Tuya Pal, MD

Dr. Pal's epidemiology-based cancer genetics research has two foci: identification of individuals with genetic and environmental risk factors that place them at increased risk of developing cancer, and development of strategies to reduce this risk. Her currently active research includes studies on ovarian cancer and mismatch repair deficiency and on genetic and hormonal risk factors for breast cancer in African American women. One of the best defined molecular pathways involved in both inherited and sporadic cancer pathogenesis involves the mismatch repair (MMR) pathway, which leads to microsatellite instability (MSI).  MSI may result from both genetic (i.e.: germline mutations in the MMR genes, including MLH1, MSH2, and MSH6) and epigenetic (i.e.: MLH1 promoter hypermethylation) mechanisms.  The purpose of the ‘Ovarian Cancer and Mismatch Repair Deficiency’ study is to quantify the proportion of ovarian tumors due to the mismatch repair genes and to characterize the tumors in this group.   Our ability to classify ovarian cancers by their genetic basis offers promise for improvements in cancer prevention and screening of high risk women, in basing diagnosis and prognosis on molecular markers, and in development of individualized treatments.  This study will include 2200 population-based cases of incident epithelial ovarian cancers based at the Moffitt Cancer Center, Duke Comprehensive Cancer Center, and the University of Toronto. Paraffin-embedded tumor samples will be analyzed from all subjects with incident ovarian cancers to perform MSI testing and investigate MMR gene protein expression.  In those samples with MSI-H status or with loss of expression of MMR gene proteins, epigenetic (MLH1 promoter hypermethylation) and genetic (germline MMR mutations) will be investigated.Although African American women have a lower overall incidence of breast cancer than Caucasian women, the incidence of early-onset breast cancer is actually higher in African Americans. There is strong evidence that breast cancer in premenopausal women has a significant genetic component. In some cases, the genetic component may be attributable to high-penetrance genes such as BRCA1 and BRCA2; in others, to lower penetrance genes. Most of the low-penetrance genes thus far implicated in increased breast cancer risk are involved in hormone metabolism. Dr. Pal is investigating the contribution of high-penetrance BRCA1/BRCA2 genes in young African American breast cancer patients with a personal or family history suggestive of hereditary predisposition. This study will improve our understanding of inherited breast cancer in young African American women.

• Pal T, Cragun D, Lewis C, Doty A, Rodriguez M, Radford C, Thompson Z, Kim J, Vadaparampil ST. A statewide survey of practitioners to assess knowledge and clinical practices regarding hereditary breast and ovarian cancer. Genet Test Mol Biomarkers. 2013 May;17(5):367-375. Pubmedid: 23448386.
• Pal T, Vadaparampil S, Kim J, Xu Y, Friedman S, Narod SA, Metcalfe K. Interest of individuals from BRCA families to participate in research studies focused on male BRCA carriers. Fam Cancer. 2013 Mar. Pubmedid: 23504063.
• Pal T, Bonner D, Kim J, Monteiro AN, Kessler L, Royer R, Narod SA, Vadaparampil ST. Early Onset Breast Cancer in a Registry-based Sample of African-American Women: BRCA Mutation Prevalence, and Other Personal and System-level Clinical Characteristics. Breast J. 2013 Mar;19(2):189-192. Pubmedid: 23320992.
• Pal T, Lee JH, Besharat A, Thompson Z, Monteiro A, Phelan C, Lancaster J, Metcalfe K, Sellers T, Vadaparampil S, Narod S. Modes of delivery of genetic testing services and the uptake of cancer risk management strategies in BRCA1 and BRCA2 carriers. Clin Genet. 2013 Feb. Pubmedid: 23438721.
• McLaughlin JR, Rosen B, Moody J, Pal T, Fan I, Shaw PA, Risch HA, Sellers TA, Sun P, Narod SA. Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2. J Natl Cancer Inst. 2013 Jan;105(2):141-148. Pubmedid: 23257159. Pmcid: PMC3611851.
• Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA. Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. Br J Cancer. 2012 Nov;107(10):1783-1790. Pubmedid: 23047549. Pmcid: PMC3493867.
• Coppola D, Nicosia SV, Doty A, Sellers TA, Lee JH, Fulp J, Thompson Z, Galeb S, McLaughlin J, Narod SA, Schildkraut J, Pal T. Uncertainty in the utility of immunohistochemistry in mismatch repair protein expression in epithelial ovarian cancer. Anticancer Res. 2012 Nov;32(11):4963-4969. Pubmedid: 23155266.
• Pal T, Vadaparampil ST. Genetic risk assessments in individuals at high risk for inherited breast cancer in the breast oncology care setting. Cancer Control. 2012 Oct;19(4):255-266. Pubmedid: 23037493.
• Vadaparampil ST, Christie J, Quinn GP, Fleming P, Stowe C, Bower B, Pal T. A pilot study to examine patient awareness and provider discussion of the impact of cancer treatment on fertility in a registry-based sample of African American women with breast cancer. Support Care Cancer. 2012 Oct;20(10):2559-2564. Pubmedid: 22270090.
• Cragun D, Malo TL, Pal T, Shibata D, Vadaparampil ST. Colorectal cancer survivors' interest in genetic testing for hereditary cancer: implications for universal tumor screening. Genet Test Mol Biomarkers. 2012 Jun;16(6):493-499. Pubmedid: 22224634. Pmcid: PMC3378022.
• Quinn GP, Pal T, Murphy D, Vadaparampil ST, Kumar A. High-risk consumers' perceptions of preimplantation genetic diagnosis for hereditary cancers: a systematic review and meta-analysis. Genet Med. 2012 Feb;14(2):191-200. Pubmedid: 22261755.
• Quinn GP, Pal T, Murphy D, Vadaparampil ST, Kumar A. High-risk consumers' perceptions of preimplantation genetic diagnosis for hereditary cancers: A systematic review and meta-analysis. Genet Med. 2011 Sep. Pubmedid: 21918462.
• Pal T, Rocchio E, Garcia A, Rivers D, Vadaparampil S. Recruitment of black women for a study of inherited breast cancer using a cancer registry-based approach. Genet Test Mol Biomarkers. 2011 Jan-Feb;15(1-2):69-77. Pubmedid: 21117951.
• Vadaparampil ST, Quinn GP, Gjyshi A, Pal T. Development of a brochure for increasing awareness of inherited breast cancer in black women. Genet Test Mol Biomarkers. 2011 Jan-Feb;15(1-2):59-67. Pubmedid: 21275654.
• Pal T, Stowe C, Cole A, Lee JH, Zhao X, Vadaparampil S. Evaluation of phone-based genetic counselling in African American women using culturally tailored visual aids. Clin Genet. 2010 Aug;78(2):124-131. Pubmedid: 20662853.
• Daly MB, Axilbund JE, Buys S, Crawford B, Farrell CD, Friedman S, Garber JE, Goorha S, Gruber SB, Hampel H, Kaklamani V, Kohlmann W, Kurian A, Litton J, Marcom PK, Nussbaum R, Offit K, Pal T, Pasche B, Pilarski R, Reiser G, Shannon KM, Smith JR, Swisher E, Weitzel JN. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Canc Netw. 2010 May;8(5):562-594. Pubmedid: 20495085.
• Pal T, Keefe D, Sun P, Narod SA. Fertility in women with BRCA mutations: a case-control study. Fertil Steril. 2010 Apr;93(6):1805-1808. Pubmedid: 19200971.
• Permuth-Wey J, Vadaparampil S, Rumphs A, Kinney AY, Pal T. Development of a culturally tailored genetic counseling booklet about hereditary breast and ovarian cancer for Black women. Am J Med Genet A. 2010 Apr;152A(4):836-845. Pubmedid: 20358592.
• Permuth-Wey J, Boulware D, Valkov N, Livingston S, Nicosia S, Lee JH, Sutphen R, Schildkraut J, Narod S, Parker A, Coppola D, Sellers T, Pal T. Sampling strategies for tissue microarrays to evaluate biomarkers in ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):28-34. Pubmedid: 19124477. Pmcid: PMC2664171.
• Pal T, Permuth-Wey J, Kumar A, Sellers TA. Systematic review and meta-analysis of ovarian cancers: estimation of microsatellite-high frequency and characterization of mismatch repair deficient tumor histology. Clin Cancer Res. 2008 Nov;14(21):6847-6854. Pubmedid: 18980979. Pmcid: PMC2655731.
• Pal T, Vadaparampil S, Betts J, Miree C, Li S, Narod SA. BRCA1/2 in high-risk African American women with breast cancer: providing genetic testing through various recruitment strategies. Genet Test. 2008 Sep;12(3):401-407. Pubmedid: 18752448.
• Pal T, Permuth-Wey J, Sellers TA. A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer. Cancer. 2008 Aug;113(4):733-742. Pubmedid: 18543306. Pmcid: PMC2644411.
• Chu W, Fyles A, Sellers E, McCready D, Murphy J, Pal T, Narod S. Association between CYP3A4 genotype and risk of endometrial cancer following tamoxifen use. Carcinogenesis. 2007 Oct;28(10):2139-42. Pubmedid: 17434921.
• Pal T, Napierala D, Becker T, Loscalzo M, Baldridge D, Lee B, Sutphen R. The presence of germ line mosaicism in cleidocranial dysplasia. Clin Genet. 2007 Jun;71(6):589-591. Pubmedid: 17539909.
• Pal T, Permuth-Wey J, Kapoor R, Cantor A, Sutphen R. Improved survival in BRCA2 carriers with ovarian cancer. Fam Cancer. 2007;6(1):113-119. Pubmedid: 17160431. Pmcid: PMC3303221.
• Beiner M, Rosen B, Fyles A, Harley I, Pal T, Siminovitch K, Zhang S, Sun P, Narod S. Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(9):1636-1640. Pubmedid: 16985024.
• Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, LaPolla J, Hoffman M, Martino MA, Wakeley K, Wilbanks G, Nicosia S, Cantor A, Sutphen R. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005 Dec;104(12):2807-2816. Pubmedid: 16284991.
• Sellers T, Schildkraut J, Pankratz V, Vierkant R, Fredericksen Z, Olson J, Cunningham J, Taylor W, Liebow M, McPherson C, Hartmann L, Pal T, Adjei A. Estrogen bioactivation, genetic polymorphisms, and ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11Pt1):2536-2543. Pubmedid: 16284375.
• Pal T, Permuth-Wey J, Holtje T, Sutphen R. BRCA1 and BRCA2 mutations in a study of African American breast cancer patients. Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1794-1799. Pubmedid: 15533909.
• Thiffault I, Hamel N, Pal T, McVety S, Marcus V, Farber D, Cowie S, Deschenes J, Meschino W, Odefrey F, Goldgar D, Graham T, Narod S, Watters A, MacNamara E, Sart D, Chong G, Foulkes W. Germline truncating muations in both MSH2 and BRCA2 in a single kindred. Br J Cancer. 2004;90(2):483-491. Pubmedid: 14735197.
• Pal T, Sutphen R, Sellers T. Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma. Cancer. 2004;100(11):2485-2486. Pubmedid: 15160358.
• Elliot A, Graham J, Curry C, Pal T, Rimoin D, Lachman R. Spectrum of dolichospondylic dysplasia: two new patients with distinctive findings. Am J Med Genet. 2002;113(4):351-361. Pubmedid: 12457407.
• Elit L, Pal T, Goshen R, Jernstrom H, Ackerman I, Fyles A, Carey M, Mitchell M, Aube J, Narod S. Familial and hormonal risk factors for papillary serous uterine cancer. Eur J Gynaecol Oncol. 2002;23(3):187-190. Pubmedid: 12094951.
• Pal T, Vogl F, Chappuis P, Tsang R, Brierley J, Renard H, Sanders K, Kantemiroff T, Bagha S, Goldgar D, Narod S, Foulkes W. Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study. J Clin Endocrinol Metab. 2001;86(11):5307-5312. Pubmedid: 11701697.
• Pal T, Hamel N, Vesprini D, Sanders K, Mitchell M, Quercia N, Ng C, Murray A, Foulkes W, Narod S. Double primary cancers of the breast and thyroid in women: molecular analysis and genetic implications. Familial Cancer. 2001;1(1):17-24. Pubmedid: 14574011.
• Pal T, Liede A, Mitchell M, Calender A, Narod S. Intestinal carcinoid tumours in a father and daughter. Can J Gastroenterol. 2001;15(6):405-409. Pubmedid: 11429670.
• Pal T, Liede A, Mitchell M, Calendar A, Narod S. Occurrence of intestinal carcinoid tumours in a father and daughter. Gastroenterologist. 2001;15(6):405-409. Pubmedid: no pub med.
• Narod S, Pal T, Staples T, Mitchell M, Fyles A. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer [correspondence]. Lancet. 2001;357:65-66. Pubmedid: No pub med.
• Bevan S, Pal T, Greenberg C, Green H, Wixey J, Bignell G, Narod S, Foulkes W, Stratton M, Houlston R. A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: confirmation of linkage to TCO1. J Clin Endocrinol Metab. 2001;86(8):3701-3704. Pubmedid: 11502798.
• Goshen R, Chu W, Elit L, Pal T, Hakimi J, Ackerman I, Fyles A, Mitchell M, Narod S. Is uterine papillary serous adenocarcinoma a manifestation of the hereditary breast-ovarian cancer syndrome?. Gynecol Oncol. 2000;79(3):477-481. Pubmedid: 11104623.
• Charames G, Millar A, Pal T, Narod S, Bapat B. Do MSH6 mutations contribute to double primary cancers of the colorectum and endometrium?. Hum Genet. 2000;107(6):623-629. Pubmedid: 11153917.
• Liede A, Pal T, Mitchell M, Narod S. Delineation of a new syndrome: clustering of pyloric stenosis, endometriosis, and breast cancer in two families. J Med Genet. 2000;37(10):794-796. Pubmedid: 11183186.
• Millar A, Pal T, Madlensky L, Sherman C, Temple L, Mitri A, Cheng H, Marcus V, Gallinger S, Bapat B, Narod S. Mismatch repair gene defects contribute to the genetic basis of double primary cancers of the colorectum and endometrium. Hum Mol Genet. 1999;8(5):823-829. Pubmedid: 10196371.
• Pal T, Flanders T, Mitchell-Lehman M, MacMillan A, Brunet J, Narod S, Foulkes W. Genetic implications of double primary cancers of the colorectum and endometrium. J Med Genet. 1998;35(12):978-984. Pubmedid: 9863592.