1981;67:277–84.PubMed
18.
Bortfeld M, Rius M, Konig J, et al. Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system. Neuroscience. 2006;137:1247–57.CrossRefPubMed
19.
Chen ZS, Guo Y, Belinsky MG, et al. Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005;67:545–57.CrossRefPubMed
20.
Guo Y, Kotova E, Chen ZS, et al. MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2′,3′-dideoxycytidine and 9′-(2′-phosphonylmethoxyethyl)adenine. J Biol Chem. 2003;278:29509–14.CrossRefPubMed
21.
Ota I, Sakurai A, Toyoda Y, et al. Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11. Anticancer Res. 2010;30:5189–94.PubMed
22.
Beesley J, Johnatty SE, Chen X, et al. No evidence for an association between the earwax-associated polymorphism in ABCC11 and breast cancer risk in Caucasian women. Breast Cancer Res Treat. 2011;126:235–39.CrossRefPubMed
23.
Tikk K, Sookthai D, Johnson T, et al. Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort. Ann Oncol. 2014;25:1422–28.CrossRefPubMed
24.
Suijkerbuijk KP, van der Wall E, Meijrink H, et al. Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer. Fam Cancer. 2010;9:321–25.CrossRefPubMedPubMedCentral
25.
Zhang L, Shao ZM, Beatty P, et al. The use of oxytocin in nipple fluid aspiration. Breast J. 2003;9:266–68.CrossRefPubMed
26.
Huang Y, Anderson KE, Nagamani M, et al. Dietary intake of lactose as a strong predictor for secretor status of nipple aspirate fluid in healthy premenopausal nonlactating women. Clin Cancer Res. 2008;14:1386–92.CrossRefPubMedPubMedCentral
Metadata
Title
Genetic Determinants of Nipple Aspiration Fluid Yield
Authors
Ali Shidfar, MD
Jun Wang, PhD
Elliot Wiesenfeld, BS
Wei Zhang, PhD
Denise Scholtens, PhD
Angela Fought, MS
Robert T. Chatterton, PhD
Seema A. Khan, MD
Publication date
01-08-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5163-x

Other articles of this Issue 8/2016

Annals of Surgical Oncology 8/2016 Go to the issue

Gastrointestinal Oncology

Is there a Benefit of Multidisciplinary Cancer Team Meetings for Patients with Gastrointestinal Malignancies?

Pancreatic Tumors

Laparoscopic Pancreaticoduodenectomy with Reconstruction of the Portal Vein with the Parietal Peritoneum

Breast Oncology

Late Axillary Recurrence After Negative Sentinel Lymph Node Biopsy is Uncommon

Head and Neck Oncology

Results and Survival of Locally Advanced AJCC 7th Edition T4a Laryngeal Squamous Cell Carcinoma Treated with Primary Total Laryngectomy and Postoperative Radiotherapy

Hepatobiliary Tumors

Defining Surgical Difficulty According to the Perceived Complexity of Liver Resection: Validation of a Complexity Classification in Patients with Hepatocellular Carcinoma

Breast Oncology

Post-mastectomy Radiation: Should Subtype Factor into the Decision?