Well conserved or coding variants in the linkage region on chromosome 4.

1<p>Phastcons and GERP are both regional conservation algorithms ranging from 0 to 1 and −12.3 to 6.17 respectively (1 and 6.17 being most conserved).</p>2<p>Grantham = 45, PolyPhen prediction = Benign.</p

Linkage on chromosome 4 for the families in which multiple tumours showed the “22-gain-like” aCGH profile.

<p>The LOD-score was calculated under the assumption of homogeneity. The dashed lines indicate the maximum LOD-score -1interval. The X-axis shows the position on chromosome 4 in centimorgan and the markers with a LOD score >0 are indicated. The highest LOD score of 2.49 was located at marker D4S405.</p

General characteristics of the mismatch repair gene mutation carriers in the GEOLynch prospective cohort study.

<p>a College or university degree</p><p>b Highest tertile of the physical activity score</p><p>c CRC =  colorectal cancer</p><p>d History of colorectal adenoma and/or carcinoma</p><p>e Use of any dietary supplement during the last month</p><p>f E.g. glucosamine/chondroitin supplements, and garlic pills</p

Pedigrees of the families in which multiple tumours showed the “22-gain-like” aCGH profile.

<p>Individuals affected with breast cancer are represented by a filled square or circle. Individuals affected by another type of cancer are represented by a square or circle with a vertical black stripe. Below the age at diagnosis and type of cancer can be found: B stands for breast cancer, Li or liver cancer, S for stomach cancer, Oes for oesophagus cancer, C for colon cancer, M for melanoma, Cvx for Cervix cancer, K for kidney cancer, P for prostate cancer and U for type of cancer unknown. Arrows point at the individuals at whose DNA was used for exome sequence. Individuals with tumours with and without the “22-gain-like profile” are represented by “22+”and “22−”.</p

Possibly damaging or well conserved variants in genes encoding proteins involved in DNA integrity maintaince.

<p>Variants were selected if either of these criteria was met: Grantham score>100, GERP conservation score>3, PhastCons conservation score>0.7, or a “Probably damaging” Polyphen2 prediction.</p>1<p>Phastcons and GERP are both regional conservation algorithms ranging from 0 to 1 and −12.3 to 6.17 respectively (1 and 6.17 being most conserved).</p

General characteristics of the mismatch repair gene mutation carriers stratified by dietary supplement use in the GEOLynch prospective cohort study.

<p>a Use of any dietary supplement during the last month</p><p>b No use of dietary supplement during the last month</p><p>c College or university degree</p><p>d Highest tertile of the physical activity score <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066819#pone.0066819-Pols1" target="_blank">[31]</a></p><p>e CRC =  colorectal cancer</p><p>f History of colorectal adenoma and/or carcinoma</p><p>g E.g. glucosamine/chondroitin supplements, and garlic pills</p><p>h Calculated using Mann-Whitney U test for continuous variables or the χ2 test for categorical variables</p

Association of any dietary supplement use and colorectal adenoma risk stratified for smoking status and total fruit and vegetables intake in the GEOLynch prospective cohort study of MMR gene mutation carriers.

<p>a No use of dietary supplements during the last month</p><p>b Use of any dietary supplement during the last month</p

Association of dietary supplement use and colorectal adenoma risk in the GEOLynch prospective cohort study of MMR gene mutation carriers.

<p>a No use of dietary supplements during the last month</p><p>b Use of any dietary supplement during the last month</p

SNP Filtering Summary.

<p>Variant filtering representation through the number of SNPs remaining after the various filtering steps.</p><p>The Average and Percentage remaining rows represent the average number of variants and percentage of variants remaining per family.</p>a<p>Intronic, intergenic and synonymous variants were discarded. See methods.</p>b<p>Detailed criteria for these filters is reported on the methods section.</p>c<p>Number of variants shared between the two individuals in the family.</p>d<p>Total number of final variants for all the individuals in this study.</p

Summary of the data analysis pipeline followed in the present study.

<p>Raw sequencing data was screened for common artifacts prior to the alignment step in a first quality control phase (QC1). High quality (QC2) genome matches were analyzed for variants, in the form of departures from a consensus reference genome. Subsequently, variants were filtered by keeping those common to both members in each family and then discarding variants present in HapMap controls and dbSNP130. Further filtering by variant consequence, score and gene function (see material and methods for details) resulted in a list of 67 snps and 14 indel candidate variants.</p