Screening Practices of Unaffected People at Familial Risk of Colorectal Cancer

Our objective was to determine screening practices of unaffected people in the general population at moderately increased and potentially high risk of colorectal cancer (CRC) because of their family history of the disease. A total of 1,627 participants in the Australasian Colorectal Cancer Family Registry study were classified into two CRC risk categories, according to the strength of their family history of the disease. We calculated the proportion of participants that adhered to national CRC screening guidelines by age group and for each familial risk category. We carried out a multinomial logistic regression analysis to evaluate the associations between screening and sociodemographic factors. Of the 1,236 participants at moderately increased risk of CRC, 70 (6%) reported having undergone guideline-defined "appropriate" screening, 251 (20%) reported some, but less than appropriate screening, and 915 (74%) reported never having had any CRC screening test. Of the 392 participants at potentially high risk of CRC, three (1%) reported appropriate screening, 140 (36%) reported some, but less than appropriate screening, and 249 (64%) reported never having had any CRC screening test. On average, those of middle age, higher education, and who had resided in Australia longer were more likely to have had screening for CRC. The uptake of recommended screening by unaffected people at the highest familial risk of developing CRC is extremely low. Guidelines for CRC screening are not being implemented in the population. More research is needed to identify the reasons so as to enable development of strategies to improve participation in screening

Screening practices of Australian men and women categorized as "at or slightly above average risk" of colorectal cancer

PURPOSE: Australia has one of the highest incidences of colorectal cancer (CRC) in the world. In 2006, the federal government introduced a screening program consisting of a one-off fecal occult blood test offered to people turning 50, 55, or 65 years. We conducted a population-based study to estimate CRC screening practices existing outside the current program. METHODS: A total of 1887 unaffected subjects categorized "at or slightly above average risk" of CRC were selected from the Australasian Colorectal Cancer Family Registry. We calculated the proportions of participants that reported appropriate, under- and over-screening according to national guidelines. We performed a logistic regression analysis to evaluate associations between over-screening and a set of socio-demographic factors. RESULTS: Of 532 participants at average risk of CRC, eligible for screening, 4 (0.75 %) reported appropriate screening, 479 (90 %) reported never having been screened, 18 (3 %) reported some but less than appropriate screening, and 31 (6 %) reported over-screening. Of 412 participants aged 50 years or over, slightly above average risk of CRC, 1 participant (0.25 %) reported appropriate screening, 316 (77 %) reported no screening, and 11 (3 %) reported some but less than appropriate screening. Among participants under age 50 years, 2 % of those at average risk and 10 % of those slightly above average risk reported over-screening. Middle-aged people, those with a family history of CRC and those with a university degree, were more likely to be over-screened. CONCLUSION: Overall, the level of CRC screening participation was low and the vast majority of screening tests undertaken were inappropriate in terms of timing, modality, or frequency

Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening

AIM: To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. METHODS: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. RESULTS: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. CONCLUSION: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories

Twin birth changes DNA methylation of subsequent siblings

We asked if twin birth influences the DNA methylation of subsequent siblings. We measured whole blood methylation using the HumanMethylation450 array for siblings from two twin and family studies in Australia and Korea. We compared the means and correlations in methylation between pairs of siblings born before a twin birth (BT siblings), born on either side of a twin birth (B/AT pairs) and born after a twin birth (AT siblings). For the genome-wide average DNA methylation, the correlation for AT pairs (rAT) was larger than the correlation for BT pairs (rBT) in both studies, and from the meta-analysis, rAT = 0.46 (95% CI: 0.26, 0.63) and rBT = -0.003 (95% CI: -0.30, 0.29) (P = 0.02). B/AT pairs were not correlated (from the meta-analysis rBAT = 0.08; 95% CI: -0.31, 0.45). Similar results were found for the average methylation of several genomic regions, e.g., CpG shelf and gene body. BT and AT pairs were differentially correlated in methylation for 15 probes (all P < 10-7), and the top 152 differentially correlated probes (at P < 10-4) were enriched in cell signalling and breast cancer regulation pathways. Our observations are consistent with a twin birth changing the intrauterine environment such that siblings both born after a twin birth are correlated in DNA methylation