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Lophatananon, A.

Publications and source records attributed to Lophatananon, A..

2 recordsLinked to original sources
bioRxiv2018

Evaluating causal associations between previously reported risk factors and epithelial ovarian cancer: a Mendelian randomization analysis

BackgroundPreviously reported observational associations between risk factors and epithelial ovarian cancer (EOC) could reflect residual confounding, reverse causation, or measurement error. Mendelian randomization (MR) uses genetic variants as proxies for modifiable risk factors to strengthen causal inference in observational studies.\n\nMethodsWe used MR to evaluate the causal role of 13 previously reported risk factors in overall and histotype-specific EOC in up to 25,509 case subjects and 40,941 controls in the Ovarian Cancer Association Consortium. Inverse-variance weighted models were employed to generate effect estimates and MR-Egger, weighted median, and weighted mode were performed to examine evidence of horizontal pleiotropy. A Bonferroni-corrected P-value threshold was used to establish \"strong evidence\" (P<0.0038) and \"suggestive evidence\" (0.0038<P<0.05) for associations.\n\nResultsThere was strong or suggestive evidence that 9 of 13 risk factors were causally associated with overall or histotype-specific EOC. Genetic liability to endometriosis was strongly associated with EOC (OR per log odds higher liability: 1.27,95%CI:1.16-1.40;P=6.94x10-7) and lifetime smoking exposure was suggestively associated with EOC (OR per unit increase in smoking score:1.36,95%CI:1.04-1.78;P=0.02). In histotype-stratified analyses, the strongest associations found were between: height and clear cell carcinoma (OR per SD increase:1.36,95%CI:1.15-1.61;P=0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset:1.09,95% CI:1.02-1.16;P=0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per log odds higher liability:0.74,95% CI:0.62-0.90;P=0.002). There was little evidence that genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone-binding globulin were associated with ovarian cancer or its subtypes.\n\nConclusionsOur comprehensive examination of possible etiological drivers of ovarian carcinogenesis supports a causal role for few of these factors in epithelial ovarian cancer and suggests distinct etiologies across histotypes.

epidemiology↗
bioRxiv2018

The association between weight at birth and breast cancer risk revisited using Mendelian randomisation

Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 x 10-8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW; 95% confidence interval: 0.73--1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer. Thus, there is little evidence from MR to suggest that the previously observed association between higher BW and increased risk of breast cancer in adult life is causal.

epidemiology↗