Furthermore, increased risk of breast cancer with PBC was found in only three studies,11, 12, 26 all of which were conducted before 1990. These results further quantitatively confirmed the conclusion by Piscaglia and Sagrini,8 who suggested that the incidence of breast cancer was not increased in PBC patients and a higher reported incidence may be attributed to immunosuppressive agents, which were used

commonly before 1990. Moreover, the present meta-analysis also did not show any significant association between PBC and several other site-specific malignancies including colon cancer, rectum cancer, colorectal cancer, lung Akt inhibitor cancer, kidney cancer, esophagus cancer, uterus cancer, cervical cancer, prostate cancer, bladder cancer, thyroid cancer, skin melanoma, skin nonmelanoma

malignancy, Hodgkin disease, and non-Hodgkin lymphoma. However, the conclusion should be addressed with caution, since subgroup meta-analysis could not be performed for these malignancies due to too small number of available studies. The present study has some limitations that should be addressed. First, the study included a wide variety of articles that looked at risks of Crenolanib molecular weight malignancy in PBC. Therefore, we had to acknowledge that the specific differences between those articles which could account for different results might be a potential source of bias. Second, we could not include some studies that failed to report data with which relative risk of some cancers could be calculated. These unidentified studies may reduce the power of our analysis, but were unlikely to bias its results. Third, the impact of confounding inherent in the included studies can not be completely 上海皓元 excluded, which might bias the results either toward overestimation or underestimation of risk estimates. Although subgroup analyses

with some known confounders such as age, sex, region, case ascertainment, and type of effect size were performed for overall cancer, HCC and breast cancer risks, other confounders cannot be excluded as a potential explanation for the observed findings. Furthermore, for other cancer risks, subgroup analyses could not be performed due to the small number of studies. Fourth, as described in the previous study, it is impossible to completely exclude potential publication bias because small studies with null results tend not to be published,36 even though no significant publication bias was found by funnel plot analysis and formal statistical tests. Finally, data regarding PBC and risks of the majority of malignancies were extremely sparse, limiting our ability to draw firm conclusions. In conclusion, the present systematic review and meta-analysis demonstrated that PBC is significantly associated with increased risk of overall malignancy, especially with HCC.