INTRODUCTION: In the Philippines, lung, breast, colon-rectum, and oral cavity cancers are among the top 10 most common cancers. This study evaluates the risk factors for these cancers among Filipinos.

METHODS: This age-matched case-control study included incident primary cancers (histologically-diagnosed) of the lung, breast (also matched for sex), colon-rectum and oral cavity. Controls (clinically free and no history of cancer) were obtained from the same tertiary hospitals as the cases. Target sample size was 283 cases and 283 controls per cancer type. Conditional logistic regression was done.

RESULTS: Exposure to cigarette/tobacco was a significant risk factor for lung (OR of current smoker compared to non-smoker [95% Confidence Interval]: 3.6 [1.6-7.9]) and oral cavity cancers (2.0 [1.2-3.3]); family history (1st degree) for lung (4.3 [1.314.2]) and breast cancers (3.0 [1.2-7.5]); every year increase in age at first pregnancy for breast cancer (1.06 [1.02-1.11]). Other risk factors for oral cavity were passive smoking (2.8 [1.6-5.1]), chewing tobacco (5.2[1.4-19.5]) and inverted cigarette smoking (3.2[1.3-8.1]). Fish sauce (patis) was found to be a protective factor for breast cancer (0.34 [0.22-0.51]) and oral cavity (0.44 [0.25-0.78]) and use of shrimp paste (bagoong) (0.48 [0.27-0.84]) for oral cavity.

CONCLUSION AND RECOMMENDATIONS: Except for family history of cancer, the identified risk factors for lung, colon-rectum, and oral cavity cancers are preventable. Proper diet and lifestyle, avoidance of cigarettes and tobacco, and environmental safety in the workplace are key cancer prevention measures. Public awareness campaign and continuing healthcare provider education must always be part of a cancer prevention program.

Pregnancy ; Tobacco ; Tobacco, Smokeless ; Tobacco Smoke Pollution ; Cigarette Smoking ; Rectum ; Smokers ; Smoking ; Breast Cancer 3 ; Breast Neoplasms ; Mouth Neoplasms ; Health Personnel ; Colon

The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. Consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3CA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3CA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors. This effort will be important to prevent or explain therapeutic failures and select patients who are most likely to respond to new therapies that inhibit the PI3K pathway.
Antineoplastic Agents, Hormonal ; therapeutic use ; Apoptosis ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Cellular Senescence ; Class I Phosphatidylinositol 3-Kinases ; Disease-Free Survival ; Early Detection of Cancer ; Female ; Humans ; Mutation ; Neoplasm Metastasis ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; genetics ; metabolism ; Survival Rate