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Genetic Alterations Can Effect Breast Cancer Risk from Low-Dose Radiation

By MedImaging International staff writers
Posted on 31 Oct 2012
Scientists have identified tissue processes that may influence a woman’s resistance or vulnerability to breast cancer after exposure to low-dose ionizing radiation, such as the levels used in full-body computed tomography (CT) scans and radiotherapy.

The study, conducted by scientist from the US Department of Energy Lawrence Berkeley National Laboratory (Berkeley, CA, USA), could lead to new tools to identify women who have higher or lower risks of breast cancer from low-dose radiation. Such a predictive approach could help guide the treatment of cancer patients who may be better helped by nonradiation techniques.

The findings also back up the hypothesis that an individual’s genes play a big role in understanding her breast cancer risk from low-dose radiation. The current model for predicting cancer risk from ionizing radiation is directly proportionate to dose. But there is mounting appreciation that this linear correlation does not apply at lower doses. Instead, the health effects of low-dose radiation may considerably differ between individuals depending on their genetic makeup.

The scientists, led by Dr. Andy Wyrobek of Berkeley Lab’s life sciences division, reported their research October 19, 2012, in the journal PLOS ONE. They examined mammary tissue from two strains of mice--one that is vulnerable to radiation-induced mammary gland cancer and one that is resistant--before and after the mice were exposed to low-dose radiation.

The investigators then searched for variations between the two strains in how their genes to switch on and off. They employed a technique that scans thousands of genes simultaneously. They found differences in genes that regulate tissue stress response, DNA repair, cellular proliferation, immune response, and other cellular and tissue processes. They also discovered that these disparities carried over to surviving breast cancer in women. Breast cancer patients with gene expression profiles similar to the cancer-resistant mice (before radiation exposure) were more apt to survive eight years after diagnosis. Women with gene expression profiles similar to the cancer-sensitive mice were less likely to survive after eight years.

Based on this, the scientists believe the cellular and tissue processes that regulate the mice’s risk of mammary gland cancer from low-dose radiation are similar to the processes that affect a woman’s chance of surviving breast cancer. “Our studies of genetic differences in radiation sensitivity in mice, and individual variation in breast cancer survival in women, suggest that there are women who, because of their genes, have a higher risk of breast cancer when they’re exposed to low-dose radiation,” said Andy Wyrobek, who conducted the research with Dr. Antoine Snijders, Joe Gray, and several other Berkeley Lab scientists.

“This raises the possibility that we can use gene expression profiles to develop simple tests that screen for women who may be sensitive to low-dose radiation versus women who are resistant,” Dr. Snijders stated.

The scientists first examined the lab mice before exposing them to radiation. They identified more than 130 genes that express differently in blood and mammary tissue samples of cancer-resistant mice compared to cancer-sensitive mice. To determine if these differences also relate to humans, the scientists searched human breast cancer “knowledge bases” that tie the expression of patients’ tumor genes with their survival outcomes. They examined newly diagnosed women before they received chemotherapy or radiation. Women with gene expression levels similar to those of radiation-sensitive mice were less apt to survive after eight years. In comparison, women with expression levels similar to those of the resistant strain were more liable to survive the eight-year duration of the follow-up.

Then, gene expression analyses conducted a few hours after the end of low-dose exposure found alterations in many genes in the mammary tissue of cancer-sensitive mice. Large numbers of genes that control their immune system were suppressed, while genes that regulate pubertal mammary gland development were turned on by mistake. In cancer-resistant mice, these genes demonstrated only a small alteration in activity.

Analyses performed one month after exposure provided remarkable differences in the expression of a large collection of genes that control cell proliferation. The cancer-sensitive mice had up-regulated many genes associated with cell division and cell renewal. The cancer-resistant mice had downregulated these same genes below normal levels, which suggests they were able to activate tissue mechanisms that suppress cellular proliferation that can lead to cancer.

These disparities once more continued over to humans. Breast cancer patients whose renewal and cell division genes were upregulated, comparable to the cancer-sensitive mice that did not survive as long as patients in which the same genes were suppressed. The scientists are now engineering these gene expression signatures by studying large groups of women with breast cancer. They are also evaluating the processes by which these signatures control radiation sensitivity employing distinctive breast cell culture models developed at Berkeley Lab.

“This research opens promising opportunities for developing blood tests that predict a woman’s risk for breast cancer, and which identify women who are susceptible to the cancer effects of low-dose radiation exposures,” concluded Dr. Wyrobek.

Related Links:

Lawrence Berkeley National Laboratory



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80 (!!!!! 2038.9556884766): SELECT show_live FROM jos_com_show_setting LIMIT 1
81 (85.115432739258): SELECT show_live FROM jos_com_show_setting LIMIT 1
82 (49.829483032227): SELECT show_live FROM jos_com_show_setting LIMIT 1
83 (!!!!! 1178.0261993408): SELECT show_live FROM jos_com_show_setting LIMIT 1
84 (58.889389038086): SELECT show_live FROM jos_com_show_setting LIMIT 1
85 (58.889389038086): SELECT show_live FROM jos_com_show_setting LIMIT 1
86 (48.160552978516): SELECT show_live FROM jos_com_show_setting LIMIT 1
87 (!!!!! 1832.0083618164): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (226.97448730469): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (668.04885864258): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (88.930130004883): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (44.107437133789): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (395.05958557129): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (101.08947753906): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (209.09309387207): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (44.107437133789): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (!!!!! 3444.9100494385): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (122.0703125): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (50.067901611328): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 6965.8756256104): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
105 (145.91217041016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
106 (!!!!! 2851.9630432129): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (874.99618530273): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 1033.7829589844): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
109 (369.07196044922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
110 (!!!!! 1682.0430755615): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (674.96299743652): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (!!!!! 1734.9720001221): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (!!!!! 1006.1264038086): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (746.01173400879): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
115 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
116 (!!!!! 1608.8485717773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
117 (63.896179199219): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
118 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
119 (43.153762817383): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
120 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
121 (108.00361633301): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
122 (636.81602478027): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 47892.093658447): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (991.1060333252): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294743188 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294743188 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 20653.009414673): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (69.856643676758): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (609.8747253418): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (86.069107055664): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (179.76760864258): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (!!!!! 2176.04637146): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (511.88468933105): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (58.174133300781): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (53.167343139648): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (40.769577026367): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (!!!!! 3363.8477325439): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (530.00450134277): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (!!!!! 5777.12059021): SELECT name FROM jos_deeppockets WHERE id=211
138 (131.13021850586): SELECT name FROM jos_deeppockets WHERE id=211
139 (748.1575012207): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (!!!!! 1343.0118560791): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (114.91775512695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
142 (!!!!! 1256.9427490234): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
143 (!!!!! 20026.922225952): TRUNCATE TABLE jos_trademed_module
144 (!!!!! 6950.855255127): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (!!!!! 4734.992980957): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294743188 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (555.03845214844): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (263.92936706543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (385.99967956543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
149 (159.02519226074): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
150 (!!!!! 1577.1389007568): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (641.82281494141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
152 (148.05793762207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
153 (!!!!! 7704.9732208252): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294743188 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294743188 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (!!!!! 7922.887802124): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
155 (!!!!! 7977.9624938965): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
156 (!!!!! 7835.865020752): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (!!!!! 7993.9365386963): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
158 (!!!!! 7348.0606079102): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294743188 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294743188 AND published='1' LIMIT 1
159 (537.15705871582): select jos_twitters.link from jos_twitters where cat=10
160 (45.061111450195): select jos_facebook.link from jos_facebook where cat=10
161 (32.901763916016): select jos_google_plus.link from jos_google_plus where cat=10
162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10