BMC Cancer 2002, 2 http://www.biomedcentral.com/1471-2407/2/26 Table 5: SIR values(95%CI) in relation to overall cancer incidence and some selected tumour types and laterality and bilaterality at di- agnosis of gynecomastia. Included are only prospective cases. Tumour type all sites testicle esophagus skin cancer (melanoma excl.) number personyears Unilateral right 1.22(0.89–1.71) 4.03(0.10–22.97) 6.11(0.74–22.08) 2.44(0.67–6.29) 196 3588 may have substantially reduced the risk for carcinoma as prophylactic operations or reduction mammoplastic sur- gery previously has been shown to reduce the risk of breast cancer in women [17,18]. Liver injury may be asso- ciated with gynecomastia [2] and in our series chronic al- coholism was present in 7 cases of which two had known cirrhosis. The increased risk of esophagus cancer may be another indicator of alcoholism and secondary liver inju- ry in a subset of the patients [19]. All cases of esophageal cancer occurred in individuals with a gynecomastia diag- nosis after the age of 50 years. We have no explaination for the higher risk of squamous cell carcinoma of the skin. No study has previously associated development of squa- mous cell carcinoma with gynecomastia and the finding needs to be confirmed in future studies, although the risk relationship in our study was strong. The reason for the re- lationship is unclear as the development of skin tumours in general has not been associated with hormonal risk fac- tors. That some skin tumours are due to papilloma virus infections could lend support to a theory of increased vi- rus activity/effects in individuals exposed to estrogens as is the case in cervical carcinoma and its virus related carcino- genesis due to papilloma virus [20]. Also synergistic ac- tion between chronic estrogen exposure and the oncogenes of HPV16 that coordinates squamous carcino- genesis in the female reproductive tract of K14-HPV16 transgenic mice has been found [21]. HPV16 is however confined to mucous membranes and it is not known if other HPV types in a similar matter would interact in the skin with estrogen. A decreased risk of rectal carcinoma was noted, and we have no biological explaination for this finding although it has long been known that females have a lower death rate and risk of the tumour [22]. It is notable that among the 13 skin tumours 5 occurred in individuals with multiple squamous cell carcinomas of the skin. Including tumours occurring prior to gyneco- Gynecomastia left 0.90(0.60–1.31) 9.26(1.12–33.47) 0.00(0.00–10.22) 4.18(1.80–8.24) 194 3910 Bilateral 0.87(0.35–1.79) 0.00(0.00–71.05) 10.33(0.26–57.55) 1.99(0.05–11.06) 55 878 mastia 8 individuals of 9 had multiple tumours of the skin. The age at diagnosis of skin cancer was above 50 years of age in all cases, and the risk increased with longer follow up and was evident both for cases with a gyneco- mastia diagnosis before as well as after 50 years of age. From a clinical point of view it is questionable whether screening of tumours woul dbe worth while in patients with gynecomastia. On the other hand, the two tumours most clearly displaying an increased risk, ie.testicular car- cinoma and squamous skin cancer rather easily can be screened by general examination. If also male breast can- cer is included as a risk a possible clinical work up in a man presenting with gynecomastia should evaluate the following points; is there a endogenous or exogenous hor- monal cause?; has the patient been taking drugs that may cause gynecomastia?; is there a known accompanying dis- ease causing a liver or gonadal injury?; can tumour disease in testis, skin and breast be excluded on clinical grounds?. For men with a gynecomastia diagnosis a after 50 years of age the risk of testicular cancer is negligible whilst a gyne- comastia diagnosis before and after 50 years of age may both indicate an increased the risk for skin cancer. Conclusions In conclusion the prospective investigation confirms an increased risk for testicular cancerin men with a prior his- tory of gynecomastia. Also skin cancer and esophageal cancer were morecommon among men with gynecomas- tia. No prospective case of male breast carcinoma was seen, although two male breast cancer cases occurred prior to gynecomastia diagnosis. Competing interests None declared. Page 5 of 6 (page number not for citation purposes)