BackgroundSocial media is being used by various stakeholders among pharmaceutical companies, government agencies, health care organizations, professionals, and news media as a way of engaging audiences to raise disease awareness and ultimately to improve public health. Nevertheless, it is unclear what effects this health information has on laypeople.ObjectiveThis study aimed to provide a detailed examination of how promotional health information related to Lynch syndrome impacts laypeople’s discussions on a social media platform (Twitter) in terms of topic awareness and attitudes.MethodsWe used topic modeling and sentiment analysis techniques on Lynch syndrome–related tweets to answer the following research questions (RQs): (1) what are the most discussed topics in Lynch syndrome–related tweets?; (2) how promotional Lynch syndrome–related information on Twitter affects laypeople’s discussions?; and (3) what impact do the Lynch syndrome awareness activities in the Colon Cancer Awareness Month and Lynch Syndrome Awareness Day have on laypeople’s discussions and their attitudes? In particular, we used a set of keywords to collect Lynch syndrome–related tweets from October 26, 2016 to August 11, 2017 (289 days) through the Twitter public search application programming interface (API). We experimented with two different classification methods to categorize tweets into the following three classes: (1) irrelevant, (2) promotional health information, and (3) laypeople’s discussions. We applied a topic modeling method to discover the themes in these Lynch syndrome–related tweets and conducted sentiment analysis on each layperson’s tweet to gauge the writer’s attitude (ie, positive, negative, and neutral) toward Lynch syndrome. The topic modeling and sentiment analysis results were elaborated to answer the three RQs.ResultsOf all tweets (N=16,667), 87.38% (14,564/16,667) were related to Lynch syndrome. Of the Lynch syndrome–related tweets, 81.43% (11,860/14,564) were classified as promotional and 18.57% (2704/14,564) were classified as laypeople’s discussions. The most discussed themes were treatment (n=4080) and genetic testing (n=3073). We found that the topic distributions in laypeople’s discussions were similar to the distributions in promotional Lynch syndrome–related information. Furthermore, most people had a positive attitude when discussing Lynch syndrome. The proportion of negative tweets was 3.51%. Within each topic, treatment (16.67%) and genetic testing (5.60%) had more negative tweets compared with other topics. When comparing monthly trends, laypeople’s discussions had a strong correlation with promotional Lynch syndrome–related information on awareness (r=.98, P<.001), while there were moderate correlations on screening (r=.602, P=.05), genetic testing (r=.624, P=.04), treatment (r=.69, P=.02), and risk (r=.66, P=.03). We also discovered that the Colon Cancer Awareness Month (March 2017) and the Lynch Syndrome Awareness Day (March 22, 2017) had significant positive impacts on laypeople’s discussions and the...