砷為人類皮膚致癌物。臺灣流行病學研究顯示砷暴露量會與皮膚癌發生機會呈現劑量效應關係，然而砷致癌機轉仍不明確；先前研究認為砷暴露會提高染色體不穩定性，進而提高罹癌風險。p21 Ser31Arg與p53 Arg72Pro調節細胞週期之基因，會製造參與細胞週期之特定蛋白質來參與細胞週期、輔助細胞分裂，並會於基因損傷時做出反應，進而中斷細胞週期、可能會誘導走向細胞凋亡。有研究顯示此兩種基因多型性與染色體不穩定性有關，並會增加癌症易感性。由於每個人遺傳變異性不同可能導致罹病風險不同，因此，本研究目的在於探討砷攝取、調節細胞週期之基因多型性與皮膚癌之相關性。本研究為病例對照研究，將經醫師診斷為皮膚癌的患者列為病例組，以無任何癌症且年齡大於50歲者為對照組，全部研究對象皆接受問卷調查，了解基本人口學變項，並收集飲水史與居住史以利評估砷暴露情況，同時採集血液樣本作基因型分析。使用t-test與χ2 test 比較兩組間差異後發現罹患皮膚癌者其平均年齡較大(p<0.01)、教育程度較低(p<0.01)，飲用井水超過(含)15年且飲用當地井水砷含量大於0.35 ppm者比例偏高(p<0.01)。且使用邏輯式廻歸(logistic regression)探討發現p21 Ser31Arg與p53 Arg72Pro基因多型性與罹患皮膚癌較無相關，但飲用井水超過(含)15年且飲用當地井水砷含量大於0.35 ppm者其罹患皮膚癌風險高達133倍(95 % 信賴區間：32.7-541.1)。因此，本研究發現調節細胞週期基因p21 Ser32Arg與p53 Arg72Pro之多型性與皮膚癌罹癌風險無關。然而砷暴露與罹患皮膚癌有顯著相關。

Arsenic is a well-documented human carcinogen. The cutaneous effects, including skin cancer, of chronic exposure to high levels of arsenic in drinking water have been demonstrated by epidemiological studies in Taiwan. Cell cycle progression regulated by p21 Ser31Arg and p53 Arg72Pro polymorphism in response to DNA damage may lead to cell cycle arrest at the G1/S checkpoint. Recent studies suggested that p21 Ser31Arg and p53 Arg72Pro are associated with chromosome instability, which increases the risk of developing cancer. To evaluate the relations of arsenic ingestion and genetic polymorphism of regulators of cell cycle progression to skin cancer, we recruited skin cancer patients and cancer-free controls at a teaching hospital in Tainan, Taiwan. Each participant completed a questionnaire, which included questions on gender, age, education, family history, smoking habit, and provided a blood sample for genotyping analysis. We evaluated the differences in characteristics between the cases and controls by using the t-test for continuous data and the chi-square test for categorical data. We found that cases were older (p<0.01), less educated (p<0.01), more likely to live in high-arsenic-level area and drink groundwater for more than 15 years (p<0.01). While high-arsenic-level area and having drunk groundwater for more than 15 years was associated with an increased risk of skin cancer (OR=133, 95 % CI=32.7-541.1), we found no associations between genetic polymorphism of regulators of cell cycle progression and skin cancer.

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