CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations

Robert R Mc Williams, Eric D Wieben, Kari G. Chaffee, Samuel Antwi, Leon Raskin, Olufunmilayo I. Olopade, Donghui Li, W Edward Jr. Highsmith, Gerardo Colon-Otero, Lauren G. Khanna, Jennifer B. Permuth, Janet E Olson, Harold Frucht, Jeanine Genkinger, Wei Zheng, William J. Blot, Lang Wu, Luciana L. Almada, Martin E Fernandez-Zapico, Hugues SicotteKatrina S. Pedersen, Gloria M Petersen

Research output: Contribution to journalArticle

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Abstract

Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects. Methods: We sequenced CDKN2A in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258-278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5-7.1; P = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0% (OR, 13.4;95%CI, 4.9-36.7; P < 0.001) compared with NHW cases (0.4%). Conclusions: CDKN2A RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs. Impact: RCVs in CDKN2A are frequent in AAs and are associated with risk for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1364-1370
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2018

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Pancreatic Neoplasms
African Americans
Population
Odds Ratio
Confidence Intervals
Minority Groups
North American Indians
Germ-Line Mutation
Tumor Suppressor Genes
Hispanic Americans

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations. / Mc Williams, Robert R; Wieben, Eric D; Chaffee, Kari G.; Antwi, Samuel; Raskin, Leon; Olopade, Olufunmilayo I.; Li, Donghui; Highsmith, W Edward Jr.; Colon-Otero, Gerardo; Khanna, Lauren G.; Permuth, Jennifer B.; Olson, Janet E; Frucht, Harold; Genkinger, Jeanine; Zheng, Wei; Blot, William J.; Wu, Lang; Almada, Luciana L.; Fernandez-Zapico, Martin E; Sicotte, Hugues; Pedersen, Katrina S.; Petersen, Gloria M.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 27, No. 11, 01.11.2018, p. 1364-1370.

Research output: Contribution to journalArticle

Mc Williams, RR, Wieben, ED, Chaffee, KG, Antwi, S, Raskin, L, Olopade, OI, Li, D, Highsmith, WEJ, Colon-Otero, G, Khanna, LG, Permuth, JB, Olson, JE, Frucht, H, Genkinger, J, Zheng, W, Blot, WJ, Wu, L, Almada, LL, Fernandez-Zapico, ME, Sicotte, H, Pedersen, KS & Petersen, GM 2018, 'CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations', Cancer Epidemiology Biomarkers and Prevention, vol. 27, no. 11, pp. 1364-1370. https://doi.org/10.1158/1055-9965.EPI-17-1065
Mc Williams, Robert R ; Wieben, Eric D ; Chaffee, Kari G. ; Antwi, Samuel ; Raskin, Leon ; Olopade, Olufunmilayo I. ; Li, Donghui ; Highsmith, W Edward Jr. ; Colon-Otero, Gerardo ; Khanna, Lauren G. ; Permuth, Jennifer B. ; Olson, Janet E ; Frucht, Harold ; Genkinger, Jeanine ; Zheng, Wei ; Blot, William J. ; Wu, Lang ; Almada, Luciana L. ; Fernandez-Zapico, Martin E ; Sicotte, Hugues ; Pedersen, Katrina S. ; Petersen, Gloria M. / CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations. In: Cancer Epidemiology Biomarkers and Prevention. 2018 ; Vol. 27, No. 11. pp. 1364-1370.
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abstract = "Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects. Methods: We sequenced CDKN2A in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95{\%} confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258-278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95{\%} CI, 1.5-7.1; P = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0{\%} (OR, 13.4;95{\%}CI, 4.9-36.7; P < 0.001) compared with NHW cases (0.4{\%}). Conclusions: CDKN2A RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs. Impact: RCVs in CDKN2A are frequent in AAs and are associated with risk for pancreatic cancer.",
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T1 - CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations

AU - Mc Williams, Robert R

AU - Wieben, Eric D

AU - Chaffee, Kari G.

AU - Antwi, Samuel

AU - Raskin, Leon

AU - Olopade, Olufunmilayo I.

AU - Li, Donghui

AU - Highsmith, W Edward Jr.

AU - Colon-Otero, Gerardo

AU - Khanna, Lauren G.

AU - Permuth, Jennifer B.

AU - Olson, Janet E

AU - Frucht, Harold

AU - Genkinger, Jeanine

AU - Zheng, Wei

AU - Blot, William J.

AU - Wu, Lang

AU - Almada, Luciana L.

AU - Fernandez-Zapico, Martin E

AU - Sicotte, Hugues

AU - Pedersen, Katrina S.

AU - Petersen, Gloria M

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects. Methods: We sequenced CDKN2A in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258-278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5-7.1; P = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0% (OR, 13.4;95%CI, 4.9-36.7; P < 0.001) compared with NHW cases (0.4%). Conclusions: CDKN2A RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs. Impact: RCVs in CDKN2A are frequent in AAs and are associated with risk for pancreatic cancer.

AB - Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects. Methods: We sequenced CDKN2A in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258-278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5-7.1; P = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0% (OR, 13.4;95%CI, 4.9-36.7; P < 0.001) compared with NHW cases (0.4%). Conclusions: CDKN2A RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs. Impact: RCVs in CDKN2A are frequent in AAs and are associated with risk for pancreatic cancer.

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