Background. Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival. Methods. Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals. Results. Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of rectal carcinoma patients received appropriate therapy as opposed to 65% of colon cancers. On multivariable analysis, appropriate reception of therapy (PR 4.99; 95% CI, 1.21–20.6) and signet ring morphology (PR 2.40; 95% CI, 1.33–4.32) were significantly associated with rectal cancers as opposed to colon cancer. Kaplan-Meier analysis revealed a trend towards inferior survival for rectal carcinoma 2 years after diagnosis. Conclusion.A high prevalence of early onset CRC was noted in the study. A trend towards inferior survival was seen in patients with rectal cancer. This finding raises the possibility of rectal carcinoma being an aggressive subset of young CRC.

The majority of patients with the autosomal dominant disorder familial hypercholesterolemia (FH) carry novel mutations in the low density lipoprotein receptor (LDLR) that is involved in cholesterol regulation. In different populations the spectrum of mutations identified is quite different and to date there have been only a few reports of the spectrum of mutations in FH patients from Pakistan. In order to identify the causative LDLR variants the gene was sequenced in a Pakistani FH family, while high resolution melting analysis followed by sequencing was performed in a panel of 27 unrelated sporadic hypercholesterolemia patients. In the family a novel missense variant (c.1916T > G, p.(V639G)) in exon 13 of LDLR was identified in the proband. The segregation of the identified nucleotide change in the family and carrier status screening in a group of 100 healthy subjects was done using restriction fragment length polymorphism analysis. All affected members of the FH family carried the variant and none of the non-affected members nor any of the healthy subjects. In one of the sporadic cases, two sequence changes were detected in exon 9, one of these was a recurrent missense variant (c.1211C > T; p.T404I), while the other was a novel substitution mutation (c.1214 A > C; N405T). In order to define the allelic status of this double heterozygous individual, PCR amplified fragments were cloned and sequenced, which identified that both changes occurred on the same allele. In silico tools (PolyPhen and SIFT) were used to predict the effect of the variants on the protein structure, which predicted both of these variants to have deleterious effect. These findings support the view that there will be a novel spectrum of mutations causing FH in patients with hypercholesterolaemia from Pakistan.

e14680 Background: Early onset colorectal carcinoma (CRC), defined as CRC at age below 45 years is rare. However, an increasing incidence has been noted in Southeast Asia. It is hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and a worse survival. Data on this subject is scarce from this part of the world and hence our objective was to study the clinical presentation and outcome of early onset sporadic CRC in patients at a single tertiary care center in Pakistan. Methods: Data was collected by a retrospective chart review. 131 patients were found eligible for the period between January 1, 2004 and December 31, 2011. A pre-designed and coded questionnaire was used and analysis was done using SPSS. Cox proportional hazard model was used to compute prevalence ratios. Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. Colon and rectal cancers accounted for 55% and 45% of patients respectively. The median age was 35 years (range 16-45 years) and the male to female ratio was 2:1. 74% of patients presented with advanced stage disease [stages III (45%) and IV (29%)]. On comparison, bleeding per rectum, signet ring morphology, stage and grade of tumor were found to be statistically significant for the rectal cancer group on a univariate analysis. 93% of rectal carcinoma patients received appropriate surgery and/or neoadjuvant/adjuvant therapy as opposed to 69% of colon cancers. Median survival was 19 months (range 0-112.5 months). However, Kaplan-Meier analysis revealed a trend towards an inferior survival for rectal carcinoma 2 years after initial diagnosis (p=0.56). Conclusions: Higher incidence of early onset CRC is noted in our population as compared to the western literature. Rectal carcinoma accounts for almost half the patients in this young CRC population. This group was found to have a higher frequency of poor prognostic factors. However, we have noted a similar 2 year survival between the 2 groups, with a trend towards an inferior prognosis with longer followup. It is possible that a larger sample size may have elucidated a statistically significant difference between the two groups.

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