Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

<p>Abstract</p> <p>Background</p> <p>The ATM protein is activated as a result of ionizing radiation, and genetic variants of the <it>ATM </it>gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for <it>ATM </it>mutations have been reported to have an increased risk of malignancy, especially breast cancer.</p> <p>Materials and methods</p> <p>Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the <it>ATM </it>gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant.</p> <p>Results and Conclusion</p> <p>A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the <it>ATM </it>gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient material.</p

Differences in serum levels of CB-153 and p,p '-DDE, and reproductive parameters between men living south and north in Norway

Arctic is contaminated with persistent organochlorine pollutants (POPs), and exposure to these compounds may differ between south and north in Norway. POPs may have negative impact on male reproductive characteristics. We compared serum levels of the CB-153 and p,p'-DDE in men who were born and had lived most of their lifetime south and north (close to or above the Arctic Circle) in Norway. We found no geographical differences in levels of CB-153 (south: 50 ng/g lipid (mean), north: 59 ng/g lipid; p = 0.27) or sperm parameters. However, the levels of AV-ODE were higher in south than in north (81 ng/g lipid (mean) vs. 66 ng/g lipid; p = 0.02), as were the levels of total and free testosterone. The FSH levels were lowest in south. A strong relationship between the CB-153 and the SHBG levels was observed. The regional differences observed for p,p'-DDE, testosterone and FSH were not reflected in the semen quality. (C) 2011 Elsevier Inc. All rights reserved