Volume 8 Supplement 1

Proceedings of the 13th Annual Meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer

Open Access

Characteristics of Lynch syndrome in 13 Hispanic Families

  • Charite Ricker1Email author,
  • Nancy Klipfel1,
  • Glenn Ault1,
  • Lynda Roman1,
  • Darcy Spicer1 and
  • Heinz-Josef Lenz1
Hereditary Cancer in Clinical Practice20108(Suppl 1):P19

DOI: 10.1186/1897-4287-8-S1-P19

Published: 25 May 2010

Background

While the incidence of colorectal cancer is lower in Hispanics than in non-Hispanic Caucasians, it is the second most common cancer in this diverse ethnic population. Emerging data indicate hereditary colon cancer syndromes contribute to cancer burden regardless of race and ethnicity. These data derive from research and cohorts where Hispanics are underrepresented. Here we report on 14 individuals from 13 Hispanic families with Lynch syndrome.

Methods

After referral for cancer risk assessment, immunohistochemical staining was performed for the four MMR gene products and/or analysis of the appropriate gene(s) was initiated.

Results

Clinical features of the 14 individuals identified with Lynch syndrome are detailed below (Table 1). Of the 13 families, 9 (71 %) are from Mexico, 4 from Central America. Seventy-two percent presented first with colon cancer (64% right-sided); 14% presented first with gastric cancer; and 1 individual with uterine cancer. The average age at first cancer diagnosis was 38.6 years; 38.5 years for colon cancer. One third had two primaries, 3 synchronous. Five of the 13 families met Amsterdam I or II criteria, while 8 met Bethesda guidelines. Two were single-case indicators, two had multiple family members affected in only One generation, and the remainder had contributory family history but too distant to meet Amsterdam. Twelve individuals underwent genetic testing; 8 MLH1 mutations and 3 MSH2 mutations were detected. Pathology was thoroughly reviewed in 11 colon tumors; 2 were well differentiated, 6 were well to moderately differentiated and 3 were focally poorly differentiated, 3 exhibited tumor infiltrating lymphocytes, 3 showed Crohn's reaction, 9 demonstrated pushing borders, 3 contained dirty necrosis, and 4 were mucinous carcinoma (>50%) with an additional 4 cases showing mucinous features (<50%).

Table 1

 

Country of Origin**

1st Cancer Diagnosis

2nd Cancer Diagnosis

Family History Classification

IHC-Proteins unexpressed

Gene Analysis

   

Age

 

Age

  

Gene

 

1

ES

Cecal

37

Transverse

37

Amsterdam I

hMLH1/hPMS2

MLH1

S698X

2

GU

Sigmoid

34

  

Amsterdam I

hMSH2/hMSH6

MSH2

S142X

3

MX

Sigmoid

33

  

Amsterdam I

 

MLH1

1105insT+

4

MX

Gastric

31

Rectal

32

Amsterdam I

 

MLH1

R226X

5

MX

Uterine

48

  

Amsterdam II

hMLH1/hPMS2

MLH1

Q409X

6

MX

Cecal

47

Descendng

47

Bethesda

hMLH1/hPMS2

Declined

 

7

GU

Cecal

45

  

Bethesda

hMLH1/hPMS2

MLH1

ICS3-2A>G+

8

MX

Sigmoid

40

  

Bethesda

hMHS2/hMSH6

None detected1

 

9

MX

Cecal

36

  

Bethesda

hMSH2/hMSH6

MSH2

Q593X

10

ES

Cecal

31

  

Bethesda

hMLH1/hPMS2

MLH1

K618del

11

MX

Transverse

45

RCC-clear cell

45

Bethesda

hMLH1/hPMS2

MLH1

del exon 2-3

12

MX

Splenic Flexure

32

  

Bethesda

Pending

MSH2

2179delCinsAG+

13*

MX

Cecal

44

  

Bethesda

hMSH2/hMSH6

MSH2

Q76X

14*

MX

Gastric

37

Cecal

47

Bethesda

hMSH2/hMSH6

Declined

 

*Individuals 13 and 14 are brothers; **MX=Mexico; ES=El Salvador; GU=Guatemala

1MLH1 and MSH6 sequencing (MSH6 VUS 4071ins4), MSH2/MLH1 rearrangement studies

+not reported in Leiden Variation Open Database or the Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff

Conclusions

As the U.S. Hispanic population grows and access to cancer genetics services increases, the contribution of Lynch syndrome must be understood. In our cohort of Hispanic families, the early-onset right-sided colon cancer is consistent with known Lynch syndrome features. Of interest are the young age at diagnosis and the high number of families meeting only Bethesda criteria. Another area to explore is the frequency of gastric cancer in Hispanic families with Lynch syndrome, given the higher incidence of gastric cancer in Latin America.

Declarations

Acknowledgement

Funded by the USC Norris Foundation

Authors’ Affiliations

(1)
University of Southern California (USC)

Copyright

© Ricker et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

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