Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution

Sari Tuupanen, Iina Niittymäki, Kari Juhani Nousiainen, Sakari Vanharanta, Jukka-Pekka Mecklin, Kyösti Nuorva, Heikki Järvinen, Sampsa Hautaniemi, Auli Karhu, Lauri A Aaltonen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

"A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95% confidence interval (CI), 1.08-1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95% CI, 1.02-1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95% CI, 1-1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22%). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC."
Original languageEnglish
JournalCancer Research
Volume68
Issue number1
Pages (from-to)14-17
Number of pages4
ISSN0008-5472
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 311 Basic medicine

Cite this

Tuupanen, Sari ; Niittymäki, Iina ; Nousiainen, Kari Juhani ; Vanharanta, Sakari ; Mecklin, Jukka-Pekka ; Nuorva, Kyösti ; Järvinen, Heikki ; Hautaniemi, Sampsa ; Karhu, Auli ; Aaltonen, Lauri A. / Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution. In: Cancer Research. 2008 ; Vol. 68, No. 1. pp. 14-17.
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title = "Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution",
abstract = "{"}A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95{\%} confidence interval (CI), 1.08-1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95{\%} CI, 1.02-1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95{\%} CI, 1-1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22{\%}). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC.{"}",
keywords = "311 Basic medicine",
author = "Sari Tuupanen and Iina Niittym{\"a}ki and Nousiainen, {Kari Juhani} and Sakari Vanharanta and Jukka-Pekka Mecklin and Ky{\"o}sti Nuorva and Heikki J{\"a}rvinen and Sampsa Hautaniemi and Auli Karhu and Aaltonen, {Lauri A}",
year = "2008",
doi = "10.1158/0008-5472.CAN-07-5766",
language = "English",
volume = "68",
pages = "14--17",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "1",

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Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution. / Tuupanen, Sari; Niittymäki, Iina; Nousiainen, Kari Juhani; Vanharanta, Sakari; Mecklin, Jukka-Pekka; Nuorva, Kyösti; Järvinen, Heikki; Hautaniemi, Sampsa; Karhu, Auli; Aaltonen, Lauri A.

In: Cancer Research, Vol. 68, No. 1, 2008, p. 14-17.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution

AU - Tuupanen, Sari

AU - Niittymäki, Iina

AU - Nousiainen, Kari Juhani

AU - Vanharanta, Sakari

AU - Mecklin, Jukka-Pekka

AU - Nuorva, Kyösti

AU - Järvinen, Heikki

AU - Hautaniemi, Sampsa

AU - Karhu, Auli

AU - Aaltonen, Lauri A

PY - 2008

Y1 - 2008

N2 - "A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95% confidence interval (CI), 1.08-1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95% CI, 1.02-1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95% CI, 1-1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22%). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC."

AB - "A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95% confidence interval (CI), 1.08-1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95% CI, 1.02-1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95% CI, 1-1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22%). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC."

KW - 311 Basic medicine

U2 - 10.1158/0008-5472.CAN-07-5766

DO - 10.1158/0008-5472.CAN-07-5766

M3 - Article

VL - 68

SP - 14

EP - 17

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 1

ER -