paywalled: Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]

Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]:

Purpose
To estimate the likely number and predictive strength of cancer-associated single nucleotide polymorphisms (SNPs) that are yet to be discovered for seven common cancers.

Methods
From the statistical power of published genome-wide association studies, we estimated the number of undetected susceptibility loci and the distribution of effect sizes for all cancers. Assuming a log-normal model for risks and multiplicative relative risks for SNPs, family history (FH), and known risk factors, we estimated the area under the receiver operating characteristic curve (AUC) and the proportion of patients with risks above risk thresholds for screening. From additional prevalence data, we estimated the positive predictive value and the ratio of non–patient cases to patient cases (false-positive ratio) for various risk thresholds.

Results
Age-specific discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of patients in the highest decile of population risk ranged from 16.2% for ovarian cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were 241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast cancer in women age 50 to 54 or 40 to 44 years, respectively.

Conclusion

Foreseeable common SNP discoveries may not permit identification of small subsets of patients that contain most cancers. Usefulness of screening could be diminished by many false positives. Additional strong risk factors are needed to improve risk discrimination.

paywalled: Japanese Journal of Clinical Oncology- LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis

LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis:

Objective
Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is an important novel gene associated with the proliferation and differentiation of cells. Recent studies have shown that it was overexpressed in many cancer tissues. This study investigated the association between different LAPTM4B polymorphisms and the susceptibility and prognosis of ovarian cancer.

Methods
A case–control study was performed in 282 patients with ovarian cancer and 365 control subjects. Genomic DNA was extracted from peripheral blood lymphocytes in all participants. LAPTM4B genotypes were determined using polymerase chain reaction.

Results
There was a significantly higher LAPTM4B*2 allele frequency in ovarian cancer cases than controls (P < 0.05). Using the LAPTM4B*1/1 genotype as the reference, we found that the LAPTM4B*1/2 and LAPTM4B*2/2 genotypes were positively associated with ovarian cancer.

abstract: DNA repair gene polymorphisms and risk of early onset colorectal cancer in Lynch syndrome (eg. BRCA2, MSH3 (polymorphisms)...)

DNA repair gene polymorphisms and risk of early onset colorectal cancer in Lynch syndrome:

Source:Cancer Epidemiology, Volume 36, Issue 2


DNA repair plays a pivotal role in maintaining genomic integrity with over 130 genes involved in various repair pathways that include base excision repair, nucleotide excision repair, double strand break repair and DNA mismatch repair. Polymorphisms within genes that are involved in these processes have been widely reported to be associated with cancer susceptibility in an extensive range of malignancies that include colorectal cancer (CRC).

Lynch syndrome is caused by inherited germline mutations in DNA mismatch repair genes, predominantly in MLH1 and MSH2, that predispose to a variety of epithelial malignancies, most notably CRC. Despite being a relatively well understood hereditary cancer syndrome there remain several questions in relation to genetic influences on disease expression. Since Lynch syndrome is associated with a breakdown in DNA mismatch repair variation in other DNA repair genes may influence disease expression.

In this report we have genotyped 424 Australian and Polish Lynch syndrome participants for eight common DNA repair gene polymorphisms to assess any association with the age of CRC onset.

 The DNA repair gene SNPs included in the study were: BRCA2 (rs11571653), MSH3 (rs26279), Lig4 (rs1805386), OGG1 (rs1052133), XRCC1 (rs25487), XRCC2 (rs3218536 and rs1799793) and XRCC3 (rs861539). Cox multi-variant regression modelling failed to provide any convincing evidence of an effect in any of the polymorphisms analysed. The data suggest that polymorphisms in DNA repair genes do not contribute to cancer risk in a population of CRC patients who are at increased risk of disease as a result in a deficiency of DNA mismatch repair.

Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population ( IVS10+12G>A and IVS12−6T>C )

Polymorphisms inMSH2gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population

Background:
Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA.

Conclusion:
The IVS10+12G>A and IVS12−6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.

Correction: ABCB1 (MDR1) Polymorphisms and Progression-Free Survival among Women with Ovarian Cancer following Paclitaxel/Carboplatin Chemotherapy

link to original article:

The authors of this article (Clin Cancer Res 2008;14:5594-601), which was published in the September 1, 2008, issue of Clinical Cancer Research (1), wish to inform the scientific community that the results of the analysis of the ABCB1 3435C>T and 1236C>T SNPs presented were incorrectly reported due to a corrupted analysis file.

Platinum sensitivity-related germline polymorphism discovered via a cell-based approach and analysis of its association with outcome in ovarian cancer patients (rs1649942)

health media: BRCA1 Breast Cancer Risk Linked To Other Genes

"...People who carry certain mutations of the BRCA1 gene are known to have a higher risk of developing breast cancer.

Couch told the media that their findings should be "useful in helping determine individual risk for breast cancer in BRCA1 carriers".

"It also provides insights into hormone-receptor-negative breast cancer in the general population," he added.

For the study, Couch and colleagues conducted four phases of genome-wide association studies (GWAS) that altogether involved 20 research centers in 10 North American and European countries and Israel.

For the first phase, to identify candidate gene variants, they scanned the genomes of 1,193 carriers of BRCA1 mutations who were under 40 and had invasive breast cancer and compared them to scans of about the same number of controls: BRCA1 carriers of similar age who did not have breast cancer.

In comparing the genomes from the two populations the researchers examined over half a million genetic alterations. They found 96 pieces of DNA called SNPs, or "snips", short for single nucleotide polymorphisms, that they thought would be likely candidates because they differed between the two populations...."cont'd

Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: A study from the NHANES (National Health and Nutrition Examination Surveys)

Abstract

Objectives

Ecological studies have long described a higher incidence of ovarian cancer in more extreme latitudes, where sun exposure, and presumably vitamin D exposure, is lower. Basic science studies have also noted polymorphisms of the vitamin D receptor in ovarian cancers. The aim of this study is to examine the relationship of serum vitamin D to ovarian cancer.

Conclusions

Prevalent ovarian cancer cases have lower serum 25-hydroxyvitamin D (25[OH]D) than the general population. Deficiency in vitamin D may provide an etiologic link between the long-known ecologic findings regarding latitude and the basic science noting polymorphisms in the vitamin D receptor.

Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium — Cancer Epidemiology, Biomarkers & Prevention

Note: abstract onlyOR = overall risk; 1.0+ denotes an increased risk;
in this study, mucinous cell type was the key finding
Methods:Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin.

Results: The five polymorphisms were not associated with ovarian carcinoma overall ; however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P_{heterogeneity} = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).

Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. 

Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.