The Impact of Race or Ethnicity The Impact of Race or Ethnicity in Crohn's Disease in Crohn's Disease

Edward V. Loftus, Jr., M.D.Professor of Medicine

Mayo ClinicRochester, Minnesota, USA

Race & Ethnicity in IBD Race & Ethnicity in IBD –– Historical ViewHistorical View

• Caucasians, especially northern European ancestry– Scandinavia– Northern Europe– British Isles– United States and Canada

• Increased risk in Jews• Uncommon in African Americans and other

racial minorities in U.S.

Risk of CrohnRisk of Crohn’’s Disease Among Jews:s Disease Among Jews:PopulationPopulation--Based Estimate in WalesBased Estimate in Wales

0

50

100

150

200

250

300

Non-Jewish Jewish

Prev

alen

ce (p

er 1

00,0

00)

Mayberry et al: Digestion 1986

Trends in Prevalence of CrohnTrends in Prevalence of Crohn’’s s Disease in Tel Aviv 1970Disease in Tel Aviv 1970--8080

0

5

10

15

20

25

30

1970 1980

Adj

uste

d Pr

eval

ence

(per

100

,000

PYR

)

Europe-AmericaIsraelAsia-Africa

Fireman et al: Am J Gastroenterol 1989

Trends in Incidence of CrohnTrends in Incidence of Crohn’’s s Disease By Race: BaltimoreDisease By Race: Baltimore

0

1

2

3

4

5

1960-63 1973 1977-79

Calendar Year

Adj

uste

d In

cide

nce

(per

100

,000

PY

R)

WhiteMaleWhiteFemaleNonwhiteMaleNonwhiteFemale

Calkins et al: Dig Dis Sci 1984

Racial/Ethnic Variation in CrohnRacial/Ethnic Variation in Crohn’’s s Prevalence: Southern California 1984Prevalence: Southern California 1984--8888

05

101520253035404550

White African-American

Hispanic Asian Other

Pre

vale

nce

(per

100

,000

)

Kurata et al: Gastroenterology 1992

Shifting Paradigms?Shifting Paradigms?

• More common in African-Americans• More common in those of Hispanic ancestry• More common in Asians

– Native Asians (East, South)– South Asian migrants

Geographical Prevalence of IBDGeographical Prevalence of IBDGeographical Prevalence of IBD

HighHighHighIntermediateIntermediateIntermediateLowLowLow CP1169260-5

0

2

4

6

8

10

12

1955 1960 1965 1970 1975 1980 1985 1990 1995Year

Inci

denc

e/10

0,00

0 PY

R

Olmsted County, MN

Cardiff, Wales

Rochester, New York

Iceland

Aberdeen, Scotland

Helsinki, Finland

Florence, Italy

Temporal Trends in Incidence of CrohnTemporal Trends in Incidence of Crohn’’s s Disease in Europe and North America, 1955Disease in Europe and North America, 1955--9595

Loftus EV. Gastroenterology 2004

IBD Among AfricanIBD Among African--American American Children in Georgia, USAChildren in Georgia, USA

• Study of pediatric IBD patients evaluated at Emory 1986-95

• Incidence of Crohn’s rose from 7 to 12 per 100,000 over the study period

• Incidence of UC remained stable at 5 – 7 over the study period

• Rates were broadly similar to those of whites

Ogunbi S, et al. J Pediatr 1998;133:103-7.

Racial/Ethnic Minorities with IBD Racial/Ethnic Minorities with IBD -- TexasTexas

• Mexican-Americans more likely to get UC than Crohn’s– More proximal disease extent– Fewer extraintestinal manifestations– High prevalence of pANCA (100%)

• African-Americans more likely to have Crohn’s– More colonic or perianal, less ileal– More arthritis and uveitis

Basu D et al. Am J Gastroenterol 2005;100:2254-61.

Racial/Ethnic Minorities with Racial/Ethnic Minorities with CrohnCrohn’’s s –– Six CentersSix Centers

• African Americans (n = 127)– Upper gut Crohn’s: OR, 2.8 (1.4-5.5)*– Colonic disease: OR, 1.9 (1.1-3.4)– Perianal disease: OR, 1.7 (1.03-2.8)– More extraintestinal

• Hispanics (n = 169)– Perianal disease: OR 2.9 (1.8-4.6)*– Erythema nodosum: OR 3.3 (1.7-6.4)

* controls = 830 non-Hispanic whitesNguyen GC et al. Am J Gastroenterol 206;101;1012-23.

Does Race Influence Behavior Does Race Influence Behavior or Severity of Crohnor Severity of Crohn’’s? s?

• Comparison between 55 African Americans and 155 whites with Crohn’s at Univ of Maryland

• African Americans more likely to have colonic and/or perianal disease

• No differences in perforating behavior, need for surgery, and prevalence of EIMs

Cross RK et al. Inflamm Bowel Dis 2007;12:192-8.

Ethnic Variation of IBD in CanadaEthnic Variation of IBD in Canada

• Highest IBD incidence rates in suburban Winnepeg, lowest rates in northern province and urban core (more First Peoples*)

• Incidence and prevalence of Crohn’s is lowest in British Columbia, which has the highest prevalence of visible minorities

* Aboriginal Canadians (aka Native Americans)

Green C et al. Am J Epidemiol 2006;164:615-23.Bernstein CN et al. Am J Gastroenterol 2006;101:1559-68.

Ulcerative Colitis in Punjab, IndiaUlcerative Colitis in Punjab, India

• Province of northern India– 20 million people in 1991– 2/3 Sikh, 1/3 Hindu

• Survey of randomly selected districts by multidisciplinary team for diarrhea or rectal bleeding– If yes, stool studies and sigmoidoscopy

• Same areas re-surveyed the following year• Prevalence 44.3, incidence 6.0

Sood A, et al. Gut 2003;52:1587-90.

Incidence of IBD Among South Asians and Incidence of IBD Among South Asians and Native Britons in Leicestershire, 1981Native Britons in Leicestershire, 1981--8989

02468

1012141618

Europeans SouthAsiansTotal

Hindu Sikh MuslimAdj

uste

d in

cide

nce

(per

100

,000

PYR

)

CUCCD

Probert et al, Gut 1992;33:687Jayanthi et al, QJMed 1992;82:125

Period Prevalence of IBD Period Prevalence of IBD in Singapore, 1985in Singapore, 1985--9696

02468

1012141618

Chinese Malay Indian

Prev

alen

ce (p

er 1

00,0

00 P

YR)

CUCCD

Lee et al, J Gastroenterol Hepatol 2000;15:622

Prevalence of CARD15 Mutations Prevalence of CARD15 Mutations Among Pediatric CrohnAmong Pediatric Crohn’’ss

0

5

10

15

20

25

30

R702W G908R 302OinsC Any CARD15

Afr Amer n=58Hispanic n=18White n=164

Kugathasasan S et al. Inflamm Bowel Dis 2005;11:631-8.

Are Ethnic Variations Independent of Genetic Variations? Are Ethnic Variations Independent of Genetic Variations? Risk Factors Among 232 Manitobans with CrohnRisk Factors Among 232 Manitobans with Crohn’’s Diseases Disease

Factor OR (95% CI)CARD15 hetero 3.7CARD15 comp het/homo 40.0Jewish ethnicity 18.5Family history Crohn’s 6.2Current smoking 3.0

Multivariate analysis

Bernstein CN et al. Am J Gastroenterol 2007;102:313-23.

Genetics CanGenetics Can’’t Explain It Allt Explain It All

• Prevalence of NOD2/CARD15 mutations varies widely in populations– Low in Scandinavia, Finland, Australia, Celtic

regions– High in Belgium, Canada– Doesn’t correlate tightly with Crohn’s incidence

rates• Don’t forget the twin studies!!!

– 20-50% concordance in identical twins

Kavanaugh J. World J Gastroenterol 2006;12:3673-7.Arnott ID et al. Genes Immun 2004;5:417-25.

ConclusionsConclusions

• Incidence and prevalence of IBD still rising in many areas

• Jews have increased risk relative to non-Jewish Caucasians

• Prevalence of IBD in African-Americans is at least 2/3 that of Caucasian population, perhaps higher

• Higher prevalence of colonic and perianal Crohn’s among African Americans, but no clear difference in behavior or need for surgery

ConclusionsConclusions

• Prevalence among Hispanics rising, but difficult to quantify

• Crohn’s is now being reported in ‘new’ areas such as East Asia, South Asia, and among migrants from South Asia

• Not clear if genetics can completely explain ethnic/racial differences in Crohn’s incidence and phenotype