Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Khankari, Nikhil K.; Shu, Xiao‐Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Buracco, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas F.; Eeles, Rosalind; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Wang, Zheng; Study, Colorectal Transdisciplinary; Discovery, Biology

doi:10.1371/journal.pmed.1002118

Cited by 75 publications

(62 citation statements)

References 74 publications

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“…Additionally, there was suggestive evidence of positive associations between height and liver, biliary tract and thyroid cancers. Our findings are consistent with previous MR studies showing a positive association of height with colorectal [50,51], lung [50,52] and breast [53,54] cancer. Increased height is associated with elevated insulin-like growth factor 1 (IGF1), [55] which is a growth factor that drives cellular proliferation and survival and has thus been implicated in carcinogenesis of IGF responsive tissues.…”

Section: Discussionsupporting

confidence: 93%

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

Vithayathil

Carter

Kar

et al. 2020

Preprint

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word count: 299 Main text word count: 2,320 Number of Tables: 5 (supplementary) Number of Figures: 4 ABSTRACT Objectives To investigate the casual role of body mass index, body fat composition and height in cancer. DesignTwo stage mendelian randomisation study SettingPrevious genome wide association studies and the UK Biobank ParticipantsGenetic instrumental variables for body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI) and height from previous genome wide association studies and UK Biobank .Cancer outcomes from 367 586 participants of European descent from the UK Biobank. Main outcome measuresOverall cancer risk and 22 site-specific cancers risk for genetic instrumental variables for BMI, FMI, FFMI and height. ResultsGenetically predicted BMI (per 1 kg/m 2 ) was not associated with overall cancer risk (OR 0.99; 95% confidence interval (CI) 0-98-1.00, p=0.105). Elevated BMI was associated with increased risk of stomach cancer (OR 1.15, 95% (CI) 1.05-1.26; p=0.003) and melanoma (OR 0.96, 95% CI 0.92-1.00; p=0.044). For sex-specific cancers, BMI was positively associated with uterine cancer (OR 1.08, 95% CI 1.01-1.14; p=0.015) but inversely associated with breast (OR 0.95, 95% CI 0.92-0.98; p=0.001), prostate (OR 0.95, 95% CI 0.92-0.99; p=0.007) and testicular cancer (OR 0.89, 95% CI 0.81-0.98; p=0.017). Elevated FMI (per 1 kg/m 2 ) was associated with gastrointestinal cancer (stomach cancer OR 4.23, 95% CI 1.18-15.13, p=0.027; colorectal cancer OR 1.94, 95% CI 1.23-3.07; p=0.004). Increased height (per 1 standard deviation, approximately 6.5cm) was associated with increased risk of overall cancer (OR 1.06; 95% 1.04-1.09; p = 2.9710 -8 ) and most site-specific cancers with the strongest estimates for kidney, non-Hodgkin lymphoma, colorectal, lung, melanoma and breast cancer. ConclusionsThere is little evidence for BMI as a casual risk factor for cancer. BMI may have a causal role for sexspecific cancers, although with inconsistent directions of effect, and FMI for gastrointestinal malignancies. Elevated height is a risk factor for overall cancer and multiple site cancers.

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Section: Discussionsupporting

confidence: 93%

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

Vithayathil

Carter

Kar

et al. 2020

Preprint

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“…A Korea cohort study reported each 5-cm increment in height was associated with increased risk of lung cancer. 13 Similar associations were also recorded in two recent meta-analyses 14,15 ; however, the results from Million Women Study in UK did not find significant associations between height and risk of lung cancer. 16 It remains unclear whether the observed association reflects a causal effect of adult height on lung cancer, or is due to confounding or biases inherent in conventional epidemiological studies.…”

supporting

confidence: 73%

“…Modest association between genetically determined height and risk of lung cancer, based on European population, was reported using MR analysis. Moreover, the increased risk for lung adenocarcinoma appears to be stronger than lung squamous cell carcinoma . Our results are in line with previous observational study in Korean population and the height MR study.…”

Section: Discussionmentioning

confidence: 99%

Genetically determined height was associated with lung cancer risk in East Asian population

et al. 2018

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The association between adult height and risk of lung cancer has been investigated by epidemiology studies, but the results are inconsistent. Mendelian randomization (MR) analyses with individual‐level data from two genome‐wide association studies, including a total of 7127 lung cancer cases and 6818 controls, were carried out to explore whether adult height is causally associated with risk of lung cancer. A weighted genetic risk score (wGRS) was created based on genotypes of 101 known height‐associated genetic variants. Association between the wGRS and risk of lung cancer was analyzed by logistic regression for each study separately. The combined effect was calculated using fixed effect meta‐analysis. MR analyses showed that increased risk of lung cancer (OR = 1.19, 95%CI: 1.05‐1.35, P = 0.006) associated with taller genetically determined height. Compared with individuals in the lowest tertile of the height‐associated wGRS, those in the highest tertile had 1.10‐fold (95% CI: 1.01‐1.20) increased risk of developing lung cancer. Sensitivity analyses excluding BMI‐associated genetic variants demonstrated consistent association. Our study suggested that genetically taller height was associated with increased risk of lung cancer in East Asian population, indicating that increasing height may have a causal role in lung cancer carcinogenesis.

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“…Our data suggest a 1.10-fold increase in osteosarcoma risk per standard deviation in polygenic height score, which corresponds to an approximately 1.7-cm increase in stature. This can be re-scaled to make direct comparisons with a previous Mendelian randomization study that reported effects sizes per 10-cm increase in genetically-predicted height 45 . While they observed an approximately 10% increased risk of lung cancer, 20% increased risk of breast cancer, and 60% increased risk of colorectal cancer associated with each 10-cm increase in genetically-predicted adult height, our re-scaled estimate is equivalent to a 75% increase in osteosarcoma risk per 10-cm increase in adult height.…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of childhood and adult height associated with osteosarcoma risk

Zhang

Morimoto

Smith

et al. 2018

Cancer

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Background: Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, the relative contribution of stature during different developmental time-points remains unclear. Furthermore, how genetic determinants of height impact osteosarcoma etiology remains unexplored. Genetic variants associated with stature in previous genome-wide association studies may be biomarkers of osteosarcoma risk. Methods: We tested the associations between osteosarcoma risk and polygenic scores for adult height (416 variants), childhood height, (six variants), and birth length (five variants) in 864 osteosarcoma patients and 1879 controls of European ancestry. Results: Each standard deviation increase in the polygenic score for adult height, corresponding to a 1.7-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.19, P= 0.027). Each standard deviation increase in the polygenic score for childhood height, corresponding to a 0.5-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.20, P= 0.023). The polygenic score for birth length was not associated with osteosarcoma risk (P=0.11). When adult and childhood height scores were modeled together, they were independently associated with osteosarcoma risk (P=0.037 and 0.043, respectively). An eQTL for CILP2 (cartilage intermediate layer protein 2), rs8103992, was significantly associated with osteosarcoma risk after adjustment for multiple comparisons (OR=1.35, 95% CI: 1.16–1.56, P=7.93×10−5, Padjusted=0.034). Conclusions: Genetic propensity to taller adult and childhood height attainments contributed independently to osteosarcoma risk in our data. These results suggest that the biological pathways affecting normal bone growth may be involved in osteosarcoma etiology.

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Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Cited by 75 publications

References 74 publications

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

Genetically determined height was associated with lung cancer risk in East Asian population

Genetic determinants of childhood and adult height associated with osteosarcoma risk

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