1523P - The 8.1 ancestral haplotype is strongly associated with the risk of small cell lung cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Small-Cell Lung Cancer
Presenter Judit Kocsis
Authors J. Kocsis1, L. Graf1, A. Szilagyi2, B. Dome3, L. Tamasi4, G. Galffy4, Z. Orosz5, Z. Prohaszka2, G. Fust2, Z. Bartfai6
  • 13rd Dept Of Internal Medicine, Oncology, Semmelweis University, 1125 - Budapest/HU
  • 23rd Dept Of Internal Medicine, Semmelweis University, 1125 - Budapest/HU
  • 3Tumor Biology, National Koranyi Institute of Pulmonology, 1121 - Budapest/HU
  • 4Pulmonology, Semmelweis University, 1125 - Budapest/HU
  • 5Radiology And Oncotherapy, Semmelweis University, 1089 - Budapest/HU
  • 6Pulmonology, Erzsebet Hospital, 9400 - Sopron/HU

Abstract

Background

It is well established that the risk of lung cancer is related to the individual genetic background as it is reflected in the increased incidences among first degree relatives. The discovery of these genetic variations can lead to the identification of those individuals who are at high risk of developing lung cancer. AH8.1 is a haplotype which extends through the whole MHC region in the short arm of chromosome 6. It is the most frequent and a very conservative haplotype in the Caucasian population. Previously we have reported a strong association between AH8.1 and colorectal cancer with an odds ratio higher than any risks reported for SNPs in genome-wide association studies or candidate gene studies. Published data indicate that AH8.1 is a strong risk factor for ovarian cancer and for non-Hodgkin lymphoma as well.

Aim/methods

Here we have determined the carrier state of AH8.1 in 102 patients with small cell lung cancer (SCLC) (62 + 7.8 years), 94 patients with non- SCLC (NSCLC) (59+ 8.6 years) and in 248 age-matched control subjects (66.7 + 6.5 years). Subjects carrying all the four marker alleles of AH8.1 (C allele of AGER 429T > C, G allele of HSP70-2 1267A > G, A allele of TNFalpha -308G > A, as well as G allele of LTA 252A > G polymorphisms) were considered as AH8.1 carriers.

Results

23% (23/102) of SCLC patients, 13.8% (13/94) of NSCLC patients, and 13% (32/248) of healthy controls carried the AH8.1 haplotype. We have found a significant increased risk for SCLC in those people carrying AH8.1 with an odds ratio of 1.94 (1.01-3.73; p = 0.046) (for men: 3.09, 1.07-8.82; p = 0.031). However, there was no significant increase in the risk for NSCLC.

Summary

These findings indicate that carriers of the AH8.1 haplotype are at increased risk for SCLC and it can be due to the altered immune response that is characteristic for 8.1 AH.

Disclosure

All authors have declared no conflicts of interest.