Abstract
Purpose
History of keratinocyte carcinoma (KC) has been associated with survival following the diagnosis of a second primary malignancy (SPM), with the direction of the association varying by cancer type. Research is needed to elucidate the role of other key factors in this association.
Methods
A retrospective cohort study was conducted among patients newly diagnosed and/or treated at Moffitt Cancer Center in December 2008–April 2020 with breast cancer, lung cancer, melanoma, colon cancer, prostate cancer, and non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) (n = 29,156). History of KC was obtained from new patient intake questionnaires. Age- and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the association between history of KC and survival following each cancer, stratified by demographic/clinical characteristics.
Results
KC history was most prevalent in patients with melanoma (28.7%), CLL (19.8%) and lung cancer (16.1%). KC history was associated with better overall survival following prostate cancer (HR = 0.74, 95% CI = 0.55–0.99) and poorer overall survival following CLL (HR = 1.73, 95% CI = 1.10–2.71). Patients with a history of KC experienced better survival within the first four years of a melanoma diagnosis (HR = 0.79, 95% CI = 0.67–0.92); whereas poorer survival was observed for patients who survived 7 + years after a melanoma diagnosis (HR = 2.18, 95% CI = 1.17–4.05). Stratification by treatment and stage revealed directional differences in the associations between KC history and survival among patients with breast cancer and melanoma.
Conclusions
KC history may be a predictor of survival following an SPM, possibly serving as a marker of immune function and/or DNA damage repair capacity.
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Data availability
The datasets presented in this article are not readily available to protect participant confidentiality and privacy. Requests to access the datasets should be directed to the corresponding author.
References
Abbas F, El Kossi M, Shaheen IS, Sharma A, Halawa A (2020) Post-transplantation lymphoproliferative disorders: current concepts and future therapeutic approaches. World J Transplant 10(2):29–46. https://doi.org/10.5500/wjt.v10.i2.29
Alberg AJ, Fischer AH (2014) Is a personal history of nonmelanoma skin cancer associated with increased or decreased risk of other cancers? Cancer Epidemiol and Prev Biomarkers 23(3):433–436
Alberg AJ, Jorgensen TJ, Ruczinski I, Wheless L, Shugart YY, Berthier-Schaad Y, Kessing B, Hoffman-Bolton J, Helzlsouer KJ, Kao WL (2013) DNA repair gene variants in relation to overall cancer risk: a population-based study. Carcinogenesis 34(1):86–92
Al-Husseini MJ, Saad AM, Mohamed HH, Alkhayat MA, Sonbol MB, Abdel-Rahman O (2019) Impact of prior malignancies on outcome of colorectal cancer; revisiting clinical trial eligibility criteria. BMC Cancer 19(1):863. https://doi.org/10.1186/s12885-019-6074-6
Amin, M. (2017). ES, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, et al. AJCC Cancer Staging Manual (8th edition): Springer International Publishing: American Joint Commission on Cancer.
Asgari MM, Moffet HH, Ray GT, Quesenberry CP (2015) Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998–2012. JAMA Dermatol 151(9):976–981. https://doi.org/10.1001/jamadermatol.2015.1188
Askling J, Sørensen P, Ekbom A, Frisch M, Melbye M, Glimelius B, Hjalgrim H (1999) Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? Ann Intern Med 131(9):655–659. https://doi.org/10.7326/0003-4819-131-9-199911020-00004
Athas WF, Hunt WC, Key CR (2003) Changes in nonmelanoma skin cancer incidence between 1977–1978 and 1998–1999 in Northcentral New Mexico. Cancer Epidemiol Biomarkers Prev 12(10):1105–1108
Bingmer K, Ofshteyn A, Dietz DW, Stein SL, Steinhagen E (2020) Outcomes in immunosuppressed anal cancer patients. Am J Surg 219(1):88–92. https://doi.org/10.1016/j.amjsurg.2019.08.011
Bottomley MJ, Thomson J, Harwood C, Leigh I (2019) The role of the immune system in cutaneous squamous cell carcinoma. Int J Mol Sci. https://doi.org/10.3390/ijms20082009
Burgi A, Brodine S, Wegner S, Milazzo M, Wallace MR, Spooner K, Blazes DL, Agan BK, Armstrong A, Fraser S, Crum NF (2005) Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals. Cancer 104(7):1505–1511. https://doi.org/10.1002/cncr.21334
Camandaroba MPG, de Araujo RLC, Silva VSE, de Mello CAL, Riechelmann RP (2019) Treatment outcomes of patients with localized anal squamous cell carcinoma according to HIV infection: systematic review and meta-analysis. J Gastrointest Oncol 10(1):48–60. https://doi.org/10.21037/jgo.2018.10.08
Chen ST, Li X, Han J (2018) Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women. Int J Cancer 142(8):1536–1541. https://doi.org/10.1002/ijc.31176
Chen Y, Sun R, Liu W (2022) Impact of a previous cancer history on the overall survival of patients with primary gastric cancer: a SEER population-based study. Eur J Surg Oncol. https://doi.org/10.1016/j.ejso.2022.06.022
Choudhury A, Nelson LD, Teo MT, Chilka S, Bhattarai S, Johnston CF, Elliott F, Lowery J, Taylor CF, Churchman M, Bentley J, Knowles MA, Harnden P, Bristow RG, Bishop DT, Kiltie AE (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res 70(18):7017–7026. https://doi.org/10.1158/0008-5472.Can-10-1202
Cui Z, Yin Z, Li X, Wu W, Guan P, Zhou B (2012) Association between polymorphisms in XRCC1 gene and clinical outcomes of patients with lung cancer: a meta-analysis. BMC Cancer 12:71. https://doi.org/10.1186/1471-2407-12-71
Dacosta Byfield S, Chen D, Yim YM, Reyes C (2013) Age distribution of patients with advanced non-melanoma skin cancer in the United States. Arch Dermatol Res 305(9):845–850. https://doi.org/10.1007/s00403-013-1357-2
De Ruyck K, Szaumkessel M, De Rudder I, Dehoorne A, Vral A, Claes K, Velghe A, Van Meerbeeck J, Thierens H (2007) Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res 631(2):101–110. https://doi.org/10.1016/j.mrgentox.2007.03.010
Filipovich AH, Mathur A, Kamat D, Shapiro RS (1992) Primary immunodeficiencies: genetic risk factors for lymphoma. Cancer Res 52(19 Suppl):5465s–5467s
Hjalgrim H, Frisch M, Storm HH, Glimelius B, Pedersen JB, Melbye M (2000) Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin’s lymphoma. Int J Cancer 85(5):639–642. https://doi.org/10.1002/(sici)1097-0215(20000301)85:5%3c639::aid-ijc7%3e3.0.co;2-l
Howlader N, N. A., Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2018. Retrieved from Bethesda, MD: https://seer.cancer.gov/csr/1975_2018/
Johannesdottir SA, Lash TL, Jensen A, Farkas DK, Olesen AB (2012) Mortality in cancer patients with a history of cutaneous squamous cell carcinoma–a nationwide population-based cohort study. BMC Cancer 12:126. https://doi.org/10.1186/1471-2407-12-126
Kahn HS, Tatham LM, Patel AV, Thun MJ, Heath CW Jr (1998) Increased cancer mortality following a history of nonmelanoma skin cancer. JAMA 280(10):910–912. https://doi.org/10.1001/jama.280.10.910
Kang SY, Lee KG, Lee W, Shim JY, Ji SI, Chung KW, Chung YK, Kim NK (2007) Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population. Cancer Sci 98(5):716–720. https://doi.org/10.1111/j.1349-7006.2007.00436.x
Karagas MR, Greenberg ER, Mott LA, Baron JA, Ernster VL (1998) Occurrence of other cancers among patients with prior basal cell and squamous cell skin cancer. Cancer Epidemiol Biomarkers Prev 7(2):157–161
Kawashima A, Nakayama M, Kakuta Y, Abe T, Hatano K, Mukai M, Nagahara A, Nakai Y, Oka D, Takayama H, Yoshioka T, Hoshida Y, Itatani H, Nishimura K, Nonomura N (2011) Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer. Clin Cancer Res 17(8):2561–2569. https://doi.org/10.1158/1078-0432.Ccr-10-1963
Kraemer KH, Lee MM, Andrews AD, Lambert WC (1994) The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer The Xeroderma Pigmentosum Paradigm. Arch Dermatol 130(8):1018–1021
Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ (2007) Xeroderma pigmentosum, trichothiodystrophy and cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145(4):1388–1396. https://doi.org/10.1016/j.neuroscience.2006.12.020
Lin Y, Chahal HS, Wu W, Cho HG, Ransohoff KJ, Song F, Tang JY, Sarin KY, Han J (2017) Association study of genetic variation in DNA repair pathway genes and risk of basal cell carcinoma. Int J Cancer 141(5):952–957. https://doi.org/10.1002/ijc.30786
Ming ME, Levy RM, Hoffstad OJ, Filip J, Gimotty PA, Margolis DJ (2004) Validity of patient self-reported history of skin cancer. Arch Dermatol 140(6):730–735. https://doi.org/10.1001/archderm.140.6.730
Morton LM, Turner JJ, Cerhan JR, Linet MS, Treseler PA, Clarke CA, Jack A, Cozen W, Maynadie M, Spinelli JJ, Costantini AS, Rudiger T, Scarpa A, Zheng T, Weisenburger DD (2007) Proposed classification of lymphoid neoplasms for epidemiologic research from the pathology working group of the international lymphoma epidemiology consortium (interlymph). Blood 110(2):695–708. https://doi.org/10.1182/blood-2006-11-051672
Muzic JG, Schmitt AR, Wright AC, Alniemi DT, Zubair AS, Olazagasti Lourido JM, Sosa Seda IM, Weaver AL, Baum CL (2017) Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in Olmsted county, Minnesota, 2000 to 2010. Mayo Clin Proc 92(6):890–898. https://doi.org/10.1016/j.mayocp.2017.02.015
Nietz S, O’Neil DS, Ayeni O, Chen WC, Joffe M, Jacobson JS, Neugut AI, Ruff P, Mapanga W, Buccimazza I, Singh U, Čačala S, Stopforth L, Phakathi B, Chirwa T, Cubasch H (2020) A comparison of complete pathologic response rates following neoadjuvant chemotherapy among South African breast cancer patients with and without concurrent HIV infection. Breast Cancer Res Treat 184(3):861–872. https://doi.org/10.1007/s10549-020-05889-8
Nugent Z, Demers AA, Wiseman MC, Mihalcioiu C, Kliewer EV (2005) Risk of second primary cancer and death following a diagnosis of nonmelanoma skin cancer. Cancer Epidemiol Biomarkers Prev 14(11 Pt 1):2584–2590. https://doi.org/10.1158/1055-9965.Epi-05-0379
Omland SH, Gniadecki R, Haedersdal M, Helweg-Larsen J, Omland LH (2016) Skin cancer risk in hematopoietic stem-cell transplant recipients compared with background population and renal transplant recipients: a population-based cohort study. JAMA Dermatol 152(2):177–183. https://doi.org/10.1001/jamadermatol.2015.3902
Ong EL, Goldacre R, Hoang U, Sinclair R, Goldacre M (2014) Subsequent primary malignancies in patients with nonmelanoma skin cancer in England: a national record-linkage study. Cancer Epidemiol Biomarkers Prev 23(3):490–498. https://doi.org/10.1158/1055-9965.Epi-13-0902
Percy, C., Holten, V. v., Muir, C. S., & Organization, W. H. (1990). International classification of diseases for oncology: World Health Organization.
Rees JR, Zens MS, Gui J, Celaya MO, Riddle BL, Karagas MR (2014) Non melanoma skin cancer and subsequent cancer risk. PLoS ONE 9(6):e99674. https://doi.org/10.1371/journal.pone.0099674
Rendleman J, Antipin Y, Reva B, Adaniel C, Przybylo JA, Dutra-Clarke A, Hansen N, Heguy A, Huberman K, Borsu L (2014) Genetic variation in DNA repair pathways and risk of non-Hodgkin’s lymphoma. PLoS ONE 9(7):e101685
Renzi C, Mastroeni S, Passarelli F, Potenza C, Pasquini P (2011) Reliability of self-reported information on skin cancer among elderly patients with squamous cell carcinoma. Ann Epidemiol 21(7):551–554
Rogers HW, Weinstock MA, Harris AR, Hinckley MR, Feldman SR, Fleischer AB, Coldiron BM (2010) Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 146(3):283–287. https://doi.org/10.1001/archdermatol.2010.19
Rogers HW, Weinstock MA, Feldman SR, Coldiron BM (2015) Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol 151(10):1081–1086. https://doi.org/10.1001/jamadermatol.2015.1187
Rubió-Casadevall J, Hernandez-Pujol AM, Ferreira-Santos MC, Morey-Esteve G, Vilardell L, Osca-Gelis G, Vilar-Coromina N, Marcos-Gragera R (2016) Trends in incidence and survival analysis in non-melanoma skin cancer from 1994 to 2012 in Girona, Spain: a population-based study. Cancer Epidemiol 45:6–10. https://doi.org/10.1016/j.canep.2016.09.001
Ruczinski I, Jorgensen TJ, Shugart YY, Schaad YB, Kessing B, Hoffman-Bolton J, Helzlsouer KJ, Kao WH, Wheless L, Francis L, Alani RM, Strickland PT, Smith MW, Alberg AJ (2012) A population-based study of DNA repair gene variants in relation to non-melanoma skin cancer as a marker of a cancer-prone phenotype. Carcinogenesis 33(9):1692–1698. https://doi.org/10.1093/carcin/bgs170
Small J, Barton V, Peterson B, Alberg AJ (2016) Keratinocyte carcinoma as a marker of a high cancer-risk phenotype. Adv Cancer Res 130:257–291. https://doi.org/10.1016/bs.acr.2016.01.003
Smolarz B, Michalska MM, Samulak D, Romanowicz H, Wójcik L (2019) Polymorphism of DNA repair genes in breast cancer. Oncotarget 10(4):527–535. https://doi.org/10.18632/oncotarget.26568
Song F, Chen ST, Li X, Han J (2018) Personal history of keratinocyte carcinoma is associated with reduced risk of death from invasive melanoma in men. J Am Acad Dermatol 78(5):957–963. https://doi.org/10.1016/j.jaad.2017.12.075
Sørensen HT, Mellemkjaer L, Nielsen GL, Baron JA, Olsen JH, Karagas MR (2004) Skin cancers and non-hodgkin lymphoma among users of systemic glucocorticoids: a population-based cohort study. J Natl Cancer Inst 96(9):709–711. https://doi.org/10.1093/jnci/djh118
Teo MT, Landi D, Taylor CF, Elliott F, Vaslin L, Cox DG, Hall J, Landi S, Bishop DT, Kiltie AE (2012) The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes. Carcinogenesis 33(3):581–586. https://doi.org/10.1093/carcin/bgr300
Toro JR, Blake PW, Björkholm M, Kristinsson SY, Wang Z, Landgren O (2009) Prior history of non-melanoma skin cancer is associated with increased mortality in patients with chronic lymphocytic leukemia. Haematologica 94(10):1460–1464. https://doi.org/10.3324/haematol.2008.004721
Ullrich SE, Kripke ML, Ananthaswamy HN (2002) Mechanisms underlying UV-induced immune suppression: implications for sunscreen design. Exp Dermatol 11(Suppl 1):13–16. https://doi.org/10.1034/j.1600-0625.11.s.1.4.x
Vajdic CM, van Leeuwen MT, Webster AC, McCredie MR, Stewart JH, Chapman JR, Amin J, McDonald SP, Grulich AE (2009) Cutaneous melanoma is related to immune suppression in kidney transplant recipients. Cancer Epidemiol Biomarkers Prev 18(8):2297–2303. https://doi.org/10.1158/1055-9965.Epi-09-0278
Welsh MM, Applebaum KM, Spencer SK, Perry AE, Karagas MR, Nelson HH (2009) CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer. Cancer Res 69(15):6158–6163. https://doi.org/10.1158/0008-5472.Can-09-0415
Wheless L, Kistner-Griffin E, Jorgensen TJ, Ruczinski I, Berthier-Schaad Y, Kessing B, Hoffman-Bolton J, Francis L, Shugart YY, Strickland PT, Kao WH, Alani RM, Smith MW, Alberg AJ (2012) A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer. J Invest Dermatol 132(5):1354–1362. https://doi.org/10.1038/jid.2012.4
Zhou H, Huang Y, Qiu Z, Zhao H, Fang W, Yang Y, Zhao Y, Hou X, Ma Y, Hong S, Zhou T, Zhang Y, Zhang L (2018) Impact of prior cancer history on the overall survival of patients newly diagnosed with cancer: a pan-cancer analysis of the SEER database. Int J Cancer 143(7):1569–1577. https://doi.org/10.1002/ijc.31543
Funding
This work has been supported in part by the Collaborative Data Services Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute and funded in part by Moffitt’s Cancer Center Support Grant (P30-CA076292).
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All authors contributed to the study conception and design. Data were obtained from Moffitt’s Collaborative Data Services Core through KG. Data analysis was performed by YZ. Material preparation was performed by YZ and RA. The first draft of the manuscript was written by RA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Financial interests: Rossybelle P. Amorrortu, Yayi Zhao, Sandy Stewart, Kavita M. Ghia, Dr. Vonetta L. Williams, and Dr. Kenneth Tsai declare they have no financial interests. Dr. Vernon K. Sondak is a compensated consultant for Merck, Novartis, Regeneron, and Iovance. Non-financial interests: Dr. Dana E. Rollison serves on the Board of Directors for NanoString Technologies, Inc. Dr. Vernon K. Sondak serves on the Advisory Boards for BMS, Novartis and Eisai. Dr. Javier Pinilla is a compensated consultant for Janssen, AbbVie, AstraZeneca, Takeda, Novartis, TG Therapeutics, MEI, and BeiGene. Dr. Julio Chavez is a paid consultant for Morphosys, Kite Pharma, Amgen, AbbVie, BeiGene, AstraZeneca, ADC Therapeutics, TG Therapeutics, and Novartis Pharmaceutical Corp.
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The Advarra Institutional Review Board determined that the study was exempt from oversight and met the criteria for and granted a Waiver of HIPPA Authorization. The procedures used in this study adhere to the tenets of the Belmont Report.
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Amorrortu, R.P., Zhao, Y., Stewart, S. et al. History of keratinocyte carcinoma and survival after a second primary malignancy: the Moffitt Cancer Center patient experience. J Cancer Res Clin Oncol 149, 3607–3621 (2023). https://doi.org/10.1007/s00432-022-04210-y
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DOI: https://doi.org/10.1007/s00432-022-04210-y