[Show abstract][Hide abstract] ABSTRACT: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort.
The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed.
Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age.
Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.
British Journal of Cancer 08/2010; 103(4):575-80. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
European journal of cancer (Oxford, England: 1990) 02/2010; 46(6):1041-8. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgery for rectal cancer is associated with high morbidity and mortality rates. The reason for this has been much debated. This population-based study reports the findings on postoperative morbidity and mortality after rectal cancer surgery following the introduction of a centralized colorectal unit in a county central hospital, supervised by a colorectal surgeon using the most recent techniques.
All consecutive patients with rectal cancer who underwent surgery at four county hospitals in the Västmanland county in Sweden during 1993-1996 (n = 133) were compared with patients who underwent surgery at the new colorectal unit in the county central hospital from 1996 to 1999 (n = 144).
The number of operating surgeons was reduced from 26 to four. The postoperative mortality rate decreased from 8 to 1 per cent (P = 0.002) and the total postoperative complication rate was reduced from 57 to 24 per cent (P < 0.001). Surgical complications dropped from 37 to 11 per cent (P < 0.001). The relaparotomy rate fell from 11 to 4 per cent (P < 0.05). Postoperative stay in hospital was reduced from a median of 13 to 9 days (P < 0.001).
The new organization, with centralized rectal cancer surgery using modern techniques, reduced postoperative mortality and overall morbidity rates to less than half.
British Journal of Surgery 02/2001; 88(2):273-7. · 5.21 Impact Factor