Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer

Pengyuan Liu, Haris G. Vikis, Yan Lu, Yian Wang, Ann G. Schwartz, Susan M. Pinney, Ping Yang, Mariza De Andrade, Adi Gazdar, Colette Gaba, Diptasri Mandal, Juwon Lee, Elena Kupert, Daniela Seminara, John Minna, Joan E. Bailey-Wilson, Christopher I. Amos, Marshall W. Anderson, Ming You

Research output: Contribution to journalArticle

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Abstract

Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for. Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio. Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 ×10-4; odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 × 10-6) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers. Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.

Original languageEnglish (US)
Pages (from-to)517-524
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number2
DOIs
StatePublished - Feb 2010

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Genetic Predisposition to Disease
Lung Neoplasms
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Molecular Epidemiology
Population Genetics
Population
Linear Models
Logistic Models
Alleles

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer. / Liu, Pengyuan; Vikis, Haris G.; Lu, Yan; Wang, Yian; Schwartz, Ann G.; Pinney, Susan M.; Yang, Ping; De Andrade, Mariza; Gazdar, Adi; Gaba, Colette; Mandal, Diptasri; Lee, Juwon; Kupert, Elena; Seminara, Daniela; Minna, John; Bailey-Wilson, Joan E.; Amos, Christopher I.; Anderson, Marshall W.; You, Ming.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 2, 02.2010, p. 517-524.

Research output: Contribution to journalArticle

Liu, P, Vikis, HG, Lu, Y, Wang, Y, Schwartz, AG, Pinney, SM, Yang, P, De Andrade, M, Gazdar, A, Gaba, C, Mandal, D, Lee, J, Kupert, E, Seminara, D, Minna, J, Bailey-Wilson, JE, Amos, CI, Anderson, MW & You, M 2010, 'Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 2, pp. 517-524. https://doi.org/10.1158/1055-9965.EPI-09-0791
Liu, Pengyuan ; Vikis, Haris G. ; Lu, Yan ; Wang, Yian ; Schwartz, Ann G. ; Pinney, Susan M. ; Yang, Ping ; De Andrade, Mariza ; Gazdar, Adi ; Gaba, Colette ; Mandal, Diptasri ; Lee, Juwon ; Kupert, Elena ; Seminara, Daniela ; Minna, John ; Bailey-Wilson, Joan E. ; Amos, Christopher I. ; Anderson, Marshall W. ; You, Ming. / Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 2. pp. 517-524.
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title = "Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer",
abstract = "Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for. Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio. Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 ×10-4; odds ratio, 0.57; 95{\%} confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95{\%} confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 × 10-6) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6{\%} of familial lung cancer in smokers. Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.",
author = "Pengyuan Liu and Vikis, {Haris G.} and Yan Lu and Yian Wang and Schwartz, {Ann G.} and Pinney, {Susan M.} and Ping Yang and {De Andrade}, Mariza and Adi Gazdar and Colette Gaba and Diptasri Mandal and Juwon Lee and Elena Kupert and Daniela Seminara and John Minna and Bailey-Wilson, {Joan E.} and Amos, {Christopher I.} and Anderson, {Marshall W.} and Ming You",
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T1 - Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer

AU - Liu, Pengyuan

AU - Vikis, Haris G.

AU - Lu, Yan

AU - Wang, Yian

AU - Schwartz, Ann G.

AU - Pinney, Susan M.

AU - Yang, Ping

AU - De Andrade, Mariza

AU - Gazdar, Adi

AU - Gaba, Colette

AU - Mandal, Diptasri

AU - Lee, Juwon

AU - Kupert, Elena

AU - Seminara, Daniela

AU - Minna, John

AU - Bailey-Wilson, Joan E.

AU - Amos, Christopher I.

AU - Anderson, Marshall W.

AU - You, Ming

PY - 2010/2

Y1 - 2010/2

N2 - Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for. Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio. Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 ×10-4; odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 × 10-6) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers. Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.

AB - Background: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for. Methods: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio. Results: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 ×10-4; odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 × 10-6) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers. Conclusions: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.

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