globally , colorectal cancer ( crc ) is the fourth most common cancer in men and the third most common cancer in women1 ) .
although most crc occurs sporadically , genetic predisposition related to its pathogenesis has been reported2 ) .
one of the most investigated genotypic subtypes of crc is the aberrancy of the mismatch repair pathway , usually found in combination with microsatellite instability ( msi)3 ) .
lynch syndrome , also called hereditary nonpolypsosis colorectal cancer ( hnpcc ) , is caused by germline mutation of mismatch repair ( mmr ) genes4 ) .
individuals affected by lynch syndrome by heterozygous mutation of mmr usually present crc in the fourth or fifth decade ; however .
k - ras , a critical oncogene and its product playing a key role in the kinase signaling growth pathway , plays a critical role in the pathogenesis of crc6 ) .
the revised bethesda guidelines recommendations were established for a better understanding and identifying individuals with hnpcc ; however , diagnosis of hnpcc at a young age , less than second decades , is difficult as clinician does not suspect it due to its rarity .
we recently cared for a female patient with lynch syndrome , carrying heterozygous mlh1 germline mutation and k - ras missense somatic mutation ; she had crc at a very early age , 13-years old , and congenital heart disease ( transposition of great arteries ) .
a 13-year - old korean female was born without complications . soon after delivery , she was diagnosed with transposition of great arteries and corrective surgery was performed at 3 months of age .
she grew up without any specific health problem until she reached 12 years of age . at 13 years of age
she visited the hospital for weight loss of 10 kg over 2 months and a pale appearance .
she was diagnosed as having helicobacter pylori gastritis by endoscopy and referred to our hospital for further h. pylori eradication and iron supplementation for management of iron deficiency anemia ( hemoglobin , 7.1 g / dl ; serum iron , 13 g / dl ; total iron - binding capacity , 381 g / dl ; ferritin , 6.50 ng / dl ) .
she did not have any skin lesions such as caf - au - lait spots and physical finding was not remarkable .
after treatment , she was free from h. pylori gastritis ; however , despite taking a sufficient iron supplement for 1 month , iron deficiency persisted without improvement and palpable mass was noticed . for further evaluation of resistant anemia and palpable abdominal mass , colonoscopy was performed and revealed a huge irregular multilobular mass located on the rectum approximately 6 cm from the anal verge .
biopsy was performed at that site and revealed adenocarcinoma of the rectum . computed tomography of the abdomen , pelvis , and chest showed a polypoid mass ( 2.6 cm2.5 cm ) in the rectum and a huge mass ( 6.7 cm5.1 cm ) in the transverse colon and ascending colon with lymph node enlargement .
total proctocolectomy with ileal pouch anal anastomosis was performed and stage of cancer was t4n2m0 .
1 ) . genetic study of the pathologic specimen revealed a k - ras gene mutation at codon 12 as gly12asp ( c. 35g > a ) and msi was found in cancer cells by polymerase chain reaction amplification and fragment analysis by gene analyzer .
germline mutation study of mmr genes using patient 's blood revealed a splicing mutation at mlh1 as c. 678 - 1g > c while other findings were unremarkable ( fig .
2 ) . genetic study of her parents was performed and revealed that mother had a same mlh1 mutation of patient ; however father had none .
in addition , 2 cases of crc were detected on her maternal relatives ( fig .
3 ) . after informed consent was obtained , 12 cycles of chemotherapy consisting of oxaliplatin ( 85 mg / m on day 1 ) , leucovorin ( 200 mg / m on days 1 , 2 ) , and 5-fluorouracil ( 1,500 mg /
m on days 1 , 2 ) ( folfox ) were completed without any specific problems , with the exception of myelosuppression .
diagnostic work - up for recurrence was followed and a suspicious recurrent lesion was noticed at the duodenal second portion and pancreas head portion after completion of the eighth cycle of chemotherapy .
after completion of 12 cycles of chemotherapy , imaging study revealed increased mass at the duodenal portion .
nonetheless , some cancers arise as the consequence of inherited genetic mutations ( germline mutations ) . lynch syndrome , caused by germline mutation of mmr genes , such as mlh1 , msh2 , msh6 , and pms2 , is an inherited cancer syndrome789 ) . lynch syndrome - related tumors , such as crc and endometrium tumor in females , and a tumor spectrum comprised of hematological malignancies ,
development of crc by heterozygous mutation of mmr usually occurs during the fourth or fifth decade .
however , in recent years , early onset of crc has been reported in children with either compound heterozygosity or homozygosity for the mmr gene defect101112 ) . in our case crc by heterozygous germline mutation of mmr gene and a point somatic mutation of the k - ras developed in teenage without compound heterozygosity or homozygosity for the mmr gene defect .
somatic mutation of k - ras gene , mainly missense mutation at codons 12 and 13 , is found less frequently in crc with lynch syndrome than sporadic crc13 ) .
the effect of k - ras gene mutation on the time of occurrence and prognosis of crc is uncertain14 ) .
however , it could be considered that the mutation on the growth factor signaling pathway ( k - ras ) and mmr gene mutation could contribute synergistically to occurrence of crc at a very early age .
some studies have also shown that age at diagnosis of crc decreases in successive generations of lynch families15 ) .
early diagnosis and management of crc in teenagers with lynch syndrome is difficult , since occurrence of crc is very unusual in this period . in our case ,
diagnosis was delayed and crc was managed improperly . the necessity of early screening for detection of crc in subjects with a family history of early onset crc , even before two decades , should be emphasized .
 lynch syndrome is the most common inherited colon cancer syndrome . 
 patients with lynch syndrome develop a range of cancers including colorectal cancer ( crc ) and carry a mutation on one of the mismatched repair ( mmr ) genes . 
 although crc usually occurs after the fourth decade in patients with lynch syndrome harboring a heterozygous mmr gene mutation , it can occur in children with lynch syndrome who have a compound heterozygous or homozygous mmr gene mutation . 
 we report a case of crc in a 13-year - old patient with lynch syndrome and congenital heart disease . this patient had a heterozygous mutation in mlh1 ( an mmr gene ) , but 
 no compound mmr gene defects , and a k - ras somatic mutation in the cancer cells . 
Introduction
Case report
Discussion