Nicholas L Berlin1, Brenda Cartmel2, David J Leffell3, Allen E Bale3, Susan T Mayne2, Leah M Ferrucci4. 1. Yale School of Public Health, New Haven, CT 06520, United States. 2. Yale School of Public Health, New Haven, CT 06520, United States; Yale Cancer Center, New Haven, CT 06520, United States. 3. Yale Cancer Center, New Haven, CT 06520, United States; Yale University School of Medicine, New Haven, CT 06520, United States. 4. Yale School of Public Health, New Haven, CT 06520, United States; Yale Cancer Center, New Haven, CT 06520, United States. Electronic address: leah.ferrucci@yale.edu.
Abstract
BACKGROUND: As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). MATERIALS AND METHODS: Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. RESULTS: A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). CONCLUSIONS: Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC.
BACKGROUND: As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). MATERIALS AND METHODS: Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. RESULTS: A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). CONCLUSIONS: Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC.
Authors: Fatima Birch-Johansen; Allan Jensen; Lone Mortensen; Anne Braae Olesen; Susanne K Kjær Journal: Int J Cancer Date: 2010-11-01 Impact factor: 7.396
Authors: Rodolfo Valdez; Paula W Yoon; Nadeem Qureshi; Ridgely Fisk Green; Muin J Khoury Journal: Annu Rev Public Health Date: 2010 Impact factor: 21.981
Authors: Simon N Stacey; Daniel F Gudbjartsson; Patrick Sulem; Jon T Bergthorsson; Rajiv Kumar; Gudmar Thorleifsson; Asgeir Sigurdsson; Margret Jakobsdottir; Bardur Sigurgeirsson; Kristrun R Benediktsdottir; Kristin Thorisdottir; Rafn Ragnarsson; Dominique Scherer; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Veronica Höiom; Rafael Botella-Estrada; Virtudes Soriano; Pablo Juberías; Matilde Grasa; Francisco J Carapeto; Pilar Tabuenca; Yolanda Gilaberte; Julius Gudmundsson; Steinunn Thorlacius; Agnar Helgason; Theodora Thorlacius; Aslaug Jonasdottir; Thorarinn Blondal; Sigurjon A Gudjonsson; Gudbjörn F Jonsson; Jona Saemundsdottir; Kristleifur Kristjansson; Gyda Bjornsdottir; Steinunn G Sveinsdottir; Magali Mouy; Frank Geller; Eduardo Nagore; José I Mayordomo; Johan Hansson; Thorunn Rafnar; Augustine Kong; Jon H Olafsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2008-10-12 Impact factor: 38.330
Authors: Hongmei Nan; Mousheng Xu; Peter Kraft; Abrar A Qureshi; Constance Chen; Qun Guo; Frank B Hu; Gary Curhan; Christopher I Amos; Li-E Wang; Jeffrey E Lee; Qingyi Wei; David J Hunter; Jiali Han Journal: Hum Mol Genet Date: 2011-06-23 Impact factor: 6.150
Authors: Sophie C Flohil; Esther de Vries; H A Martino Neumann; Jan-Willem W Coebergh; Tamar Nijsten Journal: Acta Derm Venereol Date: 2011-01 Impact factor: 4.437
Authors: Simon N Stacey; Patrick Sulem; Gisli Masson; Sigurjon A Gudjonsson; Gudmar Thorleifsson; Margret Jakobsdottir; Asgeir Sigurdsson; Daniel F Gudbjartsson; Bardur Sigurgeirsson; Kristrun R Benediktsdottir; Kristin Thorisdottir; Rafn Ragnarsson; Dominique Scherer; Kari Hemminki; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Rafael Botella-Estrada; Virtudes Soriano; Pablo Juberias; Berta Saez; Yolanda Gilaberte; Victoria Fuentelsaz; Cristina Corredera; Matilde Grasa; Veronica Höiom; Annika Lindblom; Johannes J Bonenkamp; Michelle M van Rossum; Katja K H Aben; Esther de Vries; Mario Santinami; Maria G Di Mauro; Andrea Maurichi; Judith Wendt; Pia Hochleitner; Hubert Pehamberger; Julius Gudmundsson; Droplaug N Magnusdottir; Solveig Gretarsdottir; Hilma Holm; Valgerdur Steinthorsdottir; Michael L Frigge; Thorarinn Blondal; Jona Saemundsdottir; Hjördis Bjarnason; Kristleifur Kristjansson; Gyda Bjornsdottir; Ichiro Okamoto; Licia Rivoltini; Monica Rodolfo; Lambertus A Kiemeney; Johan Hansson; Eduardo Nagore; José I Mayordomo; Rajiv Kumar; Margaret R Karagas; Heather H Nelson; Jeffrey R Gulcher; Thorunn Rafnar; Unnur Thorsteinsdottir; Jon H Olafsson; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2009-07-05 Impact factor: 38.330
Authors: Leah M Ferrucci; Brenda Cartmel; Annette M Molinaro; Patricia B Gordon; David J Leffell; Allen E Bale; Susan T Mayne Journal: J Invest Dermatol Date: 2011-12-08 Impact factor: 8.551
Authors: Lee Wheless; Emily Kistner-Griffin; Timothy J Jorgensen; Ingo Ruczinski; Yvette Berthier-Schaad; Bailey Kessing; Judith Hoffman-Bolton; Lesley Francis; Yin Yao Shugart; Paul T Strickland; W H Linda Kao; Rhoda M Alani; Michael W Smith; Anthony J Alberg Journal: J Invest Dermatol Date: 2012-02-16 Impact factor: 8.551
Authors: Jae H Kang; Trang VoPham; Francine Laden; Bernard A Rosner; Barbara Wirostko; Robert Ritch; Janey L Wiggs; Abrar Qureshi; Hongmei Nan; Louis R Pasquale Journal: J Glaucoma Date: 2020-06 Impact factor: 2.503