the impact of race or ethnicity in crohn's...
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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