The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study

被引：25

作者：

Carreras-Torres, Robert ^{[1
]}

Haycock, Philip C. ^{[2
]}

Relton, Caroline L. ^{[2
]}

Martin, Richard M. ^{[2
,3
,4
]}

Smith, George Davey ^{[2
]}

Kraft, Peter ^{[5
]}

Gao, Chi ^{[5
]}

Tworoger, Shelley ^{[5
,6
,7
]}

Le Marchand, Loic ^{[8
]}

Wilkens, Lynne R. ^{[8
]}

Park, Sungshim L. ^{[9
]}

Haiman, Christopher ^{[9
]}

Field, John K. ^{[10
]}

Davies, Michael ^{[10
]}

Marcus, Michael ^{[10
]}

Liu, Geoffrey ^{[11
]}

Caporaso, Neil E. ^{[12
]}

Christiani, David C. ^{[5
,13
,14
]}

Wei, Yongyue ^{[5
,13
,14
]}

Chen, Chu ^{[15
]}

Doherty, Jennifer A. ^{[16
]}

Severi, Gianluca ^{[17
]}

Goodman, Gary E. ^{[18
]}

Hung, Rayjean J. ^{[19
]}

Amos, Christopher I. ^{[20
]}

McKay, James ^{[1
]}

Johansson, Mattias ^{[1
]}

Brennan, Paul ^{[1
]}

机构：

[1] IARC, Genet Sect, Lyon, France

[2] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[3] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Unit Nutr Diet & Lifestyle, Bristol BS2 8AE, Avon, England

[4] Univ Bristol, Bristol BS2 8AE, Avon, England

[5] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[6] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[7] Harvard Med Sch, Boston, MA USA

[8] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA

[9] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[10] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Canc Med, Roy Castle Lung Canc Res Programme,Canc Res Ctr, Liverpool, Merseyside, England

[11] Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON, Canada

[12] NCI, Genet Epidemiol Branch, DCEG, NIH, Rockville, MD USA

[13] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA

[14] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA

[15] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA

[16] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA

[17] Human Genet Fdn HuGeF, Turin, Italy

[18] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[19] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[20] Dartmouth Coll, Geisel Sch Med, Dept Biomed Data Sci, 1 Med Ctr Dr, Lebanon, NH 03756 USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

RISK; ASSOCIATION; VARIANTS; INSIGHTS; OBESITY;

D O I：

10.1038/srep31121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 x 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.

引用

页数：6

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